[資料]製薬各社製品売上(世界):P-Z行
Medical Letter日本語版では、参考データとして市場データを調査しているが、 代表的な製薬企業のAnnual Reportから製品売上の部分を抜粋したものをここで掲載する。 ■個別製薬会社
■PDL BioPharma, Inc.[US]
- http://www.pdl.com/; (Nasdaq: PDLI) 旧Protein Design Labs, Inc. 1986年 Protein Design Labs, Incとして設立。 2006.1 社名変更 Protein Design Labs Becomes PDL BioPharma 2005.01 ESP Pharmaを買収。 (現金$300million +PDL株$175million) 2005.02 ESP社がRetavase商品化権をCentocorから取得した($110million+最大$45Mのmilestone) ことから、買収価額+$25M現金 ESP社は2002.5 Wyethから循環器系薬Cardene IV,Sectral, Tenex, ISMOを 取得して操業開始。 2003.6 Orphan Medical IncからIV Busulfanの全世界権 を獲得。 PDL社は、Humanized antibodiesを創製、2007年末、全市販9製品がライセンスされ、 うち8製品がライセンス料として収入を得ている。 ４０以上の抗体が臨床試験段階。 Genentech ... Herceptin, Xolair, Raptiva, Avastin, Lucentis Medimmune ... Synagis Wyeth ... Mylotarg Roche ... Zenapax /以上7製品の世界売上高(2004) $2.9 Billion Elan ... Tysabri (2004.11 FDA承認、2005.2にElan,Biogen-IDECが自主販売中 止；現在再レビュー待ち) ★パイプライン[2007末]●会社決算
製品 適応症 段階 提携先 備考 Daclizumab(Zenapax) Asthma Phase 2b準備 ― anti-IL2 receptor, 発売(Roche,急性腎移植拒否反応予防) Multiple sclerosis Phase 2準備 Biogen Idec Transplant maintenance Phase 2評価中 ― Volociximab (M200) Solid tumors Phase 2実施中 Biogen Idec anti-α5β1-integrin HuLuc63 Multiple myeloma Phase 1実施中 ― PDL192 Solid tumors Pre-IND ― Nuvion(R) (visilizumab) IV steroid-refractory
ulcerative colitisAugust 2007プログラム終了 ― anti-CD3 Cardene (nicardipine hydrochloride) Acute hypertension 市販済み→EKRに売却 ―
($ 000) 2007 2006 2005 2004 2003 2002 2001 2000 ●収入 Royalties $ 221,088 184,277 130,068 83,807 52,704 40,421 30,604 19,189 License他 37,837 64,792 28,395 12,217 13,982 5,952 13,796 21,220 計 258,925 249,069 158,463 96,024 66,686 46,373 44,400 40,409 ●原価経費 研究開発費 204,175 209,311 156,049 122,563 82,732 57,978 52,163 42,330 取得研開費 - - - � 85,993 - - - -<� 一般管理費 67,367 53,317 35,330 31,806 27,613 18,373 15,004 11,481 計 283,723 263,528 207,148 154,369 196,338 76,351 67,167 53,811 営業損失 (24,798) (14,459) (48,685) (58,345) (129,652) (29,978) (22,767) (13,402) 純利益 (21,061) (130,020) (166,577) (53,241) (129,814) (14,554) 2,647 647 従業員数 887 660 うち研究開発 529 171 販売 170 0 臨床・法制 - 113 製造 - 165 一般管理 188 103 品質管理 - 108
●PDL BioPharma, Inc.[US] ●Products Retavase -reteplase [Centocor,Inc.商標] Cardene IV -nicardipine HCl[ESP Pharma, Inc.商標] →Cardene IV(ニカルジピン塩酸塩) by EKR Therapeutics, Inc IV Busulfex -busulfan[ESP Pharma, Inc.商標] ●Pipeline ■Investors ●Annual Reports & SEC Filings 2007 Annual Report 10-K Annual Filings[2008.3.13] - [pdf] - [doc] - [xls] Report on Form 10-K for the fiscal year ended December 31, 2004[pdf,114p] ●News Bristol-Myers Squibb and PDL BioPharma Enter Global Alliance to Develop Novel Treatment for Multiple Myeloma[2008.8.19] - elotuzumab(現P1)およびPDL241(前臨床), another anti-CS1 antibody PDL BioPharma Declares $500 Million Special Cash Dividend and Announces Plan to Separate Its Biotechnology Operations From Its Antibody Humanization Royalty Assets[2008.4.10] - バイオ部門をスピンオフ。 抗体事業を残す。 Genmab and PDL BioPharma Close Sale of Antibody Manufacturing Facility[2008.3.18] - 抗体製造部門 PDL BioPharma Completes Sale of Cardiovascular Products to EKR Therapeutics[2008.3.10] - Cardene(R) I.V. (nicardipine HCl), Cardene SR(R) and 開発中の新製剤 Retavase(R) (reteplase) および開発中の ularitide; Otsuka Pharmaceutical and PDL BioPharma Close Sale of IV Busulfex[2008.3.10] - IV Busulfex(R) (busulfan)の全権。 Biogen Idec and PDL BioPharma License the Rights to Develop Volociximab in Ophthalmic Indications to Ophthotech[2008.1.8] - volociximab (M200)はBiogen Idec and PDL BioPharmaが癌領域で共同開発しているが。黄斑変性(AMD)等の眼科領域の全世界開発権をOphthotechにライセンス。 Otsuka Pharmaceutical Acquires Rights to IV Busulfex From PDL BioPharma[2007.12.17] - PDL BioPharma Announces Roche to Discontinue Co-Development of Daclizumab[2006.11.21] - 臓器移植維持療法の適応での共同開発中止 PDL BioPharma Announces Roche Discontinuation of Co-Development of Daclizumab in Asthma[2006.8.30] - 喘息の適応での共同開発中止 Protein Design Labs Becomes PDL BioPharma[2006.1.9] - 社名変更 Protein Design Labs Announces Exercise of Patent License Option by American Home Products [2000.5.18] - AHPに日本および他のアジア諸国について非独占ライセンス。 既に1999年に米国、欧州について非独占ライセンス。 MylotargはMay 17, 2000にFDAから迅速手続きで承認済み。
■Pfizer
2003.4.16 Pharmaciaを買収。($56 billion.) 2004.2.10 バイオ製薬企業Esperionを買収。($1.3 billion) 2005.9.14 Vicuron Pharmaceuticals Inc.を買収。($1.9 billion) *抗真菌剤Eraxis (anidulafungin) 抗生物質Zeven (dalbavancin)取得。 2005.4.12 バイオ製薬企業Idun Pharmaceuticals Inc.を買収。apoptosis治療薬を開発中。 2005.8.15 抗体技術を持つBioren Inc.を買収。 2005.9.30 Sanofi-AventisからCampto/Camptosar (irinotecan)の権利買収。($525 million) 2006.2 Sanofi-Aventisから吸入インスリンExuberaの権利買収。($1.4 billion) 2006.5 生物製剤企業Rinat Neurosciences Corp.買収。($880 million) CNS新薬を数種開発中。 2006.12 英ワクチンメーカーPowderMed Ltd.を買収。インフルエンザDNAワクチン、慢性ウイルス疾病ワクチン 2006.12.20 Consumer Healthcare事業を$16.6 billionでJohnson & Johnson に売却。 2008.1 Coley Pharmaceutical Group, Inc買収。specific emphasis on Toll-like receptorによる免疫療法 2008.1 CovX Research LLC買収。腫瘍・代謝領域のbiotherapeutics 2008.6 バイオ企業Encysive Pharmaceuticals Incを買収。 肺高血圧治療薬ThelinをEU等で販売 2008.6 Serenex, Inc.を買収。 a Heat Shock Protein 90を開発するバイオ会社 2009.1.26 Wyethを買収。 ■会社決算●事業別セグメント
($ milllion) 2009 2008 2007 2006 2005 2004 2003 2002 2001 売上高 48,296(-) 48,418(-) 48,371(+2) 47,405(-3)
旧51,298(-2)48,988
旧52,516(+17)41,787
旧44,73629,758 26,593 売上原価 8,112(-28) 11,239(+47) 7,640(+6)[15.8%] 7,232(+13)[15.3%]
旧8,525(+13)[16.6%]6,391[13.0%]
旧7,541(-21)[14.4%]9,589[21.4%] 販売・管理費 14.537(-7)[30.1%] 15,626(-)[32.3%] 15,589(+2)[32.2%] 15,313(-)[32.3%]
旧16,997(+1)[33.1%]15,304[31.2%]
旧16,903(+12)[32.2%]15,108[33.8%] 研究開発費 7,945(-2)[16.5%] 8,089(+6)[16.7%] 7,599(+5)[15.7%] 7,256(-3)[15.3%]
旧7,442(-3)[14.5%]7,513[15.3%]
旧7,684(+3)[14.6%]7,279
旧7,487[16.7%]5,153 4,896 取得研究開発費 633(+123)[1.3%] 283(-66)[0.6%] 835(-49)[1.7%] 1,652(+54)[3.5%] 1,071[2.2%] 5,052 - - 純利益 8,104(-) 8,144(-58) 19,337(+139)[40.0%] 8,085(-29)[17.1%] 11,361(+191)[23.2%] 3,910[8.7%] 9,126 7,788 従業員数 81,800 86,600 98,000 106,000 2006.12.20 Consumer Healthcare事業を$16.6 billionでJohnson & Johnson に売却。, ●製品別売上高
($ milllion) 2009 2008 2007 2006 2005 2004 2003 売上高 48,296(-) 48,418(-) 48,371(+2) 47,405(-3)
旧51,298(-2)48,988
旧52,516(+17)44,736 国内 20,435(-12) 23,153(-10) 25,822(+2) 24,745(-11)
旧26,664(-10)27,782
旧29,539(+10)26,795 国外 27,861(+10) 25,265(+12) 22,549(-) 22,660(+7)
旧24,634(+7)22,977(+28) 17,941 Pharmaceutical 44,174(-1) 44,424(-1) 45,083(+2) 44,269(-4) 46,121 39,425 国内 18,851(-13) 21,548(-12) 24,503(+4) 23,465(-12)
旧23,443(-12)26,606
旧26,583(+10)24,100 国外 25,323(+11) 22,876(+11) 20,580(-1) 20,804(+7)
旧20,841(+7)19,515
旧19,550(+28)15,325 Consumer Health - - 0
旧4,0440
旧3,8780
旧3,5162,949 国内 - - 0 0
旧1,941(+9)0
旧1,780(+8)1,649 国外 - - 0 0
旧1,937(+12)0
旧1,736(+34)1,300 Animal Health 2,825(+7) 2,639(+14) 2,311(+5) 2,206(+13) 1,953 1,598 国内 1,168(+3) 1,132(+10) 1,032(+4) 993(+13) 878(+19) 738 国外 1,657(+10) 1,507(+18) 1,279(+5) 1,213(+13) 1,075(+25) 860 その他 1,297(-4) 1,355(+39) 977(5) 930(+2) 914 764 国内 416(-12) 473(+65) 287(-) 287(-4) 298(-3) 308 国外 861(-) 882(+28) 690(+7) 643(+4) 616(+35) 456 [2008/2007年度報告] 特許切れ問題 2008年度通期では、ファイザーの公表収益は、ノルバスク、ジルテックおよびカンプトサール の独占権喪失による合計26億ドルの収益の減少にもかかわらず、前年度の484億ドルと 実質的には横ばいの483億ドルとなりました。 2006年および2007年にそれぞれ米国で独占権を喪失した製品、ゾロフト(2006.6)とノルバスクの 収益は同49％減少しました。 ノルバスク、カンプトサール（2008年2月）、ジルテック（2008年1月）が米国での独占権 を喪失するためで、ジルテックについては、一般用医薬品（OTC薬）が販売されることを 予想して当月で販売を終了する予定です。 Zithromaxは米国独占権喪失2005.11 リピトールはpravastatin (Pravachol)2006.4 /simvastatin (Zocor)2006.6の米国独占権喪失に 伴うジェネリックとの競合が続いた。 2007年度の米国でのリピトールの収益は8％減少しましたが、海外市場では9％増収となりました。益々価格に敏感になる環境でのブランド薬およびジェネリック薬の攻勢で、米国のスタチン市場は特に激しい競争が続いています。当社はこの攻勢に対して、リピトールの臨床面での強さを強調しながら、多岐にわたる統合的な取り組みで対応をしていく所存です。
($ milllion) 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 備考 ●循環器系・代謝系 17,922(-5) 18,853 19,871 18,732 17,412 16,171(+18) 13,664 - - - - - - ～米国 7,704(-18) 9,338(-16) 11,124 ～国外 10,218(+7) 9,515(+9) 8,747 旧[循環器系] - - - - - - 13,348(+15) 11,586[+12] 10,343[+17] 8,825 6,843 5,173 Lipitor 11,434(-8) 12,401(-2) 12,675(-2) 12,886(+6) 12,187(+12) 10,862(+18) 9,231(+16) 7,972(+24) 6,448[+28] 5,031[+33] 3,795 2,208 859 [atorvastatin]LDLコレステロール低下;米国特許失効2010 ～米国 5,667(-10) 6,324(-12) 7,195(-8) 7,849 ～国外 5,767(-5) 6,077(+11) 5,480(+9) 5,037 Norvasc 1,973(-12+) 2,244(-25) 3,001(-38) 4,866(+3) 4,706(+5) 4,463(+3) 4,336(+13) 3,846(+7) 3,581[+7] 3,362[+12] 2,991 2,541 2,188 [amlodipine]高血圧;米国独占権喪失2007.3 ～米国 64(-11) 72(-87) 603(-76) 2,500 ～国外 1,909(-12) 2,172(-10) 2,398(+1) 2,366 Chantix/Champix 700(-17) 846(-4) 883(+773) 101 - - [varenicline tartrate]禁煙;米国特許失効2018 ～米国 386(-21) 489(-30) 701(+593) 101 ～国外 314(-12) 357(+95) 182(*) - Caduet 548(-7) 589(+4) 568(+54) 370(+99) 185(+272) 50(-) [atorvastatin+amlodipine]高血圧、コレステロール低下 ～米国 394(-16) 469(-6) 497(+43) 349 ～国外 154(+28) 120(+68) 71(+244) 21 Cardura 457(-8) 499(-1) 506(-6) 538(-8) 586(-7) 628(+6) 594(+12) 531(-4) 551(-31) 795[+1] 784 679 618 [doxazosin]高血圧、前立腺肥大 ～米国 7(+25) 6(+4) 6(-16) 7 ～国外 450(-9) 493(-2) 500(-6) 531 Accupril/Accuretic - - 266(-10) 294(-56) 665(-6) 706(+6) 668(+11) 604[+9] 553[+8] 514 454 378 [quinapril]高血圧、心不全;ACE阻害剤 Procardia XL - - - - - - ? ? 218[-46] 311[-39] 510 714 822 nifedipine Revatio 450(+34) 336 [sildenafil]肺動脈高血圧 ～米国 293(+35) 217 ～国外 157(+33) 119 ●中枢神経系 6,005(+17) 5,152 6,038 6,391 8,093 7,378(+29) 5,726(+21) 4,740[+22] 3,883[+19] 3,271 2,694 2,066 ～米国 2,815(+17) 2,402(-34) 3,635 ～国外 3,190(+16) 2,750(+1) 2,403 Lyrica 2,840(+10) 2,573(+41) 1,829(+58) 1,156(+297) 291(-) 13(-) - - - - - - - [Pregabalin]てんかん/post-herpetic neuralgia/糖尿病性神経障害;米国特許失効2018 ～米国 1,504(+4) 1,448(+38) 1,048(+46) 717 ～国外 1,336(+19) 1,125(+44) 781(+78) 438 Geodon/Zeldox 1,002(-1) 1,007(+18) 854(+13) 758(+29) 589(+26) 467(+32) 353(+59) 222(+49) 150[-] --- --- --- --- [ziprasidone]統合失調症/双極性障害 ～米国 836(+2) 822(+17) 702(+11) 631 ～国外 166(-11) 185(+22) 152(+19) 127 Zoloft 516(-4) 539(+2) 531(-75) 2,110(-35) 3,256(-3) 3,361(+8) 3,118(+14) 2,742(+16) 2,365[+11] 2,140[+7] 1,997 1,803 1,479 [sertraline]うつ病/不安障害；;米国市場独占を2006.6に喪失。 ～米国 82(-31) 118(-24) 157(-91) 1,752 ～国外 434(+3) 421(+12) 374(+4) 358 Aricept 432(-10) 482(+20) 401(+12) 358(+4) 346(+12) 308(+22) 254(+25) 203(+29) 157 --- --- --- --- [donepezil HCl]アルツハイマー;米国特許失効2010 ～米国 -(+1) 1(+36) 1(+6) 1 ～国外 432(-10) 481(+20) 400(+12) 357 Neurontin - 387(-10) 431(-13) 496(-22) 639(-77) 2,723(+1) 2,702(+19) 2,269(+30) 1,751[+31] 1,334{+46] 913 514 292 [gabapentine] 抗てんかん/post-herpetic neuralgia ～米国 69(-9) 76(-16) 91 ～国外 318(-10) 355(-13) 405 Xanax,Xanax XR - 350(+8) 325(+3) 316(-23) 409(+8) 378(+59) 238(-) 0 - - - - - [Alprazolam]不安症/パニック障害 ～米国 59(-4) 61(-12) 70 ～国外 291(+10) 264(+7) 246 Relpax - 321(+2) 315(+10) 286(+23) 233(+38) 169(+99) 85(+435) 16 - - - - - [eletriptan HBr]片頭痛 ～米国 197(-3) 202(+9) 185 ～国外 124(+11) 113(+13) 101 ●リウマチ・痛み 3,096(+6) 2,914 2,711 2,386 5,212 3,046(+740) 363(-1) 365 - - - - ～米国 1,976(+5) 1,880(+6) 1,781 ～国外 1,120(+8) 1,034(+11) 930 Celebrex 2,383(-4) 2,489(+9) 2,290(+12) 2,039(+18) 1,730(-48) 3,302(+75) 1,883(-) 100(+31) 76 - - - - celecoxib;米国特許失効2014 ～米国 1,697(-7) 1,818(+6) 1,719(+9) 1,577 ～国外 686(+2) 671(+17) 571(+24) 462 Bextra - - - - -61(-) 1,286(+87) 687(-) 0 - - - - - valdecoxib ●感染症・呼吸器 3,931(+11) 3,552 3,474 ,770 4,718 ～米国 1,241(+10) 1,123(-8) 1,222 ～国外 2,690(+11) 2,499(+8) 2,252 旧[感染症] - - - - - 4,677(+29) 3,615(-1) 3,638(+3) 3,528[-3] 3,630 3,315 2,676 Zyvox 1,141(+2) 1,115(+18) 944(+21) 782(+27) 618(+33) 463(+156) 181(-) 0 - - - - - linezolid;米国特許失効2015 ～米国 634(-5) 670(+12) 600(+14) 527 ～国外 507(+14) 445(+30) 344(+35) 255 Vfend 798(+7) 743(+18) 632(+23) 515(+30) 397(+38) 287(+44) 200(+379) 42 - - - - - [voriconazole]真菌症 ～米国 250(+9) 230(+10) 210(+18) 178 ～国外 548(+7) 513(+21) 422(+25) 337 Zithromax 430(+0) 429(-2) 438(-31) 638(-69) 2,025(+9) 1,851(-8) 2,010(+33) 1,516(+1) 1,506[+9] 1,382[+6} 1,309 1,023 808 [azithromycin];米国市場独占を2005.11に喪失。 ～米国 18(+121) 8(-60) 24(-89) 210 ～国外 412(-2) 421(+1) 414(-3) 428 Diflucan - 373(-10) 415(-5) 435(-13) 498(-47) 945(-20) 1,176(+6) 1,112(+4) 1,066[+5] 1,014[+2] 989 904 870 [fluconazole]真菌症 ～米国 10(-22) 13(*) (17) ～国外 363(-10) 402(-11) 452 Viracept - - - - - - 259(-23) 336(-8) 364[-16] 436[-18] 530 530 228 [nelfinavir]抗HIV薬 Trovan - - - - - - - - 86 - 160 - ●泌尿器 3,204(+6) 3,010 2,809 2,684 2,634 2,457(+42) 1,735(+14) 1,518[+13] 1,344[+32] 1,016 773 ～米国 1,727(+6) 1,637(+3) 1,586 ～国外 1,477(+8) 1,373(+12) 1,223 Viagra 1,892(-2) 1,934(+10) 1,764(+6) 1,657(+1) 1,645(-2) 1,678(-11) 1,879(+8) 1,735(+14) 1,518[+13] 1,344[+32] 1,016 773 - [sildenafil]勃起不全;米国特許失効2012 ～米国 962(+7) 895(+13) 794(-) 796 ～国外 930(-11) 1,039(+7) 970(+13) 861 Detrol,Detrol LA 1,154(-5) 1,214(+2) 1,190(+8) 1,100(+11) 988(+9) 904(+66) 544(-) - - - - - - [tolterodine tartrate]過活動膀胱;米国特許失効2012 ～米国 811(-1) 821(-) 823(+7) 769 ～国外 343(-13) 393(+7) 367(+11) 331 ●癌 2,551(-3) 2,640 2,191 1,996 1,501 713(-) - - - - - - ～米国 537(-45) 972(+10) 887 ～国外 2,014(+21) 1,668(+28) 1,304 Sutent 964(+14) 847(+46) 581(+166) 219(-) - - [sunitinib]腎細胞癌、GIST(消化管間葉系腫瘍);米国発売2006;米国特許失効2021 ～米国 273(+7) 254(+7) 237(+42) 167 ～国外 691(+16) 593(+72) 344(+572) 52 Camptosar - 563(-42) 969(+7) 903(-) 910(+64) 554(+86) 299(-) - - - - - - [irinotecan]大腸癌;米国独占権喪失2008.2 ～米国 82(-85) 539(+10) 491 ～国外 481(+12) 430(+5) 412 Aromasin 483(+4) 465(+16) 401(+25) 320(+30) 247(+73) 143(+145) 58 [exemestane]乳癌 ～米国 163(+11) 146(+12) 131(+15) 113 ～国外 320(+0) 319(+18) 270(+31) 207 Pharmorubicin/Ellence - - - 312(-15) 367(+7) 344(+59) 216 - - - - - - [epirubicin]乳癌 ●眼科 1,777(+8) 1,643 1,461 1,373 1,227 770(-) - - - - - - ～米国 536(+1) 521(+8) 483 ～国外 1,241(+11) 1,122(+15) 978 Xalatan/Xalcom 1,737(+0) 1,745(+9) 1,604(+10) 1,453(+6) 1,372(+12) 1,227(+84) 623 - - - - - - latanoprost;米国特許失効2011 ～米国 576(+8) 532(+3) 521(+8) 483 ～国外 1,161(-4) 1,213(+12) 1,083(+12) 970 ●内分泌異常 1,153(+10) 1,052 985 1,049 925 550(-) - - - - - - ～米国 262(+4) 252(-2) 258 ～国外 891(+11) 800(+10) 727 Genotropin 887(-1) 898(+6) 843(+6) 795(-2) 808(+10) 736(+53) 481 - - - - - - ～米国 221(-5) 232(-) 232(+1) 230 ～国外 666(+0) 666(+9) 611(+8) 565 ●その他 2,284(-40) 3,819 4,169 3,823 3,677 3,110(+96) 1,584 - - - - - ～米国 753(-68) 2,360
旧2,555(-6)2,711 ～国外 1,531(+5) 1,459
旧1,459(-)1,458 旧[糖尿病] - - - - - - 316(+2) 308 412[-55] 916 273 234 Glucotrol XL - - - - - - 331(+11) 297(+5) 283[+1] 280[+9] 257 226 175 [Glipizide Extended Release]糖尿病 Rezulin - - - - - - - - 103 625 - 748 420 [troglitazone] [00.3.21中止] 旧[アレルギー] - - - - - 1,116(+12) 993(+41) 703[+29] 546 413 267 Zyrtec米国 - 129(-92) 1,541(-2) 1,569(+15) 1,362(+6) 1,287(-4) 1,338(+20) 1,115(+13) 990(+42) 699[+29] 541 407 260 cetrizine;米国独占権喪失2008.1;2008 OTC出現 Medrol - - - - - - 241(-) - - - - - - methylprednisolone ●Alliance Revenue 2,251(+26) 1,789(+30) 1,374 1,065
旧1,362(+6)722
旧1,287(-4)1,338 1,596(+16) 1,379(+19) 1,158[+74] 665 ? ? (Aricept,Macugen,Mirapex,Olmetec,Bextra,Celebrex,Spiriva and Rebif) ～米国 1,300(+22) 1,063(+30) 816 ～国外 951(+31) 726(+30) 558 ■人体用医薬品 45,448(+3) 44,174(-1) 44,424 45,083 44,269 46,121 39,631(+40) 28,283(+12) 25.240[+13] 22,567[+12] 20,155 ～米国 20,010(+6) 18,817(-13) 21,743(-11) 24,503 ～国外 25,438(+0) 25,357(+11) 22,876(+11) 20,580 ■動物薬 2,764(-2) 2,825(+7) 2,639 2,311 2,206 1,953 ■消費者保健 494 - ■栄養剤 191 - ■カプスゲル 740(-4) 767 ■その他 372(-30) 530
旧1,297(-4)1,355 977 930 914 ■総合計 50,009(+4) 48,296(-) 48,418 48,371 47,405 48,988 ～米国 21,749(+7) 20,401(-12) 23,348(-10) 25,822 ～国外 28,260(+1) 27,,895(+10) 25,265(+12) 22,549 ～米国 ～国外
●主要製品売り上げ[Wyeth]註）各国内・国外別データあり。Premarinグループは、別紙に製品別データ from 4Q 2004 Net Revenue Report -Product Net Sales Reports;個別製品売上高 ※Enbrel - 当初、北米はImmunex,Wyeth共販、他の全世界はWyethだったが、2001.12の AmgenによるImmnex買収により、北米Amgen,他の全世界Wyethとなった。 ※Alliance収入－Enbrel(北米)分の収入、Altace(ramipril;販売King)およびCypherステント(主成分sirolimus; J&J販売) 製品収益
($000) 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 備考 Effexor[旧W] 520,000(+) 3,927,856(+3.5) 3,793,904(+1.9) 3,722,052(+7.6) 3,458,835(+3.3) 3,347,369 2,711,706(+30.8) 2,072,316(+34.4) 1,542,016(+33.04) 1,159,088(+48.46%) 780,755 [venlafaxine]/[米特許]2008迄;海外名Efexor 米国内 455,000 2,686,868(+4.3) 2,577,062(+6.5) 2,419,514(+6.3) 2,275,121(+0.5) 2,264,199 1,864,780(+28.6) 1,449,975 米国外 65,000 1,240,988(+2.0) 1,216,842(-6.6) 1,302,538(+10.0) 1,183,714(+9.3) 1,083,170 846,926(+36.1) 622,429 2001.5 うつ病再発予防FDA承認、2001.Social anxiety disorder申請 Protonix米国内[旧W] 394,871(-79.3) 1,911,247(+6.5) 1,795,011(+6.5) 1,684,903(+5.9) 1,590,604 1,493,299(+39.5) 1,070,804(+90.8) 561,261(287.07) 145,002(+100) --- pantoprazole;PPI 米国のみ/[米特許]2010迄 Protonix Generic米国内[旧W] 411,569(-) - Prevnar[旧W] 287,000 2,715,507(+11.3) 2,439,056(+24.4) 1,961,325(+30.0) 1,508,259(+43.1) 1,053,629 945,646(+46.0) 647,528(-18.9) 798,210(+73.30) 460,586(+100) 00.1Q発売 Pneumococcal vaccine/[米特許]2007迄;海外名PREVENAR 米国内 144,000 1,180,062(+3.5) 1,140,462(+11.1) 1,026,433(+4.6) 981,334(+36.5) 718,772 769,340(+34.3) 572,969 米国外 143,000 1,535,445(+18.2) 1,298,594(+38.9) 934,892(+77.4) 526,925(+57.4) 334,857 176,306(+136.5) 74,559 Enbrel 米国外[旧W] 378,000 2,592,918(+26.8) 2,044,628(+36.3) 1,083,661(+38.4) 1,083,661(+59.4) 679,980 298,880(+88.2) 158,805(+69.2) 93,851(+149.33) 37,641(362.59) 8,137 etanercept*米加以外のみ,2002全$856m(+24)
Psoriatic arthritis (2002.1 FDA承認, EU 2001後半申請)/[米特許]2012迄ENBREL ALLIANCE REVENUE[旧W] 1,204,672(+20.5) 999,761 米国内 1,134,741(+20.6) 940,614 米国外 69,931(+18.2) 59,147 栄養剤[旧W] 1,633,901(+13.2) 1,443,034(+20.2) 1,200,814(+15.4) 1,040,922(+10.4) 943,255 857,576(+2.7) 834,725(+1.4) 823,536(+5.84) 690,794(-0.73) 695,848 *主に米国外 米国内 4,,352(+23.8) 3,514(-16.0) 4,184(-36.0) 6,538(-89.3) 61,053 63,026(+32.2) 47,672 米国外 1,629,549(+13.2) 1,439,520(+20.3) 1,196,630(+15.7) 1,034,384(+17.3) 882,202 794,550(+1.0) 787,053 Premarin群計[旧W] 213,000 1,070,401(+1.4) 1,055,337(+0.4) 1,050,860(+15.6) 908,887(+3.3) 880,181 1,275,347(-32.2) 1,879,860(-9.3) 2,073,525(+10.87) 1,870,221(+5.3) 1,776,144 HRT;結合estrogen 米国内 200,000 965,897(+1.8) 948,668(+1.2) 937,155(+20.8) 776,064(+7.9) 718,911 1,072,437(-33.5) 1,613,825(-10.1) 1,795,558 米国外 13,000 104,504(-2.0) 106,669(-6.2) 113,705(-14.4) 132,823(-17.6) 161,270 202,910(-23.7) 266,018(-4.3) 277,967 Premarin[旧W] 812,320(+0.0) 811,994(+21.7) 667,005(+1.2) 658,795 983,794(-20.9) 1,243,522(+4.9) 1,185,640 米国内 732,355(+0.0) 732,330(+26.8) 577,758(+3.1) 560,539 872,712(-21.0) 1,104,836(+5.6) 1,045,898 米国外 79,965(+0.4) 79,664(-10.7) 89,247(-9.2) 98,256 111,082(-19.9) 138,686(-0.8) 139,742 Prempro/phase[旧W] 243,017(+1.7) 238,866(-1.2) 241,882(+9.3) 221,386 291,553(-54.2) 636,321(-28.3) 887,885 /[米特許]2015迄 米国内 216,313(+5.6) 204,825(+3.3) 198,306(+25.2) 158,372 199,725(-60.8) 508,989(-32.1) 749,660 米国外 26,704(-21.6) 34,041(-21.9) 43,576(-30.8) 63,014 91,828(-27.9) 127,332(-7.9) 138,225 Zosyn/Tazocin[旧W] 184,000 1,264,036(+11.2) 1,137,193(+17.0) 971,994(+9.0) 891,573(+17.3) 760,288 638,671(57.3) 406,079(-7.7) 426,882(+11.02) 384,512(+16.1%) 315,701 [tazobactam+PIPC]/[米特許]2007迄;米国内ZOSYN国際TAZOCIN 米国内 138,000 701,105(+21.8) 575,775(+16.7) 493,467(+7.2) 460,159(+16.5) 355,313 355,313(+70.6) 208,247 米国外 46,000 562,931(+0.3) 561,418(+17.3) 478,527(+10.9) 431,414(+18.1) 365,334 283,358(+43.2) 197,830 OC[旧W] 385,969(-11.0) 433,854(-4.6) 454,908(-13.4) 525,326(-11.0) 590,138 589,190(+2.2) 576,299(-18.1) 562,578(-7.85) 610,163(-5.31%) 644,381 ORAL CONTRACEPTIVES (excluding Alesse) 米国内 42,459(-16.3) 50,740(-11.9) 57,597(-34.7) 88,149(-24.4) 116,600 138,285(-23.3) 180,278 米国外 343,510(-10.3) 383,114(-3.6) 397,311(-9.1) 437,177(-7.7) 473,538 450,905(+13.9) 396,022 ZOTON[旧W] 130,829(-65.2) 375,740(-16.1) 447,700 363,185(+17.4) 309,404(+8.9) 284,061(+21.47) 233,858(12.17) 208,469 lansoprazole*米国外のみ BeneFIX[旧W] 586,862(+35.6) 432,646(+21.0) 357,623(+4.2) 343,259(+13.8) 301,508 248,071(+13.2) 219,220(+3.0) 212,796(+18.19) 180,043(18.25) 152,255 Factor IX/[米特許]2011迄 米国内 262,818(-3.9) 273,541(-10.0) 304,005(+2.5) 296,554(+13.3) 261,787 218,397(+10.5) 197,605 米国外 324,044(+103.7) 159,105(+196.7) 53,618(+14.8) 46,705(+17.6) 39,721 29,674(+37.3) 21,615 Rapamune[旧W] 375,795(+3.0) 364,765(+8.3) 336,883(+12.2) 300,202(+15.9) 259,040 169,758(+30.8) 129,737(+84.9) 70,185(+165.35) 26,450(875.65) 2,711 sirolimus/[米特許]2009迄,延長2013可 米国内 190,876(+0.9) 189,134(+0.7) 187,763(+9.1) 172,047(+7.8) 159,666 101,726(+5.3) 96,602 米国外 184,919(+5.3) 175,631(+17.8) 149,120(+16.4) 128,155(+29.0) 99,374 68,032(+105.3) 33,135 ReFacto/XYNTHA[旧W] 47,000 363,254(+8.5) 334,857(+9.6) 305,626(+13.9) 268,411(+7.6) 249,379 224,173(+13.5) 197,549(+34.2) 147,259(+61.67) 91,085(+164.78) 34,400 Antihemophilic Factor/[米特許]2010迄 米国内 17,000 73,677(+0.3) 73,428(+12.9) 65,035(+17.4) 55,380(+26.6) 43,737 44,811(+2.4) 43,744 米国外 30,000 289,577(+10.8) 261,429(+8.7) 240,591(+12.9) 205,642(+3.6) 205,642 179,362(+16.6) 153,805 rhBMP-2[旧W] 389,621(+8.6) 358,886(+16.5) 307,940(+30.5) 236,291(+43.0) 165,279 58,100 66,500 /[米特許]2014迄;骨形成誘導 米国内 376,426(+7.4) 350,572(+15.4) 303,905(+29.4) 234,802(+42.8) 164,449 57,939 米国外 13,195(+58.7) 8,314(+106.0) 4,035(+171.0) 1,489(+79.4) 830 161 Tygacil [旧W] 216,184(+56.8) 137,906(+92.8) 71,516 10,004 [tigecycline]静注抗生物質；腹腔内感染または複雑性皮膚・皮膚組織感染症の治療薬として2005.3 FDA承認 米国内 132,531(+36.2) 97,277(+60.3) 60,680 9,905 米国外 83,653(+105.9) 40,629(+274.9) 10,836 99 Torisel[旧W] 122,117(+359.2) 26,593 [tensirolimus]腎細胞癌;米承認2007.5/欧承認2007.11 米国内 82,292(+216.2) 26,028 米国外 39,825(-) 565 Pristiq米国内[旧W] 66,512(-) - [desvenlafaxine]うつ病;米承認2008.2.29 小計 17,722,045(+4.8) 16,913,667
旧15,887,313(+13.2)14,166,949(+12.1) 12,626,269(+12.1) 11,268,358 米国内 8,707,056(-4.9) 9,158,062
旧8,191,420(+7.0)7,654,749(+8.7) 7,031,051(+8.3) 6,494,732 米国外 9,014,989(+16.2) 7,755,605
旧7,695,893(+20.6)6,512,200(+16.4) 5,595,218(+17.2) 4,773,626 ●他の医薬品 計[旧W] 1,303,385(-23.7) 1,708,316
旧1,440,474(-4.5)1,378,024(-10.4) 1,548,354(-18.8) 1,905,893 米国内 209,027(-60.3) 525,988
旧315,190(-0.3)316,198(-14.7) 380,704(-43.9) 678,564 米国外 1,094,358(-7.4) 1,182,328
旧1,125,284(-5.6)1,061,826(-9.0) 1,167,570(-4.9) 1,227,329 ALESSE[旧W] - - - - ? ? 140,834(+9.99) 128,046(37.44) 93,167 [norgestrel+EE]国際ブランド名=LOETTE Cordarone I.V.[旧W] - - - - ? 283,204(+5.0) 269,603(+32.71) 203,157(+5.67) 192,257 amiodarone ATIVAN[旧W] - - - 198,355 211,454(-2.7) 217,231(-6.6) 232,662(-5.46) 246,098(-3.21%) 254,258 lorazepam 抗不安 米国内 - - - 8,834 17,362(-59.8) 43,144 米国外 - - - 189,521 194,092(+11.5) 174,087 SYNVISC[旧W] - - 10,600 197,484 222,614(+4.8) 212,458(+12.8) 188,277(+5.02) 179,269(43.94) 124,547 Hylan G-F20 米国内 - - - 179,262 205,148(+5.9) 193,687 米国外 - - - 18,222 17,466(-6.5) 18,682 MINOCIN[旧W] - - - - 117,124(-4.1) 122,127(-17.02) 147,174(4.95) 140,234 minocycline FACTOR VIII[旧W] - - - - ? ? 129,195(+43.92) 89,767(-43.09) 157,727 米国のみ LODINE[旧W] - - - - ? ? ? 79,241(-49.7) 157,543 [etodolac] SONATA[旧W] - - - - - [Elanに譲渡] 88,818(+20.1) 73,951(+110.15) 35,190 zaleplon 睡眠障害 NEUMEGA[旧W] - - - - ? ? 29,139(-13.96) 33,866(-15.03) 39,856 oprelvekin MYLOTARG[旧W] - - - - ? ? 30,125(+49.19) 20,193(+100) --- [gemtuzumab ozogamicin]米国のみ;再発性・難治性骨髄性白血病の治療薬 Flumist[旧W] - - - - 15,249(-) - - - 2003発売 Influenza vaccine 米国のみ Generic[旧W] - - - 164,449 57,939 187,400 309,800 444,600 --- Meningitec[旧W] - - - - ? 90,100 78,610(-75.63) 322,575(+559.04) 48,946 *米国外のみ(髄膜炎菌グループC病用結合ワクチン) ZIAC/Zeta[旧W] - - - - ? 64,100 69,886(-75.37) 283,698(4.16%) 244,936 bisoprolol Alliance収入[旧W] 1,294,196(-3.4) 1,339,217(+16.8) 1,146,503(+45.2) 789,900 654,400 418,800 米国内 1,177,440(-1.8) 1,198,717(+17.4) 1,021,087(+41.2) 723,072 米国外 116,756(-16.9) 140,500(+12.0) 125,416(+87.8) 66,787 その他[旧W] - - - 1,509,900 1,660,500 2,128,700 ●Wyeth医薬合計[旧W] 19,025,430(+2.2) 18,621,983(+10.3) 16,884,190(+10.2) 15,321,126(+9.7) 13,964,110 12,622,700 11,733,300 米国内 8,916,083(-7.9) 9,684,050(+5.6) 9,169,664(+8.7) 8,432,922(+6.8) 7,896,368 米国外 10,109,347(+13.1) 8,937,933(+15.9) 7,714,526(+12.0) 6,888,204(+13.5) 6,067,742 Fort Dodge[旧W] 1,087,922(+4.4) 1,041,731(+11.3) 936,297(+6.3) 880,766(+5.3) 836,532 米国内 406,140(-9.0) 446,210(+7.9) 413,376(+5.1) 393,493(-0.5) 395,381 米国外 681,782(+14.5) 595,521(+13.9) 522,921(+7.3) 487,273(+10.5) 441,151 ●医薬品 合計[旧W] 19,663,714(+10.3) 17,820,487(+10.0) 16,201,892(+9.5) 14,800,642 米国内 10,130,260(+5.7) 9,583,040(+8.6) 8,826,415(+6.4) 8,291,749 米国外 9,533,454(+15.7) 8,237,447(+11.7) 7,375,477(+13.3) 6,508,893 ADVIL群[旧W] 673,269(-1.6) 684,099(+10.3) 620,164(+13.8) 636,440(+2.6) 620,101 604,300 米国内 483,915(-5.8) 513,812(+8.8) 472,216(+13.7) 473,360(-1.3) 479,455 米国外 189,354(+11.2) 170,287(+15.1) 147,948(+14.4) 163,080(+16.0) 140,646 CENTRUM[旧W] 727,965(+3.3) 704,895(+7.3) 657,052(+3.6) 633,978(+2.8) 616,632 545,600 米国内 323,666(-2.8) 332,842(-3.5) 344,859(+1.4) 339,954(-5.3) 358,973 米国外 404,299(+8.7) 372,053(+19.2) 312,193(+6.2) 294,024(+14.1) 257,659 ROBITUSSIN[旧W] 198,719(-9.8) 220,341(-2.3) 225,541(-10.9) 253,194(+6.4) 237,939 230,300 米国内 139,678(-15.9) 166,090(-8.4) 181,237(-14.6) 212,345(+5.2) 201,803 米国外 59,041(+8.8) 54,251(+22.5) 44,304(+8.5) 40,849(+13.0) 36,136 CALTRATE[旧W] 249,208(+10.3) 225,871(+15.8) 195,099(+3.1) 189,213(+5.7) 178,954 153,400 米国内 75,309(+3.1) 73,030(+13.3) 64,480(-7.5) 69,707(-3.4) 72,186 米国外 173,899(+13.8) 152,841(+17.0) 130,619(+9.3) 119,510(+11.9) 106,768 CHAPSTICK[旧W] 137,573(-1.6) 139,747(+9.2) 127,939(-4.8) 134,367(+9.0) 123,216 113,900 米国内 109,569(-2.7) 112,652(+3.2) 109,119(-4.7) 114,541(+9.5) 104,635 米国外 28,004(+3.4) 27,095(+44.0) 18,820(-5.1) 19,826(+6.7) 18,581 PREPARATION H[旧W] 111,735(+1.8) 109,712(+6.4) 103,096(-1.7) 104,853(+2.5) 102,303 92,300 米国内 87,308(+2.2) 85,454(+2.4) 83,415(+1.1) 82,538(+7.6) 76,717 米国外 24,427(+0.7) 24,258(+23.3) 19,681(-11.8) 22,315(-12.8) 25,586 ADVIL COLD & SINUS[旧W] 71,845(-2.5) 73,674(+20.8) 61,010(-33.4) 91,658 [] 米国内 29,948(-9.4) 33,039(+22.2) 27,047(-53.3) 57,905 米国外 41,897(+3.1) 40,635(+19.6) 33,963(+0.6) 33,753 THERMACARE[旧W] 26,470 - 米国内 20,510 - 米国外 5,960 - DIMETAPP[旧W] - - - 80,359(-8.5) 87,843 85,200 米国内 - - - 43,039(-12.8) 49,356 米国外 - - - 37,320(-3.0) 38,487 SOLGAR[旧W] - - - 58,472(-44.6) 105,462 105,100 米国内 - - - 28,089(-45.5) 51,506 米国外 - - - 30,383(-43.7) 53,956 ALAVERT[旧W] - - - 49,468(-11.6) 55,974 81,600 米国内 - - - 49,465(-11.6) 55,974 米国外 - - - 3(-) - 他の消費者向け保健製品[旧W] 523,772(-9.3) 577,745(+6.9) 540,267(-10.2) 413,550(-3.6) 428,962 441,500 米国内 122,498(-35.7) 190,505(+0.8) 189,003(-16.0) 104,349(-8.6) 114,154 米国外 401,274(+3.6) 387,240(+10.2) 351,264(-6.8) 309,201(-1.8) 314,808 ●消費者向け保健製品 計[旧W] 2,720,556(-0.6) 2,736,084(+8.1) 2,530,168(-0.9) 2,553,898(-0.1) 2,557,386 2,434,500 米国内 1,392,401(-7.6) 1,507,424(+2.4) 1,471,376(-3.0) 1,517,387(-3.0) 1,564,759 米国外 1,328,155(+8.1) 1,228,660(+16.0) 1,058,792(+2.1) 1,036,511(+4.4) 992,627 ●総合計[旧W] 22,833,908(+1.9) 22,399,798(+10.1) 20,350,655(+8.5) 18,755,790(+8.1) 17,358,028 米国内 10,714,624(-7.9) 11,637,684(+5.3) 11,054,416(+6.9) 10,343,802(+4.9) 9,856,507 米国外 12,119,284(+12.6) 10,762,114(+15.8) 9,296,239(+10.5) 8,411,988(+12.1) 7,501,520 米国内 米国外 (2)、(3)、(4)、(5)、(6) 脚注については文書の最後を参照 （2） 注記（3）および（5）に含まれる収益を除いた、全ての医療用医薬品の世界での収益を表す。 （3） 2005年以降に米国で上市された医療用医薬品の世界での収益を表す：チャンティックス／チャンピックス、 イラクシス、リリカ、マクジェン、レバチオ、セルゼントリー、スーテント、ジーマックス。 （4） 注記（5）に記載された2006年および2007年に米国で独占権を喪失した主要製品の収益を除いた世界での医療 用医薬品全収益。本報告書に添付された表を参照。 （5） 2006年および2007年に米国で独占権を喪失した医療用医薬品の世界での収益：ゾロフトおよびノルバスク （6） コンシューマー・ヘルスケア事業の譲渡にかかわる活動、カプスゲルおよびファイザー・センターソースを含む。 ★2008/2007/2006年度報告 Financial review p22/84p Recent FDA approvals follow:
（パーセントを除き単位は100万ドル） 第4四半期 通期 2007 2006 増減率 2007 2006 増減率 既存製品 (2) $10,010 $9,614 4％ $37,528 $36,504 3％ 新製品 (3) 1,103 569 94％ 3,559 1,603 122％ 既存製品と新製品 (4) の合計 11,113 10,183 9％ 41,087 38,107 8％ 独占権喪失製品 (5) 784 1,483 （47％） 3,532 6,976 （49％） 全医療用医薬品 11,897 11,666 2％ 44,619 45,083 （1％） アニマルヘルス 785 655 20％ 2,639 2,311 14％ その他 （6） 383 282 36％ 1,355 977 39％ 収益合計 $13,065 $12,603 4％ $48,613 $48,371 1％ Pending U.S. new drug applications (NDAs) and supplemental filings follow:
PRODUCT INDICATION DATE APPROVED 備考 Toviaz (fesoterodine) Treatment of overactive bladder October 2008 Zmax Community-acquired pneumonia-Pediatric filing October 2008 Selzentry (maraviroc) Treatment of human immuno- deficiency virus/acquired immune deficiency (HIV) in CCR5-tropic treatment-experienced patients August 2007 Lyrica Treatment of fibromyalgia June 2007 Fragmin Prevention of blood clots in patients with cancer May 2007 Lipitor Secondary prevention of cardiovascular (CV) events in patients with established coronary heart disease March 2007 Celebrex Juvenile rheumatoid arthritis December 2006 Aricept Treatment of severe Alzheimer's disease October 2006 Chantix(varenicline) Nicotine-receptor partial agonist for smoking cessation May 2006 Genotropin Treatment of long-term growth failure associated with Turner's syndrome April 2006 Geodon Treatment of schizophrenia and acute manic or mixed episodes associated with bipolar disorder－liquid oral suspension March 2006 Eraxis(anidulafungin) Treatment of candidemia and invasive candidiasis February 2006 Treatment of esophageal candidiasis February 2006 Exubera Inhaled form of insulin for use in adults with type 1 and type 2 diabetes January 2006 Sanofi Aventis社オリジン Sutent(sunitinib) Treatment of mRCC and refractory GIST January 2006 (a) The FDA granted priority review status to maraviroc in February [2008]
PRODUCT INDICATION DATE SUBMITTED 備考 Selzentry (maraviroc) HIV in treatment-na?ve patients December 2008 Geodon Maintenance treatment of bipolar mania December 2008 Geodon Treatment of bipolar disorders-Pediatric filing October 2008 Fablyn (lasofoxifene) Treatment of osteoporosis December 2007 Spiriva Respimat device for chronic obstructive pulmonary disease November 2007 Zmax Treatment of bacterial infections-sustained release-acute otitis media (AOM) and sinusitis-Pediatric filing November 2006 Vfend Treatment of fungal infections-Pediatric filing June 2005 Thelin Treatment of pulmonary arterial hypertension (PAH) May 2005 Fablyn (lasofoxifene) Treatment of osteoporosis December 2007 Spiriva Respimat device for chronic obstructive pulmonary disease November 2007 Zmax Treatment of bacterial infections- sustained release-Pediatric acute otitis media (AOM) filing November 2006 fesoterodine Treatment of overactive bladder March 2006 Vfend Treatment of fungal infections- Pediatric filing June 2005 dalbavancin(Zeven) Treatment of complicated skin/skin structure gram-positive bacterial infections December 2004 Vicuron社オリジン [2008]In September 2008, we announced that we would globally withdraw all dalbavancin marketing applications for the treatment of complicated skin and skin structure gram-positive bacterial infections in adults, including the U.S. NDA and the European marketing authorization application. We plan to conduct an additional Phase 3 clinical trial to support planned future regulatory submissions. A pediatric program with dalbavancin is also planned.
[2007]In December 2007, we received a third "approvable" letter from the FDA for dalbavancin. We and the third-party manufacturer are working with the FDA to respond to the requirements set forth in that letter.Lyrica(pregabalin) Treatment of fibromyalgia December 2006 Maraviroc
(UK-427857)(a)Treatment of human immuno-deficiency virus/acquired immune deficiency (HIV) in treatment-experienced patients December 2006 Zithromax(azithromycin extended release oral suspension) Bacterial infections-sustained release-Pediatric filing November 2006 Lipitor Secondary prevention of cardiovascular (CV) events in patients with established coronary heart disease (CHD) May 2006 Fesoterodine(b) Treatment of overactive bladder March 2006 Vfend Fungal infections-Pediatric filing June 2005
We received "not-approvable" letters from the FDA for Fablyn (lasofoxifene) for the prevention of post-menopausal osteoporosis in September 2005 and for the treatment of vaginal atrophy in January 2006. We submitted a new NDA for the treatment of osteoporosis in post-menopausal women in December 2007, including the three-year interim data from the Postmenopausal Evaluation And Risk-reduction with Lasofoxifene (PEARL) study in support of the new NDA. In September 2008, nine of the 13 members of an FDA advisory committee concluded that there is a population of women with post-menopausal osteoporosis for which the benefit of treatment with Fablyn is likely to outweigh the risks. In January 2009, we received a "complete response" letter from the FDA for the Fablyn submission. The FDA is seeking additional data and we are working with the FDA to determine the appropriate next steps regarding our application.
In September 2008, we received a "complete response" letter from the FDA for the Spiriva Respimat submission. The FDA is seeking additional data and we are working with the FDA to provide the additional information.In September 2007, we received an "approvable" letter from the FDA for Zmax that sets forth requirements to obtain approval for the pediatric AOM indication based on pharmacokinetic data. A supplemental filing for pediatric AOM and sinusitis remains under review.
In December 2005, we received an "approvable" letter from the FDA for our Vfend pediatric filing, which sets forth the additional requirements for approval. We have been systematically working through these requirements and addressing the FDA's concerns, including initiating an additional pharmacokinetics study in November 2008.
In June 2008, we completed the acquisition of Encysive, whose main product is Thelin. In June 2007, Encysive received a third "approvable" letter from the FDA for Thelin for the treatment of PAH. We began an additional Phase 3 clinical trial in patients with PAH during the fourth quarter of 2008 to address the concerns of the FDA regarding efficacy as reflected in that letter.
In September 2008, we announced that we would globally withdraw all dalbavancin marketing applications for the treatment of complicated skin and skin structure gram-positive bacterial infections in adults, including the U.S. NDA and the European marketing authorization application. We plan to conduct an additional Phase 3 clinical trial to support planned future regulatory submissions. A pediatric program with dalbavancin is also planned.[2007]
On September 28, 2007, we received an "approvable" letter from the FDA for Zmax that sets forth requirements to obtain approval for the AOM indication based on pharmacokinetic data. We plan to discuss these requirements with the FDA and seek an agreement on actions to address the FDA's comments.
We received an "approvable" letter from the FDA for fesoterodine for the treatment of overactive bladder in January 2007. Regulatory review of fesoterodine is progressing in the U.S. and fesoterodine was approved in the E.U. in April 2007. We are working with Schwarz Pharma, the licensor, to scale up manufacturing and identify manufacturing site alternatives. Launch is planned for mid-2008 in Europe and, subject to FDA approval, early 2009 in the U.S.
We received "not-approvable" letters from the FDA for Fablyn (lasofoxifene) for the prevention of post-menopausal osteoporosis in September 2005 and for the treatment of vaginal atrophy in January 2006. We submitted a new NDA for the treatment of osteoporosis in post-menopausal women in December 2007, including the three-year interim data from the Postmenopausal Evaluation And Risk-reduction with Lasofoxifene (PEARL) study in support of the new NDA.
In September 2005, we received a "not-approvable" letter for Dynastat (parecoxib), an injectable prodrug for valdecoxib for the treatment of acute pain. We have had discussions with the FDA regarding this letter, and we are considering plans to address the FDA's concerns.
Other regulatory approvals and filings in the E.U. and Japan:[2008] In December 2008, the Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion recommending that the European Commission grant marketing authorization for Fablyn (lasofoxifene) as a treatment for osteoporosis in post-menopausal women at increased risk of fracture in Europe. [2006] (a) Maraviroc has been granted accelerated review status in the E.U. (b) On February 23, 2007, the Committee for Medicinal Products for Human Use issued a positive opinion recommending that the European Commission grant marketing authorization for fesoterodine in Europe. [2007] Ongoing or planned clinical trials for additional uses and dosage forms for our products include:
PRODUCT DESCRIPTION OF EVENT DATE APPROVED DATE SUBMITTED 備考 Zithromac Approval in Japan for bacterial infections January 2009 - Celsentri (maraviroc) Application submitted in the E.U. for HIV in treatment-na?ve patients - January 2009 Approval in Japan for HIV in treatment-experienced patients December 2008 - Genotropin Approval in Japan for treatment of short stature/growth problems December 2008 - Geodon Application submitted in the E.U. for pediatric bipolar disorders - October 2008 rifabutin Approval in Japan for mycobacterium infection July 2008 - Macugen Approval in Japan for treatment of age-related macular degeneration July 2008 - Lyrica Application submitted in Japan for the treatment of pain associated with post-herpetic neuralgia - May 2008 Application submitted in the E.U. for the treatment of fibromyalgia - March 2008 Sutent Approval in Japan for treatment of mRCC and GIST April 2008 - Xalacom Application submitted in Japan for the treatment of glaucoma - February 2008 sildenafil Approval in Japan for treatment of PAH January 2008 - Fablyn (lasofoxifene)(a) Application submitted in the E.U. for the treatment of osteoporosis - January 2008 Chantix/Champix Approval in Japan as an aid to smoking cessation January 2008 - Caduet Application submitted in Japan for hypertension - November 2007 Celebrex Application submitted in Japan for treatment of lower-back pain - February 2007 Fablyn/(lasofoxifene) Application submitted in the E.U. for the treatment of osteoporosis - January 2008 Chantix/ Champix Approval in Japan as an aid to smoking cessation January 2008 - Spiriva Approval in the E.U. for Respimat device for chronic obstructive pulmonary disease November 2007 - Caduet Application submitted in Japan for hypertension - November 2007 Celsentri (maraviroc) Approval in the E.U. for the treatment of HIV in CCR5- tropic treatment- experienced patients September 2007 - Eraxis/Ecalta Approval in the E.U. for the treatment of invasive candidiasis in adult non- neutropenic patients September 2007 - Selera (Inspra) Approval in Japan for treatment of hypertension September 2007 - dalbavancin Application submitted in the E.U. for the treatment of skin and skin structure infections - July 2007 rifabutin Application submitted in Japan for Mycobacterium infection - June 2007 fesoterodine Approval in the E.U. for treatment of overactive bladder April 2007 - Macugen Application submitted in Japan for treatment of age-related macular degeneration - March 2007 Celebrex Approval in the E.U. for the treatment of ankylosing spondylitis February 2007 - Application submitted in Japan for treatment of lower- back pain - February 2007 Approval in Japan for treatment of osteoarthritis and rheumatoid arthritis January 2007 - sildenafil Application submitted in Japan for treatment of pulmonary arterial hypertension - February 2007 Somavert Approval in Japan for treatment of acromegaly January 2007 - Sutent Approval in the E.U. for mRCC as a first-line treatment January 2007 - Approval in the E.U. for GIST as a second-line treatment January 2007 - Application submitted in Japan for treatment of mRCC - December 2006 Application submitted in Japan for treatment of GIST - December 2006 Celebrex Approval in the E.U. for the treatment of ankylosing spondylitis February 2007 - Approval in Japan for treatment of rheumatoid arthritis January 2007 - Sutent Approval in the E.U. for mRCC as a first-line treatment January 2007 - Approval in the E.U. for GIST as a secondline treatment January 2007 - Approval in Canada for second-line treatment of mRCC August 2006 - Approval in Canada for second-line treatment of GIST May 2006 - Application submitted in Japan for mRCC - December 2006 Application submitted in Japan for GIST - December 2006 Application submitted in Canada for first-line treatment of mRCC - October 2006 Chantix/Champix Approval in Canada for smoking cessation January 2007 - Approval in the E.U. for smoking cessation September 2006 - Application submitted in Japan for smoking cessation - June 2006 Somavert Approval in Japan for acromegaly January 2007 - Maraviroc(a) Application submitted in the E.U. for treatment of HIV - December 2006 Lyrica Approval in the E.U. for the treatment of central neuropathic pain September 2006 - Approval in the E.U. for treatment of GAD in adults March 2006 - Spiriva Application submitted in the E.U.-Respimat device for chronic obstructive pulmonary disease - September 2006 Eraxis Application submitted in the E.U. for treatment of candidemia and candidiasis - September 2006 Fragmin Approval in Canada for treatment of medical thrombo-prophylaxis July 2006 - Neurontin Approval in Japan for treatment of epilepsy July 2006 - Genotropin Approval in Japan for hormone deficiency long-term replacement therapy in adults July 2006 - Aricept Application submitted in Canada for treatment of severe Alzheimer s disease - July 2006 Lipitor Approval in the E.U. for primary prevention of CV events in high coronary heart disease risk patients without established CHD May 2006 - Aromasin Approval in Canada for early breast cancer May 2006 - Vfend Approval in Canada for the powder form oral suspension May 2006 - Zyvox Approval in Japan for methicillin-resistant Staphylococcus aureus April 2006 - Zoloft Approval in Japan for treatment of depression and panic disorder April 2006 - Detrol/Detrol LA/Detrusitol Approval in Japan for treatment of overactive bladder April 2006 - Exubera Application submitted in Canada as an inhaled form of insulin for use in adults with type 1 and 2 diabetes - April 2006 Approval in the E.U. as an inhaled form of insulin for use in adults with type 1 and 2 diabetes January 2006 - Fesoterodine (b) Application submitted in the E.U. for treatment of over-active bladder - March 2006 Macugen(pegaptanib) Approval in E.U. for AMD January 2006 - Eyetech社オリジン Inspra Application submitted in Japan for hypertension - May 2002 [2008] New drug candidates in late-stage development include: axitinib, a multi-targeted kinase inhibitor for the treatment of renal cell carcinoma; Dimebon, a novel mitochondrial protectant and enhancer being developed in partnership with Medivation for the treatment of Alzheimer's disease; CP-751871, an anti-insulin-like growth factor receptor 1 (IGF1R) human monoclonal antibody for the treatment of non-small cell lung cancer; dalbavancin, for the treatment of skin and skin structure infections; tanezumab, an anti-nerve growth factor monoclonal antibody for the treatment of pain; and apixaban, for the prevention and treatment of venous thromboembolism and the prevention of stroke in patients with atrial fibrillation, which is being developed in collaboration with BMS.
PRODUCT INDICATION 備考 ●[2008] Celebrex Acute gouty arthritis Eraxis/Vfend Combination Aspergillosis fungal infections Lyrica Epilepsy monotherapy; post-operative pain; GAD; restless legs syndrome Macugen Diabetic macular edema Revatio Pediatric pulmonary arterial hypertension Sutent Breast cancer; colorectal cancer; non-small cell lung cancer; prostate cancer; liver cancer Zithromax/chloroquine Malaria ●[2007] Celebrex Acute gouty arthritis Eraxis/Vfend Combination Aspergillosis fungal infections Geodon/ Zeldox Bipolar relapse prevention; pediatric bipolar mania; adjunctive use in bipolar depression Lyrica Epilepsy monotherapy Macugen Diabetic macular edema Revatio Pediatric pulmonary arterial hypertension Selzentry/ Celsentri HIV in CCR5-tropic treatment-naive patients Sutent Breast cancer; colorectal cancer; non-small cell lung cancer; liver cancer Zithromax/ chloroquine Malaria ●[2006] Geodon/Zeldox Bipolar relapse prevention; bipolar pediatric Lyrica Generalized anxiety disorder; epilepsy monotherapy Revatio Pediatric pulmonary arterial hypertension Macugen(pegaptanib) Diabetic macular edema Eyetech社オリジン
In February 2009, we terminated the development programs for PD-332334, an alpha2delta ligand compound for the treatment of GAD, and esreboxetine, for the treatment of fibromyalgia, because it was considered unlikely that either compound would provide meaningful benefit to patients beyond the current standard of care.
In January 2009, we terminated the development program for axitinib, a multi-targeted kinase inhibitor, for the treatment of pancreatic cancer, after the review of interim data showed that the trial would not demonstrate superiority to the current standard of care.
In November 2008, we terminated the development program for CP-945,598, a cannabinoid-1 receptor antagonist for the treatment of obesity, based on changing regulatory perspectives on the benefit-risk profile of the cannabinoid-1 class and likely new regulatory requirements for approval.
In April 2008, we announced the discontinuation of a Phase 3 clinical trial of single-agent tremelimumab (CP-675,206), an anti-CTLA4 monoclonal antibody, in patients with advanced melanoma, after the review of interim data showed that the trial would not demonstrate superiority to standard chemotherapy. Additional product-related programs are in various stages of discovery and development.
[2006年度報告]主要製品戦略 p37/175p 10-K Annual report[Section 13 and 15(d), not S-K Item 405][2007.3.1; pdf,33p] -[Exhibits,pdf,175p] . Lipitor, for the treatment of elevated LDL-cholesterol levels in the blood, is the most widely used treatment for lowering cholesterol and the best-selling pharmaceutical product of any kind in the world, reaching about $12.9 billion in worldwide sales in 2006, an increase of 6% compared to 2005. In the U.S., sales of $7.8 billion represent growth of 6% over 2005. Internationally, Lipitor sales in 2006 increased 5% compared to 2005. The growth in Lipitor revenues was driven by a combination of factors, including dosage-form escalation and pricing (including a favorable development in a pricing dispute in the U.S.), as well as changes in rebate patterns. We continue to see aggressive competition from branded and generic agents, particularly when additional generic agents became available in the U.S. near the end of 2006. Lipitor began to face competition in the U.S. from generic pravastatin (Pravachol) in April 2006 and generic simvastatin (Zocor) in June 2006, as well as other competitive pressures. These launches have impacted the dynamics of the statin market and increased pressure on Lipitor. In October 2006, we launched a new advertising campaign for Lipitor that highlights its strong benefit profile, particularly its benefit in reducing the risk of heart attack and stroke in patients with multiple risk factors for heart disease. This builds on the consumer advertising that was implemented in April 2006. Scientific data continue to reinforce the trend toward the use of higher dosages of statins for greater cholesterol reduction. See Notes to Consolidated Financial Statements.Note 19. Legal Proceedings and Contingencies for a discussion of recent developments with respect to certain patent litigation relating to Lipitor. ※アトルバスタチン(リピトール)の重要な新展開-米国に次ぎ欧州において新たに心臓発作、脳卒中発症予防の適応症取得[2006.6.20] リピトール心疾患患者を対象に新たに5つの適応症をFDAが承認[2007.3.15] . Norvasc is the world’s most-prescribed branded medicine for treating hypertension. Norvasc maintains exclusivity in many major markets globally, including the U.S., Japan, Canada and Australia, but has experienced patent expirations in many E.U. countries. Norvasc sales in 2006 increased 3% compared to 2005. See Notes to Consolidated Financial Statements.Note 19. Legal Proceedings and Contingencies for a discussion of recent developments with respect to certain patent litigation relating to Norvasc. . Caduet, single-pill therapy combining Norvasc and Lipitor, recorded worldwide revenues of $370 million with a growth rate of 99% in 2006 compared to 2005. Caduet was launched in the U.S. in May 2004 and continues to grow at significantly higher rates than the overall U.S. cardiovascular market. This was largely driven by a more focused message platform and a highly targeted consumer campaign. Caduet is available in more than 15 other countries. Caduet has now received approvals in 58 markets with drug applications pending in nine additional markets and applications planned in 13 other countries. In early 2007, Caduet is expected to be launched in Spain and Taiwan. See Notes to Consolidated Financial Statements.Note 19. Legal Proceedings and Contingencies for a discussion of recent developments with respect to certain patent litigation relating to Caduet. [2006年度報告]特許問題 p141/175p 10-K Annual report[Section 13 and 15(d), not S-K Item 405][2007.3.1; pdf,33p] -[Exhibits,pdf,175p] amlodipine (Norvasc), atorvastatin (Lipitor), tolterodine (Detrol), celecoxib (Celebrex) and atorvastatin/amlodipine combination (Caduet).に関して発生。 ・Norvasc (amlodipine) Between 2002 and 2005, we brought patent infringement suits in various federal courts against several manufacturers that have filed abbreviated new drug applications with the FDA seeking to market a generic version of amlodipine besylate, which is the salt form contained in Norvasc. Our patent for amlodipine besylate is being challenged in all of the suits. While the basic patent for amlodipine also was challenged in certain of the suits, that patent expired in 2006 and those challenges did not go to trial. In the first of these actions to go to trial, in January 2006 the U.S. District Court for the Northern District of Illinois held that our amlodipine besylate patent is valid and infringed by the generic manufacturer Torpharm/Apotex Inc.’s product. The court issued an injunction prohibiting Torpharm/Apotex from marketing its generic amlodipine besylate product before the expiration of our amlodipine besylate patent (including the additional six-month pediatric exclusivity period) in September 2007. In February 2006, Torpharm/Apotex appealed the decision to the U.S. Court of Appeals for the Federal Circuit. A hearing on the appeal was held in November 2006; the appeals court has not yet handed down its decision. Similarly, in the second of these actions to go to trial, in August 2006 the U.S. District Court for the Middle District of North Carolina held that our amlodipine besylate patent is valid and infringed by generic manufacturer Synthon Pharmaceuticals, Inc.’s product. The court issued an injunction prohibiting Synthon from marketing its generic amlodipine besylate product before September 2007. In September 2006, Synthon appealed the decision to the U.S. Court of Appeals for the Federal Circuit. This appeal has not yet been heard. Finally, in the third of these actions to go to trial, in February 2007 the U.S. District Court for the Western District of Pennsylvania held that our amlodipine besylate patent is valid and infringed by generic manufacturer Mylan Pharmaceuticals, Inc.’s product. The court issued an injunction prohibiting Mylan from marketing its generic amlodipine besylate product before September 2007. In February 2007, Mylan appealed the decision to the U.S. Court of Appeals for the Federal Circuit. This appeal has not yet been heard. Separately, in November 2005 Synthon IP filed an action against us in the U.S. District Court for the Eastern District of Virginia alleging that our sales of Norvasc and Caduet infringe Synthon’s patent relating to the manufacture of amlodipine. In August 2006, the jury held that Synthon’s patent is invalid and is not infringed by our sales of Norvasc and Caduet. The court’s final judgment, which has not yet been handed down, will be subject to possible appeal. ・Lipitor (atorvastatin) The generic manufacturer Ranbaxy Laboratories Limited filed an abbreviated new drug application with the FDA for atorvastatin (Lipitor) in 2002 and amended the application in 2003 to allege that its product would not infringe our basic product patent for atorvastatin. Shortly thereafter, Ranbaxy also asserted that our patent covering the active enantiomeric form of the drug is invalid. Our basic patent for Lipitor, including the additional six-month pediatric exclusivity period, expires in March 2010. Our enantiomer patent, including the six-month pediatric exclusivity period, expires in June 2011. In 2003, we filed suit in the U.S. District Court for the District of Delaware against Ranbaxy for infringement of both our basic product patent and our patent covering the active enantiomeric form of the drug. In late 2005, the District Court held that both patents are valid and infringed by Ranbaxy’s generic atorvastatin product. In August 2006, a panel of the U.S. Court of Appeals for the Federal Circuit affirmed the District Court’s decision with respect to our basic product patent. In August 2006, Ranbaxy filed a request for a review of that decision by the full U.S. Court of Appeals for the Federal Circuit, and that request was denied in October 2006. In January 2007, Ranbaxy filed a request for a review of the panel’s decision by the U.S. Supreme Court; the court has not yet ruled on Ranbaxy’s request. The panel also ruled that one of the claims of our enantiomer patent is invalid on technical grounds. The U.S. Patent and Trademark Office has a process for correcting technical defects in patents. In January 2007, we filed a reissue application with the Patent Office seeking to correct the technical defect in our enantiomer patent. As noted, our patent rights to Lipitor also are being challenged in various other countries. In October 2005, in an action brought by Ranbaxy, the United Kingdom’s High Court of Justice upheld our basic U.K. patent for Lipitor, which expires in November 2011, but ruled that a second patent covering the calcium salt of atorvastatin, which expires in July 2010, is invalid. In June 2006, the United Kingdom’s Court of Appeal affirmed the lower court’s decision. The ruling by the Court of Appeal prohibits Ranbaxy from marketing a generic version of atorvastatin in the U.K. before the expiration of our basic patent in November 2011. In December 2006, the House of Lords denied both parties’ appeals of the Court of Appeal ruling. In Canada, our patent rights to Lipitor are being challenged by a number of generic manufacturers. In January 2007, the Canadian Federal Court in Toronto held that our basic Canadian patent for Lipitor, which expires in May 2007, would be infringed by Ranbaxy’s generic atorvastatin product. However, the court denied our application to block approval of Ranbaxy’s generic product based on a second patent covering the calcium salt of atorvastatin, which expires in July 2010. In February 2007, we appealed the ruling on the calcium salt patent to the Federal Court of Appeal of Canada. The ruling on the calcium salt patent has no immediate commercial impact because Ranbaxy is subject to other pending patent litigation with Pfizer with respect to atorvastatin. ※ファイザー社、英国高等法院で「リピトール」の基本特許をめぐる裁判に勝訴―「リピトール」の特許は英国で2011年まで後発品との競争から保護される―[2005.10.18] ファイザー、カナダの「リピトール」訴訟で痛手[2006.10.14] Canadian court blocks generic version of Pfizer's drug - Apr. 30, 2007 ・Detrol (tolterodine) In March 2004, we brought a patent infringement suit in the U.S. District Court for the District of New Jersey against a generic manufacturer that had filed an abbreviated new drug application with the FDA seeking approval to market tolterodine (Detrol). In January 2007, the generic manufacturer withdrew its challenge to our patent, and the patent infringement suit was dismissed. At about the same time in January 2007, a company affiliated with the generic manufacturer amended its previously filed abbreviated new drug application for tolterodine to challenge our tolterodine patent, and we brought a patent infringement action against that company in the U.S. District Court for the District of New Jersey. ・Celebrex (celecoxib) 2004.1 GEメーカーがFDAにANDA申請。 当社は2004.2に裁判所に提訴。 ・Caduet (atorvastatin/amlodipine combination) In January 2007, a generic manufacturer notified us that it had filed an abbreviated new drug application with the FDA seeking approval to market a generic version of Caduet. We intend to file suit against the generic manufacturer shortly asserting infringement of our patents relating to atorvastatin and to the atorvastatin/amlodipine combination. ・Exubera In August 2006, Novo Nordisk filed an action against us in the U.S. District Court for the Southern District of New York alleging that our sales of Exubera infringe Novo Nordisk’s patents relating to inhaled insulin and methods of administration of inhaled insulin and seeking monetary and permanent injunctive relief. In December 2006, the court denied Novo Nordisk’s motion for a preliminary injunction that would have barred the sale of Exubera during the pendency of this litigation. ★PL関連 ・糖尿病薬Rezulin(troglitazone) --- $269 millionの補償請求する健康保険業者らとの訴訟が継続。 ・子会社Quigley Company, Inc. (Quigley)のアスベスト訴訟に関しては、2004Q3迄に$369 million before-tax ($229 million after-tax)を支払ってきた。 2004.10に某保険会社との合意に従って、当社は１０年以上にわたって合計$406 millionの支払う。 ・Viagraにより視力喪失したとの訴訟は､継続。2006.1 連邦裁判所は、各地裁に差し戻し。 ・Zoloftによる自殺訴訟は継続。 ★消費者・商法関連 ・Neurontin訴訟は、2004.10 連邦裁判所は、各地裁に差し戻し。 ※本剤については、Warner Lambert社が販売していた1996年に内部告発と提訴をきっかけに、全米各地で団体訴訟が発生。 これは同社MRが承認外の１１の適応症に効くと病医院医師に宣伝し、Off-Label使用を勧めていたことに関するもの。 誇 大宣伝等のAntitrust法違反で政府調査が実施され、この結果、ファィザー社は昨2003年末に４億ドル以上の巨額の引当金を計上している。 ・Lipitorの誇大宣伝に伴う損害賠償訴訟 2005.9 米国連邦裁判所に提訴。 ２件は取り下げ。 残る１件は係争中。 これ以外にも各種係争あり。 ■感染症 ★Zyvox (linezolid);米国特許失効2015【2008】Zyvox is for the treatment of hospital-acquired pneumonia and complicated skin infections due to drug-resistant bacteria known as Methicillan-Resistant Staphylococcus Aureus. Zyvox is available in intravenous, tablet and oral-suspension formulations.Zyvox is the world's best-selling branded agent for the treatment of certain serious Gram-positive pathogens, including Methicillin-Resistant Staphylococcus-Aureus (MRSA). MRSA remains a serious and growing threat in hospitals and the community. Zyvox is an excellent first-line choice for the treatment of adults and children with complicated skin and skin structure infections and nosocomial pneumonia due to known or suspected MRSA. Zyvox is the only FDA approved agent for MRSA that offers intravenous and oral formulations for these indications. Its unique mechanism of action minimizes the potential for cross-resistance. To date, more than three million patients have been treated worldwide. Zyvox worldwide sales grew 18% to $1.1 billion in 2008.
【2007】Zyvox is for the treatment of bacterial infections, which increasingly are caused by drug-resistant bacteria, and the treatment of diabetic foot infections. Zyvox is available in intravenous, tablet and oral-suspension formulations.
Zyvox is the world's best-selling branded medicine for serious gram-positive infections in adults and children, which increasingly are caused by drug-resistant bacteria in hospitals and more recently, in the community setting. Zyvox is an appropriate first-line therapy for patients with serious complicated skin and skin structure infections or nosocomial pneumonia known or suspected to be caused by gram-positive pathogens, including Methicillin-resistant Staphylococcus aureus (MSRA) infection, with the flexibility of an intravenous and oral regimen. Zyvox works with a unique mechanism of action, which minimizes the potential for cross-resistance with other antibiotic classes and thus has the potential to effectively treat MRSA infection despite growing resistance to other important antibiotics. Worldwide sales of Zyvox grew 21% to $944 million in 2007.
★Zithromax [azithromycin];米国市場独占を2005.11に喪失。 【2007】Zithromax/Zmax, for the treatment of bacterial infections, experienced a 31% decline in worldwide revenues in 2007 compared to 2006, reflecting the expiration of Zithromax's composition-of-matter patent in the U.S. in November 2005 and the end of Pfizer's active sales promotion in July 2005.
★Selzentry/Celsentri (maraviroc) FDA承認Aug 2007
[2007]
Selzentry/Celsentri (maraviroc) is the first in a new class of oral HIV medicines in more than a decade known as CCR5 antagonists. CCR5 antagonists work by blocking the CCR5 co-receptor, the virus' predominant entry route into T-cells. Selzentry/Celsentri stops the R5 virus on the outside surface of the cells before it enters, rather than fighting the virus inside, as do all other classes of oral HIV medicines. Selzentry/Celsentri was approved in the U.S. in August 2007 and in Europe in September 2007, and is indicated for combination anti-retroviral treatment of treatment-experienced adults infected with only CCR5-tropic HIV-1 detectable, who have evidence of viral replication and have HIV-1 strains resistant to multiple anti-retroviral agents. A diagnostic test confirms whether a patient is infected with CCR5-tropic HIV-1, which is also known as "R5-virus."
★Vfend[voriconazole]真菌症【2008】Vfend is a treatment that can be administered orally or intravenously for certain serious and potentially fatal fungal infections, for the treatment of esophageal candidiasis and for the treatment of certain blood stream infections in non-neutropenic patients (those without low white blood cell counts). It is also available in an oral-suspension formulation suitable for patients unable to swallow the tablet form.
★Eraxis[]抗真菌剤【2008】Eraxis is an injectable, antifungal antibiotic used to treat serious candida (yeast) infections in the blood, stomach or esophagus. Eraxis became available to patients in the U.S. in 2006 and in Europe in 2008.
★Selzentry/Celsentri[] HIV薬【2008】Selzentry/Celsentri is the first in a new class of oral HIV medicines in more than a decade known as CCR5 antagonists. CCR5 antagonists work by blocking the CCR5 co-receptor, the virus' predominant entry route into T-cells. Selzentry/Celsentri stops the R5 virus on the outside surface of the cells before it enters, rather than fighting the virus inside, as do all other classes of oral HIV medicines. Selzentry/Celsentri was approved in the U.S. and in Europe in 2007 and in Japan in 2008 and is indicated for combination anti- retroviral treatment of treatment-experienced adults infected with only CCR5-tropic HIV-1 detectable, who have evidence of viral replication and have HIV-1 strains resistant to multiple anti-retroviral agents.Selzentry/Celsentri (maraviroc tablets), a CCR5 antagonist, is the first in a new class of oral HIV medicines in more than a decade known as CCR5 antagonists. CCR5 antagonists work by blocking the CCR5 co-receptor, the virus' predominant entry route into T-cells. Selzentry/Celsentri stops the R5 virus on the outside surface of the cells before it enters, rather than fighting the virus inside, as do all other classes of oral HIV medicines. Selzentry/Celsentri was approved in the U.S. and in Europe in 2007 and in Japan in 2008, and is indicated for combination anti-retroviral treatment of treatment-experienced adults infected with only CCR5-tropic HIV-1, who have evidence of viral replication and have HIV-1 strains resistant to multiple anti-retroviral agents. A diagnostic test confirms whether a patient is infected with CCR5-tropic HIV-1, which is also known as "R5-virus." We accelerated the Selzentry/Celsentri development program to make it available to patients in need. Performance has been driven by increased access and reimbursement of tropism testing, targeted promotion and combination therapy with new agents.
■泌尿器 ★Viagra[sildenafil]勃起不全;米国特許失効2012【2008】Viagra remains the leading treatment for erectile dysfunction (ED) and one of the world's most recognized pharmaceutical brands.
★Detrol,Detrol LA[tolterodine tartrate]過活動膀胱;米国特許失効2012【2008】Detrol is the world's leading product for the treatment of overactive bladder. Detrol LA is an extended-release formulation of this medicine, taken once a day.Detrol/Detrol LA, a muscarinic receptor antagonist, is the most prescribed branded medicine worldwide for overactive bladder. Detrol LA is an extended-release formulation taken once a day. Detrol/Detrol LA worldwide revenues grew 2% to $1.2 billion in 2008, compared to 2007.
★Toviaz[fesoterodine]過活動膀胱【2008】Toviaz is Pfizer's newest offering for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and frequency. It is available in two once-daily doses, providing physicians and patients with the ability to optimize treatment through flexible dosing. Toviaz was approved in Europe in April 2007 and in the U.S. in October 2008. It is marketed in 15 European countries and is expected to launch in the U.S. in the first half of 2009.
■癌 ★Sutent[sunitinib]腎細胞癌、GIST(消化管間葉系腫瘍);米国発売2006;米国特許失効2021【2008】Sutent is an oral multi-kinase inhibitor that combines anti-angiogenic and anti-tumor activity to inhibit the blood supply to tumors. Sutent was approved by the FDA and launched in the U.S. in January 2006 for advanced renal cell carcinoma, including metastatic renal cell carcinoma (mRCC), and gastrointestinal stromal tumors (GIST) after disease progression on or intolerance to imatinib mesylate. In January 2007, Sutent received full marketing authorization and extension of the indication to first-line treatment of advanced and/or metastatic renal cell carcinoma, as well as approval as a second-line treatment of GIST, in the EU. In Japan, it was approved in April 2008 for the treatment of GIST, after failure of imatinib treatment due to resistance, and for renal cell carcinoma not indicated for curative resection and mRCC.Sutent, for the treatment of advanced renal cell carcinoma, including metastatic renal cell carcinoma, and gastrointestinal stromal tumors (GIST) after disease progression on, or intolerance to, imatinib mesylate, was launched in the U.S. in January 2006. It has now been launched in all major markets, including Japan, where it was approved in April 2008 for the treatment of GIST, after failure of imatinib treatment due to resistance, and for renal cell carcinoma not indicated for curative resection and mRCC. Sutent recorded worldwide revenues of $847 million in 2008, an increase of 46% compared to 2007. We continue to drive growth in the U.S. and internationally, supported by cost-effectiveness data and efficacy data in first-line mRCC-including 2-year survival data, which represents the first time overall survival of two years has been seen in the treatment of advanced kidney cancer, as well as through strong promotional efforts and the promotion of access and health care coverage. As of September 30, 2008, Sutent was the best-selling medicine in the world for the treatment of first-line mRCC.
★Camptosar[irinotecan]大腸癌;米国独占権喪失2008.2【2008】Camptosar, which is marketed under the name Campto in many countries outside the U.S., is indicated as first-line therapy for metastatic colorectal cancer in combination with 5-fluorouracil and leucovorin. The U.S. basic patent for Camptosar expired in February 2008.Camptosar, indicated as first-line therapy for metastatic colorectal cancer in combination with 5-fluorouracil and leucovorin, lost exclusivity in the U.S. in February 2008. It is also indicated for patients in whom metastatic colorectal cancer has recurred or progressed following initial fluorouracil-based therapy. Camptosar is for intravenous use only. Camptosar worldwide revenues decreased 42% to $563 million in 2008, compared to 2007.
★Aromasin[exemestane]乳癌【2008】
■眼科薬 ★Xalatan/Xalcom[latanoprost];米国特許失効2011【2008】Xalatan/Xalacom is the world's leading branded agent to reduce elevated eye pressure in patients with open-angle glaucoma or ocular hypertension. Xalacom , a fixed combination of Xalatan and the beta blocker timolol, is currently available outside the U.S.Xalatan, a prostaglandin, is the world's leading branded agent to reduce elevated eye pressure in patients with open-angle glaucoma or ocular hypertension. Xalatan's proven clinical benefits and studies demonstrating long-term safety should support the continued growth of this important medicine. Xalacom, a fixed combination prostaglandin (Xalatan) and beta blocker (timolol), is available outside the U.S. Xalatan/Xalacom worldwide revenues grew 9% in 2008, compared to 2007.
■内分泌 ★Genotropin【2008】Genotropin is the world's leading human growth hormone. It is prescribed for children for the treatments of short stature with growth hormone deficiency, Prader-Willi Syndrome, Turner Syndrome, Small for Gestational Age Syndrome, Idiopathic Short Stature (in the U.S. only) and Chronic Renal Insufficiency (outside the U.S.) as well as for adults with growth hormone deficiency.Genotropin, the world's leading human growth hormone, is used in children for the treatment of short stature with growth hormone deficiency, Prader-Willi Syndrome, Turner Syndrome, Small for Gestational Age Syndrome, Idiopathic Short Stature (in the U.S. only) and Chronic Renal Insufficiency (outside the U.S. only), as well as in adults with growth hormone deficiency. Genotropin worldwide revenues grew 6% in 2008 to $898 million, compared to 2007, driven by its broad platform of innovative injection-delivery devices.
■循環器 ★Lipitor (atorvastatin)LDLコレステロール低下;米国特許失効2010【2008】Lipitor, for the treatment of elevated LDL-cholesterol levels in the blood, is the most widely used prescription treatment for lowering cholesterol and the best-selling pharmaceutical product of any kind in the world. Lipitor recorded worldwide revenues of $12.4 billion in 2008, a decrease of 2% compared to 2007 despite the favorable impact of foreign exchange, which increased revenues by approximately $310 million, or 2%. In the U.S., revenues of $6.3 billion in 2008 declined 12% compared to 2007. Internationally, Lipitor revenues in 2008 increased 11% compared to 2007, with 6% due to the favorable impact of foreign exchange.(2007) Lipitor, for the treatment of elevated LDL-cholesterol levels in the blood, is the most widely used treatment for lowering cholesterol and the best-selling pharmaceutical product of any kind in the world, with $12.7 billion in worldwide revenues in 2007, a decrease of 2% compared to 2006 despite the favorable impact of foreign exchange, which increased revenues by $360 million, or 3%. In the U.S., revenues of $7.2 billion in 2007 declined 8% compared to 2006. Internationally, Lipitor revenues in 2007 increased 9% compared to 2006, with 7% due to the favorable impact of foreign exchange.
落ち込みの大半は、simvastatin特許切れに伴うのジェネリック製品群との競争激化による。
On May 30, 2007, we announced the return of Lipitor to Express Scripts Inc.'s preferred list of drugs as of June 1, 2007, following our rebate agreement.
On March 5, 2007, Lipitor was approved by the FDA for five new indications in patients with clinically evident heart disease, thereby expanding the U.S. label from primary prevention in moderate-risk patients to include secondary prevention in high-risk patients. Lipitor is now the only cholesterol-lowering medicine approved for the reduction in risk of hospitalization due to heart failure. These new indications have been incorporated into promotional materials, including a new direct-to-consumer (DTC) advertising campaign, and support the incremental benefit and overall safety of using higher doses of Lipitor.
★Caduet (amlodipine+atorvastatin)高血圧、コレステロール低下【2008】Caduet, a single pill therapy combining Norvasc and Lipitor, recorded worldwide revenues of $589 million, an increase of 4% for 2008, compared to 2007, due primarily to growth in new launch countries, partially offset by lower revenues in the U.S., due to the introduction of generic amlodipine besylate and increased competition in the hypertension market. A more focused message platform and highly targeted consumer campaign have recently stabilized the rate of new patient starts in the U.S.(2007) Caduet, a single pill therapy combining Norvasc and Lipitor, recorded worldwide revenues of $568 million, an increase of 54% for 2007, compared to 2006. This was largely driven by a more focused message platform and a highly targeted consumer campaign in the U.S. Caduet was launched in the U.S. in May 2004 and continues to grow at significantly higher rates than the overall U.S. cardiovascular market. However, with the introduction of generic amlodipine besylate, in addition to increased competition, growth has begun to slow. During 2007, Caduet was launched in France, Australia and Taiwan.
★Norvasc (amlodipine) Ca拮抗剤;米国独占権喪失2007.3【2008】Norvasc, for treating hypertension, lost exclusivity in the U.S. in March 2007. Norvasc also experienced patent expirations in most other major markets, with the exception of Canada. Norvasc worldwide revenues in 2008 decreased 25% compared to 2007.(2007) Norvasc, for treating hypertension, lost exclusivity in the U.S. in March 2007, six months earlier than expected, due to an appellate court decision that was counter to three previous trial court rulings in Pfizer's favor. Norvasc has also experienced patent expirations in many E.U. countries, but maintains exclusivity in certain other major markets, including Japan (where the Norvasc patent will expire in March 2008), and Canada (where the Norvasc patent will expire in August 2010). Norvasc worldwide revenues in 2007 decreased 38% compared to 2006
★Chantix/Champix [varenicline tartrate]禁煙;米国特許失効2018 【2008】the first new prescription treatment to aid smoking cessation in nearly a decade.Chantix/Champix, the first new prescription treatment to aid smoking cessation in nearly a decade, became available to patients in the U.S. in August 2006 and in select E.U. markets in December 2006 and has been launched in all major markets. Chantix/Champix has been prescribed to more than ten million patients globally since its launch. Chantix/Champix recorded worldwide revenues of $846 million in 2008, a decrease of 4% compared to 2007. In the U.S., revenues of $489 million in 2008 declined 30% compared to the same period in 2007 following changes to the Chantix U.S. label during 2008. Internationally, revenues of $357 million in 2008 increased 95% compared to 2007, due primarily to launches in additional countries and continued growth in the U.K., Spain, Canada, Belgium and Japan.In January 2008, we added a warning to Chantix's label in the U.S. that patients who are attempting to quit smoking by taking Chantix should be observed by a physician for neuropsychiatric symptoms like changes in behavior, agitation, depressed mood, suicidal ideation and suicidal behavior. A causal relationship between Chantix and these reported symptoms has not been established.
In May 2008, we updated the Chantix label in the U.S. to provide further guidance about the use of Chantix. The updated label advises that patients should stop taking Chantix and contact their healthcare provider immediately if agitation, depressed mood, or changes in behavior that are not typical for them are observed, or if they develop suicidal thoughts or suicidal behavior.
U.S. prescription trends and U.S. revenues for Chantix have declined following the addition of the warnings to the product's label in the U.S. We are continuing our educational and promotional efforts, which are focused on the Chantix benefit-risk proposition, the significant health consequences of smoking and the importance of the physician-patient dialogue in helping patients quit smoking. In September 2008, the U.S. branded direct-to-consumer campaign was relaunched with print, television and web advertising.■神経系 ★Lyrica (pregabalin)[Pregabalin]てんかん/post-herpetic neuralgia/糖尿病性神経障害;米国特許失効2018 Epilepsy, post-herpetic neuralgia and diabetic peripheral neuropathy【2008】In June 2007, Lyrica was approved and subsequently launched in the U.S. for the management of fibromyalgia, one of the most common chronic pain conditions.Lyrica, indicated for the management of post-herpetic neuralgia (PHN), diabetic peripheral neuropathy (DPN) and fibromyalgia, and as adjunctive therapy for adult patients with partial onset seizures in the U.S., and for neuropathic pain and general anxiety disorder (GAD) outside the U.S., recorded worldwide revenues of $2.6 billion in 2008, an increase of 41% compared to 2007. In June 2007, Lyrica was approved in the U.S. for the management of fibromyalgia, one of the most common chronic, widespread pain conditions, which affects more than five million Americans. Lyrica is the leading branded treatment for fibromyalgia, PHN and DPN in the U.S.
In July 2008, an FDA advisory committee concurred with the FDA's finding of a potential increased signal regarding suicidal thoughts and behavior for the class of 11 epilepsy drugs reviewed, including Lyrica and Neurontin. However, the committee determined that the available data did not warrant black box labeling as had been recommended by the FDA. We are confident in the efficacy and safety profile of Lyrica and Neurontin for their approved indications. We have conducted an extensive review of controlled clinical trials and post-marketing reports for both medicines, which showed no evidence of an increased signal regarding suicidal thoughts and behavior. We are working closely with the FDA to update the labeling for these products and we hope that the labeling change will further facilitate important dialogue between patients and their doctors when considering treatment options.【2006】.Lyrica was approved by the FDA in June 2005 for adjuctive therapy for adults with partialonsent epileptic seizures. This indication builton the earlier FDA approval of Lyrica for the treatment of two of the most common forms of neuropathic pain - painful diabetic peripheral neuropathy, a chronic neurologic condition affecting nearly three million Americans, and post-herpetic neuralgia. Lyrica was launched in the U.S., Canada and Italy in September 2005 and is now approved in 77 countries and is currently available in 59 markets.
In December 2006, we filed a supplemental NDA with the FDA for Lyrica for the treatment of fibromyalgia. Several key medicines received approval for new indications in 2006, including approvals for Lyrica for central neuropathic pain and generalized anxiety disorder in the E.U..
Lyrica achieved $1.2 billion in worldwide revenues in 2006, continuing its performance as one of Pfizer's most successful pharmaceutical launches. In September 2006, Lyrica was approved by the European Commission to treat central nerve pain, which is associated with conditions such as spinal injury, stroke and multiple sclerosis. In addition, in March 2006, it was approved by the European Commission to treat generalized anxiety disorder (GAD) in adults, thereby providing a new treatment option for the approximately 12 million Europeans living with GAD.
Lyrica was approved by the FDA in June 2005 for adjunctive therapy for adults with partial onset epileptic seizures. This indication built on the earlier FDA approval of Lyrica for two of the most common forms of neuropathic pain; painful diabetic peripheral neuropathy, a chronic neurologic condition affecting about three million Americans, and post-herpetic neuralgia. Lyrica was launched in the U.S., Canada and Italy in September 2005 and is now approved in 77 countries and available in 59 markets. As of December 2006, more than four million patients have been prescribed Lyrica since its introduction. Lyrica gained a 9.6% new prescription share of the total U.S. anti-epileptic market in December 2006.
★Geodon/Zeldox [ziprasidone]統合失調症/双極性障害【2008】Geodon/Zeldox, a psychotropic agent, is a dopamine and serotonin receptor antagonist indicated for the treatment of schizophrenia and acute manic or mixed episodes associated with bipolar disorder. It is available in both an oral capsule and rapid-acting intramuscular formulation. In 2008, Geodon worldwide revenues grew 18%, compared to 2007. Geodon is supported by Pfizer's recently launched psychiatric field force and Geodon's efficacy and favorable tolerability and metabolic profiles.
★Neurontin (gabapentin)[gabapentine] 抗てんかん/post-herpetic neuralgia Epilepsy and post-herpetic neuralgia【2007】 Lyrica grew to a 10.9% new prescription share of the total U.S. anti-epileptic market in 2007, fueled by strong efficacy, as well as high physician and patient satisfaction. In June 2007, Lyrica was approved in the U.S. for the management of fibromyalgia, one of the most common chronic, widespread pain conditions. This approval represents a breakthrough for the more than six million Americans who suffer from this debilitating condition who previously had no FDA-approved treatment.【2006】
Approval in Japan for treatment of epilepsy - July 2006(Consumer and Commercial Matters)
A number of lawsuits, including purported class actions, have been filed against us in various federal and state courts alleging claims arising from the promotion and sale of Neurontin. The plaintiffs in the purported class actions seek to represent nationwide and certain statewide classes consisting of persons, including individuals, health insurers, employee benefit plans and other third-party payors, who purchased or reimbursed patients for the purchase of Neurontin that allegedly was used for indications other than those included in the product labeling approved by the FDA. In October 2004, many of the suits pending in federal courts, including individual actions as well as purported class actions, were transferred for consolidated pre-trial proceedings to a Multi-District Litigation ( In re Neurontin Marketing, Sales Practices and Product Liability Litigation MDL-1629 ) in the U.S. District Court for the District of Massachusetts. Purported class actions also have been filed against us in various Canadian provincial courts alleging claims arising from the promotion and sale of Neurontin.
A number of individual lawsuits have been filed against us in various U.S. federal and state courts and in certain other countries alleging personal injury, including suicide and suicide attempt in certain cases, as a result of the purported ingesting of Neurontin. Certain of the federal court actions have been transferred for consolidated pre-trial proceedings to the same Multi-District Litigation referred to in the preceding paragraph.
★Zoloft[sertraline]うつ病/不安障害；;米国市場独占を2006.6に喪失。【2008】★Aricept[donepezil HCl]アルツハイマー;米国特許失効2010【2008】 Aricept, discovered and developed by Eisai Co., Ltd., is the world's leading medicine to treat symptoms of Alzheimer's disease. We co-promote Aricept with Eisai in the U.S. and several other countries and have an exclusive license to sell this medicine in certain other countries.
★Celebrex[celecoxib];米国特許失効2014【2008】Celebrex is for the treatment of arthritis pain and inflammation and acute pain. It also was approved by the FDA in July 2005 and in Europe in February 2007 for the treatment of ankylosing spondylitis, a form of spinal arthritis, and in the U.S. in December 2006, for the treatment of juvenile rheumatoid arthritis.Celebrex, a treatment for the signs and symptoms of osteoarthritis and rheumatoid arthritis and acute pain in adults, experienced a 9% increase in worldwide revenues to $2.5 billion in 2008, supported by continued educational and promotional efforts highlighting Celebrex's efficacy and safety profile.
★【2008】■パイプライン /2007.7.31
●PRISTIQ(desvenlafaxine) うつ病 a serotonin norepinephrine reuptake inhibitor, 米国申請2005.12.22、承認2008.2.29；[適応症]for the treatment of major depressive disorder EU申請2007.9 [a non-hormonal treatment for vasomotor symptoms associated with menopause] の適応は2007.7.23にapprovable letterを受けたが、この適応ではPristiqに伴う強力 かつ重篤な循環器・肝臓系副作用に関する追加データを要求された。 【2008】
PRISTIQ, for the treatment of major depressive disorder, competes directly with our EFFEXOR family of products. We shifted promotional support from EFFEXOR XR (extended release capsules) to PRISTIQ following its approval by the FDA in February 2008 and its subsequent launch in May 2008. This shift in promotional support resulted in a slight decline in demand for EFFEXOR XR (extended release capsules), and sales of EFFEXOR may be adversely impacted over time by the reduction in promotional support.【2007】
In particular, we note that, if approved, PRISTIQ will face competition from our EFFEXOR family of products and other marketed antidepressants.●Effexor 【2008】
Our EFFEXOR family of products, as well as PRISTIQ, competes against another serotonin norepinephrine reuptake inhibitor (SNRI), several selective serotonin reuptake inhibitors (SSRIs) and other antidepressant products. The expiration of the venlafaxine compound patent in the United States in June 2008 and in most major European markets in December 2008 has resulted in the introduction of a number of generic EFFEXOR (immediate release tablets) in the United States and both generic EFFEXOR (immediate release tablets) and generic EFFEXOR XR (extended release capsules) in a number of major global markets. Additionally, the increasing availability of generic versions of the active ingredient in several SSRIs and other antidepressant products puts competitive pressure on EFFEXOR XR (extended release capsules) and PRISTIQ. Late in 2005, we reached agreement with Teva on a settlement of the United States patent litigation pertaining to Teva's proposed generic version of EFFEXOR XR (extended release capsules). Under licenses granted to Teva as part of the settlement, Teva launched a generic version of EFFEXOR (immediate release tablets) in the United States in August 2006 and will be permitted to launch a generic version of EFFEXOR XR (extended release capsules) in the United States beginning on July 1, 2010, subject to earlier launch based on certain specified events. Events that could trigger an earlier United States market entry by Teva with generic versions of EFFEXOR XR (extended release capsules) include specified market conditions and developments regarding the applicable Wyeth patents, including the outcome of other generic challenges to these patents. Seven lawsuits concerning such generic challenges currently are pending. There can be no assurance that the outcome of these litigations or the occurrence of specific market conditions will not trigger generic entry by Teva or another generic manufacturer before July 1, 2010. We estimate that approximately 98% of EFFEXOR (immediate release tablets) prescriptions in the United States have been converted to generic versions following Teva's launch of its generic version in August 2006 and the subsequent launch of other generic versions in mid-2008, and we cannot exclude the possibility that the introduction of generic versions of EFFEXOR (immediate release tablets) in the United States will adversely impact our United States sales of EFFEXOR XR (extended release capsules), though we have not experienced any significant impact to date.In early 2008, we settled our United States patent litigation with Osmotica, which had filed an NDA pursuant to 21 U.S.C. 355(b)(2) seeking FDA approval to market extended release venlafaxine HCl tablets. Venlafaxine HCl is the active ingredient used in EFFEXOR XR (extended release capsules). Under the terms of the settlement, we granted Osmotica a license under certain patents pursuant to which Osmotica will pay us a royalty on sales of its extended release venlafaxine HCl tablet. In May 2008, the FDA approved Osmotica's tablet product but did not rate it as therapeutically equivalent to EFFEXOR XR (extended release capsules). Therefore, Osmotica's tablet product ordinarily will not be substitutable for EFFEXOR XR (extended release capsules) at the pharmacy level. Osmotica launched its extended release tablet in October 2008, which likely will negatively impact our future sales of EFFEXOR XR (extended release capsules).
In 2008, we reached separate agreements with Impax and Anchen on settlements of the United States patent litigations pertaining to each party's proposed generic version of EFFEXOR XR (extended release capsules). Under the terms of each settlement, we granted Impax and Anchen separate licenses that would permit each entity to launch its generic version of EFFEXOR XR (extended release capsules) on or after June 1, 2011, subject to earlier launch in limited circumstances but in no event earlier than January 1, 2011. Based on these settlement agreements, we expect that the launches of these generic alternatives will further erode our sales of EFFEXOR XR (extended release capsules) starting in 2011.
In addition, pursuant to an agreement reached with Teva with respect to a generic version of EFFEXOR XR (extended release capsules) in Canada, Teva launched a generic version of EFFEXOR XR (extended release capsules) in Canada in December 2006. Our combined net revenue in Canada from EFFEXOR (immediate release tablets) and EFFEXOR XR (extended release capsules) has decreased significantly since the availability of generic versions in that market. Additionally, the compound patent for venlafaxine in most other markets outside the United States expired in December 2008, and generic versions of EFFEXOR (immediate release tablets) and EFFEXOR XR (extended release capsules) have been introduced in a number of major non-United States markets. While the impact on our overall EFFEXOR results for 2008 was limited, we expect a significant impact on our sales of EFFEXOR XR (extended release capsules) throughout 2009 as generic versions are introduced in additional markets outside the United States. As generic competition intensifies globally and additional generic SSRIs, SNRIs and other antidepressant products enter markets, additional competitive pressure will occur.
【2007】
Effexor(R)（EffexorおよびEffexor XR）は、世界でトップの売上ならびに処方量を誇る抗うつ薬であり、大うつ病、全般性不安障害、社会不安障害、パニック障害の成人患者に対する重要な治療薬として使用されています。Our EFFEXOR family of products competes against another serotonin norepinephrine reuptake inhibitor (SNRI), several selective serotonin reuptake inhibitors (SSRIs), and other antidepressant products. The increasing availability of generic versions of the active ingredient in several SSRIs and other antidepressant products puts competitive pressure on EFFEXOR (immediate release tablets) and EFFEXOR XR (extended release capsules). Pursuant to the settlement agreement we entered into with Teva with respect to the U.S. patent litigation pertaining to Teva's generic version of EFFEXOR XR (extended release capsules), Teva launched a generic version of EFFEXOR (immediate release tablets) in the United States in August 2006 and will be permitted to launch a generic version of EFFEXOR XR (extended release capsules) in the United States beginning on July 1, 2010, subject to earlier launch based on certain specified events. Events that could trigger an earlier U.S. market entry by Teva with generic versions of EFFEXOR XR (extended release capsules) include specified market conditions and developments regarding the applicable Wyeth patents, including the outcome of other generic challenges to these patents. Six lawsuits concerning such generic challenges currently are pending. There can be no assurance that the outcome of these litigations or the occurrence of specific market conditions will not trigger generic entry by Teva or another generic manufacturer before July 1, 2010. We estimate that approximately 96% of EFFEXOR (immediate release tablets) prescriptions in the United States have been converted to Teva's generic version since the August 2006 launch, and we cannot exclude the possibility that Teva's introduction of a generic version of EFFEXOR (immediate release tablets) in the United States could adversely impact our U.S. sales of EFFEXOR XR (extended release capsules), though we have not experienced any significant impact to date.
In August 2007, we received notice that Sun had filed an ANDA with the FDA for a venlafaxine HCl extended release tablet product. We granted Sun a covenant not to sue with respect to this potential tablet product. The impact of this ANDA on future sales of our EFFEXOR family of products is unclear due to uncertainty regarding if and when the FDA will approve the ANDA (which should not be earlier than June 13, 2008). In early 2008, we reached a proposed settlement of our U.S. patent litigation with Osmotica Pharmaceutical Corp., which has filed an NDA pursuant to 21 U.S.C. 355(b)(2) seeking FDA approval to market an extended release venlafaxine tablet. Under the terms of the proposed settlement, we would grant Osmotica a royalty-bearing license under certain patents. The effectiveness of the proposed settlement, which we have elected to submit to the FTC for review, is subject to the court entering certain orders requested by the parties. In the event that Sun and/or Osmotica obtain FDA approval and successfully launch a venlafaxine extended release tablet, our sales of EFFEXOR XR (extended release capsules) would be negatively impacted.
In addition, pursuant to an agreement reached with Teva with respect to a generic version of EFFEXOR XR (extended release capsules) in Canada, Teva launched a generic version of EFFEXOR XR (extended release capsules) in Canada in December 2006. Teva's launch decreased our net sales significantly in that market, and we believe that the recent entry of additional generic competition into the Canadian market will increase this decline. As a result of this additional generic competition, our royalty from Teva on its Canadian sales of generic extended release venlafaxine HCl capsules has been suspended.
Generic versions of EFFEXOR (immediate release tablets) and EFFEXOR XR (extended release capsules) also have been introduced in select markets outside the United States and Canada. As generic competition intensifies globally and additional generic SSRIs, SNRIs and other antidepressant products enter markets, additional competitive pressure will occur, and we expect lower sales of our EFFEXOR family of products.
【2007特許】
In January 2006, we settled U.S. patent litigation with respect to EFFEXOR XR and granted certain licenses to Teva Pharmaceutical Industries, Ltd. and Teva Pharmaceuticals USA, Inc. (Teva) in connection with the settlement. The patents involved in the Teva litigation, which expire in 2017, relate to methods of using extended release formulations of venlafaxine HCl. These patents are the subject of pending litigation with other generic manufacturers. In 2007, we granted Sun Pharmaceutical Industries Ltd. (Sun) a covenant not to sue under these patents limited to the extended release tablet product defined in an Abbreviated New Drug Application (ANDA) filed by Sun with the U.S. Food and Drug Administration (FDA). In addition, in early 2008, we reached a proposed settlement with Osmotica Pharmaceutical Corp. (Osmotica), which has filed a New Drug Application (NDA) seeking FDA approval to market an extended release venlafaxine tablet product. Under the terms of the proposed settlement, we would grant Osmotica a royalty-bearing license under certain of our patents.●Prevnar 肺炎球菌感染症予防ワクチン 【2009】
Prevnar/Prevenar 13 Infant was approved by the EU member states in December 2009 and in the U.S. in February 2010.【2008】
We have an investigational 13-valent pneumococcal vaccine, the tradename of which is PREVNAR 13, for which we began filing applications for marketing approval in December 2008. A competitor has developed a 10-valent pneumococcal vaccine, which was recently approved for sale in Canada and is pending approval in other markets. In January 2009, the European Medicines Agency's (EMEA) Committee for Medicinal Products for Human Use (CHMP) recommended approval of the 10-valent pneumococcal vaccine for marketing in the EU. If approved for sale in the EU and other markets, the 10-valent pneumococcal vaccine would compete with PREVNAR and/or, if approved, PREVNAR 13.【2007】
Prevnarは、乳幼児向け侵入性肺炎球菌感染症予防ワクチンであり、世界で最も売れているワクチンです。2007年10月、Prevnarはワクチンとしては初めて世界年間売上が20億ドルを達成しました。Prevnarは現在世界86カ国で販売されており、19カ国において国の定期接種プログラムに組み込まれています。さらに今後6カ国がこのワクチンを定期接種プログラムに組み入れる予定を発表しています。We have a 13-valent pneumococcal vaccine under development in Phase 3 clinical trials, and GlaxoSmithKline plc recently filed for regulatory approval in the EU for a ten-valent pneumococcal vaccine, each of which, if approved, would compete with PREVNAR.
●Enbrel (米国、カナダ以外) 【2008】
ENBREL faces competition from multiple alternative therapies depending on the indication and country. ENBREL also faces potential competition from therapies under development. While ENBREL continues to have a market leading position in most markets, including the United States, it has experienced some share loss to competitors.【2007】
エンブレルRは2007年度中も引き続き堅調に売上を伸ばしました。ワイスのマーケティング・パートナーであるアムジェンが発表した米国およびカナダでのエンブレルの売上高は、第4四半期では前年同期から8%増加し8億5,600万ドル、通年では前年から12%増加し32億3,000万ドルとなりました。ワイスは米国、カナダ以外の国でEnbrelの独占販売権を有しています。Enbrelは関節リウマチ、若年性関節リウマチ、強直性脊椎炎、乾癬性関節炎、乾癬などの慢性炎症性疾患の治療薬として承認された画期的な製品です。Enbrelは売上高において世界で5位にランクされている医薬品であり、13カ国で売上高においてトップ10の医薬品にランクされています。また、Enbrelは上位10製品の中で最も急成長を遂げている医薬品です。
2007年11月に米国リウマチ学会で発表されたデータは、Enbrelの優れた臨床効果に加え、Enbrelとメトトレキサートを併用して治療を受けている活動性が高い早期関節リウマチ患者の寛解率はメトトレキサート単独投与群よりも高く、1年で50%が臨床的寛解に達したことを示しています。これらの結果は、臨床的寛解を第一の評価項目とした、関節リウマチ領域における初めての大規模な生物製剤の臨床試験から得られたものです。
ENBREL faces competition from multiple alternative therapies depending on the indication and faces potential competition from therapies under development. In the United States, while ENBREL continues to have a market leading position, it has experienced share loss to competitors.
●Protonix 【2008】
In late 2007, Teva launched a generic version of PROTONIX tablets, despite the existence of the unexpired United States compound patent we exclusively license from Nycomed (previously Altana). Following this “at risk” launch and its resulting impact on the market, we launched our own generic version of PROTONIX tablets in January 2008. However, sales of our own generic have not, and cannot, offset the substantial harm caused by the launch of the infringing generics. A second generic manufacturer, Sun, also launched a generic version of PROTONIX tablets in January 2008, and a 30-month stay against another generic manufacturer, KUDCo, expired on January 25, 2009. See Note 15 to our consolidated financial statements, Contingencies and Commitments, and “Management's Discussion and Analysis of Financial Condition and Results of Operations?Our Challenging Business Environment” in our 2008 Financial Report for a description of the status of our patent litigation with Teva, Sun and KUDCo regarding PROTONIX. Generic competition has negatively impacted, and is expected to continue to negatively impact, our revenue from PROTONIX significantly. PROTONIX also faces competition from other prescription proton pump inhibitors, including several generic products, and multiple over-the-counter remedies.【2007】
Protonix(R)は2007年度も好調な業績を達成しましたが、現在はジェネリック医薬品との競争状態にあります。2008年1月29日、ワイスと事業パートナーであるニコメッド社は、テバ・ファーマスーティカルズUSA社（テバ社）が2007年12月21日にProtonixの後発医薬品であるパントプラゾール錠を米国内で発売したことを受け、Protonix錠の独自の後発品を米国内で発売することを発表しました。さらに、サン・ファーマスーティカル・インダストリーズ社（サン社）も2008年1月30日に米国内で後発品のパントプラゾール錠の米国内発売を発表しています。ワイスは今後もテバ社およびサン社に対しProtonixの特許侵害に対する訴訟を続けていきます。【2007特許】
Certain of the patents covering PROTONIX are the subject of pending litigation.●Zosyn/Tazocin 【2008】
ZOSYN faces generic competition in a number of major markets outside the United States, and may face generic competition in additional countries in the near future. Future sales of ZOSYN will be further negatively impacted in the event of generic competition in the United States and additional major markets. Compound patent protection for ZOSYN expired in the United States in February 2007 and in most major markets outside the United States in July 2007. Certain additional patent protection remains. Our current formulation of ZOSYN was approved by the FDA in 2005 and has additional patent protection until 2023. We believe that the timing and impact of generic competition for ZOSYN in the United States will depend, among other factors, upon the timing and nature of the FDA's response to the citizen petitions filed by Wyeth and third parties regarding ZOSYN, which are discussed in greater detail in Note 15 to our consolidated financial statements, Contingencies and Commitments, in our 2008 Financial Report. However, generic competition for ZOSYN in the United States could occur at any time and likely would have a significant adverse impact on our sales of the product.【2007】
ZOSYN has begun to face generic competition in Spain, Portugal, Greece, France and Switzerland, as well as in several markets outside Europe, and may face generic competition in additional countries in the near future, including in Canada. Future sales of ZOSYN will be further negatively impacted in the event of generic competition in the United States and additional major markets. In February 2007, compound patent protection for ZOSYN expired in the United States. Certain additional process and manufacturing patent protection remains. Our new formulation of ZOSYN was approved by the FDA in 2005 and has additional patent protection extending until 2023. We believe that the timing and impact of generic competition for ZOSYN in the United States will depend, among other factors, upon the timing and nature of the FDA's response to the citizen petitions filed by Wyeth and third parties regarding ZOSYN, which are discussed in greater detail in Note 14 to our consolidated financial statements, Contingencies and Commitments, in our 2007 Financial Report. However, generic competition for ZOSYN in the United States could occur at any time and likely would have a significant adverse impact on our sales of the product.【2007特許】
Compound patent protection for ZOSYN expired in the United States in February 2007. Certain additional process and manufacturing patent protection remains. Our new formulation of ZOSYN was approved by the FDA in 2005 and has additional patent protection extending to 2023. We believe that the timing and impact of generic competition for ZOSYN in the United States will depend, among other factors, upon the timing and nature of the FDA's response to the citizen petitions filed by Wyeth and third parties regarding ZOSYN, which are discussed in greater detail in Note 14 to our consolidated financial statements, Contingencies and Commitments, in our 2007 Financial Report. However, generic competition for ZOSYN in the United States could occur at any time and likely would have a significant adverse impact on our sales of the product.●Premarin 関連製品 【2008】
Our conjugated estrogens products, including PREMARIN and PREMPRO, may be subject to generic competition, as PREMARIN's natural composition is not subject to patent protection, and we depend on trade secrets and other non-patent rights to protect against alternative products being introduced. Certain competitors may be conducting research and development activities in competing estrogen and other products targeted for PREMARIN's approved indications.【2007】
Our conjugated estrogens products, including PREMARIN and PREMPRO, may be subject to generic competition, as PREMARIN's natural composition is not subject to patent protection, and we may depend on trade secret and other non-patent rights to protect against alternative products being introduced. Certain competitors may be conducting research and development activities in competing estrogen and other products targeted for PREMARIN's approved indications.【2007特許】
In addition, we have been involved in various other legal proceedings involving allegations of injuries caused by our pharmaceutical products. These include individual lawsuits and putative class actions in state and federal courts in the United States and foreign jurisdictions involving allegations of injuries caused by PREMPRO or PREMARIN, two of our hormone therapy products. Of the 27 hormone therapy cases alleging breast cancer that have been resolved after being set for trial, 22 have now been resolved in our favor (by voluntary dismissal by the plaintiffs, summary judgment, defense verdict or judgment for us notwithstanding the verdict), several of which are being appealed by the plaintiff. Of the remaining five cases, two such cases have been settled, one resulted in a plaintiffs' verdict that was vacated by the court and a new trial ordered (which plaintiffs have appealed), and two resulted in plaintiffs' verdicts that we plan to appeal. Additional cases have been voluntarily dismissed by plaintiffs before a trial setting. Trials of additional hormone therapy cases also are scheduled throughout 2008. We also face putative class action lawsuits from users of PREMPRO or PREMARIN seeking medical monitoring and purchase price refunds, as well as other damages. While most of these putative class actions have been dismissed or withdrawn, a motion for class certification was recently denied without prejudice in a California statewide refund class action and a hearing in a similar case in West Virginia is set for later this year.●TYGACIL(一般名：チゲサイクリン） 【2008】
TYGACIL, which was approved in June 2005 for treatment of complicated skin and skin structure infections and complicated intra-abdominal infections, faces competition from a number of I.V. antibiotics approved for these indications, as well as several others that are used off-label. Approvals of new products for complicated skin and skin structure infections that may compete with TYGACIL are anticipated in the next few years.【2007】
2007年10月、米国食品医薬品局（FDA）は市中肺炎の治療に対し、この種の抗菌剤としては初めて、TYGACIL(一般名：チゲサイクリン）の適応追加申請書を受理しました。TYGACIL, which was approved in June 2005 for treatment of complicated skin and skin structure infections and complicated intra-abdominal infections, faces competition from a number of I.V. antibiotics approved for these indications, as well as several others that are used off-label. Approvals of new products for complicated skin and skin structure infections that may compete with TYGACIL are anticipated in the next few years.
●TORISEL(一般名：テムシロリムス） 【2008】
TORISEL, which was approved in 2007 for use in the treatment of patients with advanced renal cell carcinoma, faces competition from currently-approved products for this indication, and will face competition from several new compounds pending approval and from certain products in late stage development, if such compounds and products are approved.【2007】
2007年11月、欧州連合は進行性腎細胞癌の第一選択の治療薬としてTORISEL(一般名：テムシロリムス）を承認しました。Toriselは同じ適応に対し2007年5月には米国でも承認されました。TORISEL, which was approved in 2007 for use in the treatment of patients with advanced renal cell carcinoma, faces competition from biologics approved for this indication as well as several oncology products that are used off-label.
●VIVIANT (一般名：バゼドキシフェン) 【2008】 【2007】
2007年12月には、ワイスは閉経後骨粗鬆症予防を目的とした、選択的エストロゲン受容体モジュレーター（Selective Estrogen Receptor Modulator： SERM）であるVIVIANT(TM) (一般名：バゼドキシフェン)の適応に対し米国食品医薬品局（FDA）から2通目の新薬承認通知を受領しました。FDAは現在ワイスに対し、骨粗鬆症の治療ならびに予防のためのViviantの適応について検討するため7月に諮問委員会を開催する予定である旨を通知しています。●アルツハイマー治療薬bapineuzumab (開発番号：AAB-001） 【2008】 【2007】
2007年12月、ワイスとパートナーのエラン社は、中度から軽度のアルツハイマー病の患者を対象とした、アルツハイマー治療薬bapineuzumab (開発番号：AAB-001）の第3相臨床試験を開始したと発表しました。●RELISTOR(TM)（一般名：メチルナルトレキソン） 【2007】
2008年1月10日には、ワイスとパートナーのプロジェニクス・ファーマスーティカルズは、米国食品医薬品局が、緩和ケアを受けている患者さんのオピオイド誘発性便秘（OIC）の治療のための皮下注RELISTOR(TM)（一般名： メチルナルトレキソン）の新薬申請を検討する実行日程を3ヶ月延長したと発表しました。FDAの新しい実行日は2008年4月30日です。● 【2008】 【】 ★追加適応 ■Rx製品一覧 /2007.12.26
Compound_Name Therapeutic_Area Indication 備考 Phase I PF-514273 Cardiovascular, Metabolic & Endo Diseases Obesity Phase I CP-800569 Cardiovascular, Metabolic & Endo Diseases Atherosclerosis Phase I CE-326597 Cardiovascular, Metabolic & Endo Diseases Obesity Phase I PF-3185043 Cardiovascular, Metabolic & Endo Diseases Atherosclerosis Phase I PF-3392455 Cardiovascular, Metabolic & Endo Diseases Hypertension Phase I PF-277343 Dermatology Alopecia Phase I PF-885706 Gastrointestinal / Hepatology Gastroesophageal Reflux Disease Phase I CP-424391 Gastrointestinal / Hepatology Gastroesophageal Reflux Disease Phase I PF-4548043 Gastrointestinal / Hepatology Gastroesophageal Reflux Disease Phase I PF-446687 GenitoUrinary Sexual Health Phase I PF-708093 Infectious Diseases Bacterial Infections Phase I sulopenem prodrug Infectious Diseases Bacterial Infections Phase I PF-4522625 Infectious Diseases Seasonal Flu Phase I sulopenem Infectious Diseases Bacterial Infections Phase I CP-751871 Inflammation Rheumatoid Arthritis
Lung cancerPhase I PF-755616 Inflammation Rheumatoid Arthritis Phase I PD-360324 Inflammation Rheumatoid Arthritis Phase I CP-903397 Neuroscience Schizophrenia Phase I PF-2545920 Neuroscience Schizophrenia Phase I PF-217830 Neuroscience Schizophrenia Phase I PF-572778 Neuroscience Generalized Anxiety Disorder Phase I PF-3084014 Neuroscience Alzheimer's Disease Phase I PF-2400013 Neuroscience Schizophrenia Phase I PF-3463275 Neuroscience Schizophrenia Phase I PF-3654746 Neuroscience Attention Deficit Hyperactivity Disorder Phase I PD-332991 Oncology Cancer Phase I PD-325901 Oncology Cancer Phase I CP-870893 Oncology Cancer Phase I PF-2341066 Oncology Cancer Phase I PF-337210 Oncology Cancer Phase I PF-562271 Oncology Cancer Phase I PF-299804 Oncology Cancer Phase I PF-3814735 Oncology Cancer Phase I PF-477736 Oncology Cancer Phase I PF-738502 Pain Fibromyalgia Phase I PF-3557156 Pain Pain Phase I PF-4136309 Pain Pain Phase I PF-4480682 Pain Neuropathic Pain Phase I Phase II PF-610355 Allergy / Respiratory Asthma Phase II UK-432097 Allergy / Respiratory Chronic Obstructive Pulmonary Disease Phase II CP-866087 Cardiovascular, Metabolic & Endo Diseases Obesity Phase II PF-734200 Cardiovascular, Metabolic & Endo Diseases Diabetes Mellitus-Type II Phase II PD-348292 Cardiovascular, Metabolic & Endo Diseases Thrombosis Phase II CP-533536 Cardiovascular, Metabolic & Endo Diseases Bone Healing Phase II ET-642 Cardiovascular, Metabolic & Endo Diseases Atherosclerosis Phase II ET-216 Cardiovascular, Metabolic & Endo Diseases Atherosclerosis Phase II PF-489791 Cardiovascular, Metabolic & Endo Diseases Hypertension Phase II PH-794428 Cardiovascular, Metabolic & Endo Diseases Short Stature/Growth Problems Phase II PF-275366 Dermatology Prevention of Excessive Sebum Phase II UK-157147 Dermatology Alopecia Phase II PF-547659 Gastrointestinal / Hepatology Ulcerative Colitis Phase II PF-3491390(Idun 6656/IDN6656) Gastrointestinal / Hepatology Liver Fibrosis
(Pan-Caspase Inhibitor)Phase II PfizerはIdun Pharmaceuticalsを2005.2買収。 PD-299685 GenitoUrinary Hot flashes Phase II UK-369003 GenitoUrinary Lower Urinary Tract Symptoms Phase II PF-868554 Infectious Diseases Hepatitis C Virus Phase II UK-453061 Infectious Diseases Human Immunodeficiency Virus Phase II PF-232798 Infectious Diseases Human Immunodeficiency Virus Phase II CP-690550 Inflammation Rheumatoid Arthritis & Transplant Rejection
(Janus kinase 3（JAK3）は、複数のサイトカインによるシグナル伝達に必要であることから、臨床における免疫抑制の優れた標的である。経口投与で有効な特異的JAK3 inhibitor with immunosuppressive properties under development for transplantation.)Phase II CP-195543 Inflammation Rheumatoid Arthritis
(a novel orally active, potent and. selective leukotriene B4 receptor antagonist)Phase II PH-797804 Inflammation Rheumatoid Arthritis
(a p38 inhibitor, safe and tolerated as a monotherapy agent for 12 weeks in subjects with RA; a potent ant-inflammatory drug that may reduce the inflammation that is associated with COPD. )Phase II SC-84250 Inflammation Osteoarthritis Phase II CE-224535 Inflammation / Pain Rheumatoid Arthritis & Pain Phase II PF-4360365 Neuroscience Alzheimer's Disease Phase II 日本P1 PD-332334 Neuroscience Generalized Anxiety Disorder Phase II PD-200390 Neuroscience Insomnia Phase II CP-448187 Neuroscience Depression Phase II PF-4494700 Neuroscience Alzheimer's Disease Phase II CP-751871 Oncology Lung Cancer, Genitourinary, Breast Cancer Phase II PF-3512676
(CpG7909)Oncology Breast Cancer
(toll-like受容体9作動剤)Phase III中止 Coley社オリジン;日本P1;開発中止2007.6 SU-14813 Oncology Breast Cancer Phase II AG-13958 Ophthalmology Age-Related Macular Degeneration Phase II PF-3187207 Ophthalmology Glaucoma Phase II PF-4523655 Ophthalmology Age-Related Macular Degeneration Phase II S,S-reboxetine Pain Pain Phase II CJ-23423 Pain Osteoarthritis Phase II PF-4383119 Pain Pain Phase II PF-592379 Pain Pain Phase II ★apixaban Cardiovascular, Metabolic & Endo Diseases Thrombosis Treatment, Acute Coronary Syndrome Phase II ★Eraxis Vfend combo Infectious Diseases Fungal Infections Phase II ★Maraviroc Inflammation Rheumatoid Arthritis Phase II ★Geodon Neuroscience Adjunct Bipolar Depression Phase II ★Lyrica Neuroscience Restless Leg Syndrome Phase II ★axitinib Oncology Lung, Gastrointestinal, Breast Cancer, Melanoma Phase II ★CP-675206 Oncology Lung, Genitourinary, Gastrointestinal Cancers Phase II ★Sutent Oncology Genitourinary, Gastrointestinal Cancers Phase II Phase III CP-945598 Cardiovascular, Metabolic & Endo Diseases Obesity
(CB-1 Receptor Antagonist)Phase III 開発中止2008.11.6 apixaban Cardiovascular, Metabolic & Endo Diseases Venous Thromboembolism prevention, Atrial Fibrillation
(Factor Xa Inhibitor)Phase III BMSオリジン、共同開発2007.4 Zithromax/Chloroquine Infectious Diseases Malaria
(5-OS Ribosome Inhibitor)Phase III CP-675206
(ticilimumab)Oncology 転移性Melanoma
(CTLA4 Receptor Antagonist)Phase III axitinib(AG-013736) Oncology Thyroid Cancer
(VEGFR Tyrosine Kinase Inhibitor)Phase III P2結果良好;日本P1 ★axitinib Oncology Pancreatic Cancer
(VEGFR Tyrosine Kinase Inhibitor)Phase III ★Sutent Oncology Breast Cancer
(Multiple Tyrosine Kinase Inhibitor)Phase III ★Sutent Oncology Colorectal Cancer, Lung Cancer
(Multiple Tyrosine Kinase Inhibitor)Phase III ★Maraviroc Infectious Diseases Human Immunodeficiency Virus in Treatment Naive Patients
(CCR5 Antagonist)Phase III ★Lyrica Neuroscience Epilepsy Monotherapy, Generalized Anxiety Disorder (U.S.)
(Alpha-2 Delta Ligand)Phase III ★Geodon Neuroscience Bipolar Relapse Prevention
(D2/5HT2 Antagonist)Phase III Registration lasofoxifene(CP-336,156) Cardiovascular, Metabolic & Endo Diseases Osteoporosis Treatment (planned resubmission of NDA Dec. 07)
(Selective Estrogen Receptor Modulator)Registration 日本P2/3 maraviroc
(UK-427857)Infectious Diseases Human Immunodeficiency Virus in Treatment Experienced Patients
(CCR5 Antagonist)Registration dalbavancin Infectious Diseases Skin and Skin Structure Infections
(Cell Wall Synthesis Inhibitor)Registration Recent Approvals Toviaz (fesosterodine) GenitoUrinary Overactive Bladder (E.U.)
(Muscarinic Receptor Antagonist)承認 Lyrica Pain Fibromyalgia (US)/Generalized Anxiety Disorder (EU)
(Alpha-2 Delta Ligand)承認 Projects Discontinued from Development PF-431499 Cardiovascular, Metabolic & Endo Diseases Obesity P1中止 PF-807925 Cardiovascular, Metabolic & Endo Diseases Atherosclerosis P1中止 PF-3491165 Cardiovascular, Metabolic & Endo Diseases Atherosclerosis P1中止 PF-3052334 Cardiovascular, Metabolic & Endo Diseases Atherosclerosis P1中止 PF-915275 Cardiovascular, Metabolic & Endo Diseases Diabetes Mellitus-Type II P1中止 CP-868596 Oncology Cancer P1中止 CE-245677 Oncology Cancer P1中止 AG-24322 Oncology Cancer P1中止 CP-778875 Cardiovascular, Metabolic & Endo Diseases Atherosclerosis P2中止 CP-741952 Cardiovascular, Metabolic & Endo Diseases Obesity P2中止 CP-640922 Dermatology Skin Improvement P2中止 PD-325901 Oncology Lung Cancer P2中止 PF-3512676 Oncology Lung cancer
(Toll-like receptor 9 (TLR9) agonist)P3中止 追加メモ Capravirine(AG1549/S1153) HIV
(non-nucleoside reverse transcriptase inhibitors (NNRTIs))P2b中止 Pfizer開発中止2005.7;塩野義オリジン Certolizumab pegol(Cimzia;CDP-870) Rheumatoid Arthritis
(TNF-receptor p55 PEG)P3中止 ;Celltechオリジン CP-644,673 (P57)
(A HMG-COA REDUCTASE INHIBITOR)中止 ;lic. from Phytopharm Edotecarin(PHA-782615;旧J-107088 ;旧ED-749) 脳腫瘍(Glioblastoma Multiforme)
(an indolocarbazole topoisomerase I inhibitor which is structurally distinct from the camptothecins. ;a derivative of NB-506)P3中止 2005.7開発中止;万有製薬オリジン Sumanirole(PNU-95666 E) パーキンソン病とレストレスレッグス症候群
(a highly dopamine D2-selective receptor agonist)P3中止 開発中止2004.7 Torcetrapib(CP-529414) 高脂血症
(CETP(Cholesteryl Ester Transfer Protein)阻害剤；善玉コレステロールHDLを上昇させる新薬)P3中止 開発中止2006.12
●Pfizer ■Investors ●SEC Filings 10-K Annual report[2010.2.26; pdf,157p] - [doc] - [xls] 10-K Annual report[2009.2.27; pdf,157p] - [xls] - [doc] 10-K Annual report[2008.2.29; pdf,141p] - [xls] - [doc] 10-K Annual report[2007.3.1; pdf,188p] -[xls] -[doc] ●Financial Report 2009 Annual Review - 2009 Financial Report - Download and Print Presentation 2008 Annual Review - 2008 Financial Report - Download and Print Presentation (2.79 MB) PDF Annual Review 2007[pdf] Financial Report 2007[pdf] Annual Review 2006 - [pdf] Financial Report 2006 - [pdf] ●News Release Pfizer Reports Fourth-Quarter and Full-Year 2009 Results; [2010.2.3] Pfizer Reports Fourth-Quarter and Full-Year 2008 Results and 2009 Financial Guidance[2009.1.26] Pfizer Reports Fourth-Quarter and Full-Year 2007 Results and 2008 Financial Guidance[2008.1.23] Pfizer Achieves Key 2006 Financial Targets[2007.1.23] ●Products～全製品の添付文書 ●Research & Development～The Pfizer Pipeline ●Previous Pharmacia Web Sites
●ファイザー株式会社 - 2003.8.1 ファルマシア社と経営統合、ファィザー製薬→ファイザー（株）に ●プレスリリース ファイザー株式会社 2008年度業績発表～売上高は前年比0.7％増の4,395億円に～[2009.3.3] ファイザー社2008年度第4四半期および2008年度通期の決算報告、ならびに2009年度の財務指標[2009.2.2] ファイザー株式会社 2007年度の業績を発表[2008.2.28] ファイザー社2007年度第4四半期および2007年度通期の決算報告、ならびに2008年度の財務指標[2008.2.4] ファイザー株式会社 2006年度の業績を発表[2007.2.28] ファイザー社2006年度決算報告[2007.1.31] ファイザー、2005年度売上高は前年比5.9％増の4,083億円に[2006.3.1] ファイザー、2004年度売上高は前年比25.2％増の3,856億円に[2005.2.28] ファイザー株式会社、2003年度売上高は前年比23.8％増の3,081億円に[2004.3.4] ファイザー社、2003年度決算報告[2004.3.4] ファイザー製薬、2001年度売上高は前年比29％増の2,199億円に[2002.3.7] ファイザー社、２００２年第４四半期と２００２年通期の力強い決算を発表、２００３年
も好調な業績を見込む[2003.1.31] ★旧ファルマシア社プレスリリース ●医療従事者[安全性情報]No.225[2006.6.22] 重要な副作用等に関する情報 1 アジスロマイシン水和物 直近３年間（平成15年４月～平成18年３月）の副作用報告（因果関係が否定できないもの）の件数 ・ 肝炎：５例（うち死亡０例） ・ 白血球減少，顆粒球減少，血小板減少：４例（うち死亡０例） ・ 横紋筋融解症：５例（うち死亡０例） 関係企業が推計したおおよその年間使用者数：3000万人（平成17年度） 推定出荷額：約１７５億円(2005) ●「業績好調、ＭＲ増強も」ブーツ社長が記者会見で方針を説明 ファイザー [薬事日報2004.3.8] ファイザー（日本法人）のアラン・Ｂ・ブーツ社長は４日、都内で記者会見し、２００３年度（０２年１２月１日～０３年１１月３０日）の売上高が前年比２３・８％増の３０８１億円となったと説明した。同社は、０４年から０５年にかけて新たに７品目（うち１品目は他社製品のコ・プロモーション）を市場投入する方針で、０４年度に４１３３億円の売り上げを目指す。扱う製品の増加に伴いＭＲ数も２００人増員し、０４年中に３４００人体制とする。
(百万円) 2007 2006 2005 2004 2003 2002 2001 2000 備考 売上高 415,010[100%] 408,291(+5.9)[100%] 385,624 308,116 248,893 219,946 170,100 医療用医薬品事業 393,365(+2.8)[95%] 382,780(+5.5)[93.80%] 農産事業 5,732(+17.0)[1%] 4,901(-5.1)[1.20%] コンシューマーヘルスケア事業 8,913(-25.5)[2%] 11,958(+7.0)[2.90%] 輸出その他 7,000(-19.1)[2%] 8,652(+33.4)[2.10%] 循環器官用薬 [58%] 感染症治療薬 [16%] 感覚器官用薬 [7%] キサラタン緑内障 ホルモン剤 [6%] ジェノトロピン[HGH] 中枢神経系用薬 [6%] 腫瘍用薬 [4%] その他 [3%]
同社の０３年度業績について説明したブーツ社長は伸長の背景として、高脂血症治療薬「リピトール」や高血圧治療薬「ノルバスク」などの主力製品で売り上げが着実に伸長したことに加え、ファルマシアとの統合により、医療用医薬品のみならず、全ての事業部門で売り上げが前年を上回ったことなどを挙げた。うち医療用医薬品は前年比２４・１％増の２８９４億円、一般用医薬品は８７・９％増の７３億円だった。同社では、今年度から０５年度にかけて７品目の新規の開発品目の上市を予定しているほか、３品目の適応拡大を行う方針だ。新たに上市が期待されているのは、「Ｖフェンド」（深在性真菌症）、「デトロール」（過活動膀胱）、「ゾロフト」（うつ病、パニック障害）、「インスプラ」（高血圧症）、「セレコックス」（慢性関節リウマチ、変形性関節症、腰痛症等）、「プロジフ」（深在性真菌症、１月に発売済み）の６品目のほか、「スピーリーバ」（ＣＯＰＤ）を日本ベーリンガー・インゲルハイムとコ・プロモーションを行う予定。
それ以外にも「ジスロマック」（性感染症）、「ザイボックス」（ＭＲＳＡ）、「ジェノトロピン」（成人の成長ホルモン分泌不全症、子宮内発育遅延性低身長症）の適応拡大を見込んでいる。
●「３年後、医療用３８００億円に」ブーツ社長が会見 ファイザー製薬[薬事日報2002.3.11] ★ファイザー製薬の主要製品2001の売上高と疾患別売り上げランキングは、 持続性カルシウム拮抗剤ノルバスク 950億円（前年比13%増、高血圧症1位）、 脂質低下剤リピトール 400億円（216%増、高脂血症3位）、 α1遮断薬カルデナリン 260億円（3%増、高血圧症8位）、 アリセプト 150億円（100%増、アルツハイマー病1位） ★日本での開発状況 抗高脂血症薬ゲムフィブロジル、片頭痛治療薬エレトリプタン、降圧薬ドキサゾシン徐放 錠、うつ病・パニック障害治療薬セルトラリンの四品目が申請中。 抗真菌薬フルコナゾール・プロドラッグは申請準備中。 抗てんかん薬ガバペンチン、抗真菌薬ボリコナゾールの二剤がフェーズⅢ 切迫性尿失禁治療薬ダリフェナシンがフェーズⅡ。
■Pharmacia
2003.4.16 Pfizer社に経営統合。 ●Pharmacia Corporation Annual Report 2001 [Financial Review,40p] 2p目に製品別売上Pharmacia Corporation Annual Report 2000 [Financial Review,33p] --- [Net Sales ,35p]Pharmaceutical Sales Pharmacia Corporation Reports 11% Increase In Earnings Per Share (Eps) For Fourth Quarter Of 2002[2003.2.19]
($ milllion) 2002 2001 2000 1999 1998 備考 ★リウマチ Celebrex 3,050(-2) 3,114(+19%) 2,614(+78%) 1,471(-) - celecoxib Bextra 470 - - - - valdecoxib Daypro ? ??? 145(34) 222(26) 301 oxaprozin(NSAID) Healon ? ??? 127(7) 136(3) 140 hyaluronate ★神経系 Ambien Sanofiへ 902(+28) 705(+35) 523(+17) 449 zolpidem 不眠症 Xanax 314(-3) 323(-1) 327(+2) 320(-) 321 alprazolam 抗不安 Mirapex 207(+40) 148(+30) 113(+39) 81(+65) 49 pramipexoleうつ病 ★眼科 Xalatan 928(+14) 818(+18) 693(+37) 507(+53) 332 latanoprost ★泌尿器 Detrol LA/Detrol 757(+23) 617(+43) 432(+31) 329(+163) 125 tolterodine ★癌 Camptosar 574(-6) 613(+39) 441(+50) 293(+51) 194 irinotecan大腸癌 Pharmorubicin/Ellence 333(+28) 261(+31) 199(-3) 206(+16) 177 epirubicin乳癌 ★ホルモン Genotropin 551(+8) 511(+9) 467(+1) 461(+17) 395 somatropin 成長ホルモン Medrol 329(+2) 323(+14) 284(-5) 297(+13) 264 methylprednisolone Depo-Provera 339(+20) 283(+4) 272(+8) 252(+11) 227 medroxyprogesterone acetate 注射用避妊薬 ★感染症 Cleocin/Dalacin 273(-13) 316(-7) 340(-1) 343(+9) 314 clindamycin Zyvox 199(+85) 108(+125) 48(N/A) --- --- linezolid ★ Nicorette Line ? 299(+37) 218(-7) 234(+10) 213 nicotin ★消化器 Arthrotec 241(+3) 235(-6) 251(-26) 340(-1) 342 misoprostol/diclofenacNa ★血栓 Fragmin 270(+20) 226(+7) 211(-1) 213(+18) 181 dalteparin sodium ★循環器 Aldactone/spiroline 190(+4) 183(-2) 187(-17) 224(+12) 199 spironolactone Pletal 136(+28) 106(+99) 53(+197) 18 --- Cilostazol Covera/Calan 134(-17) 161 153(5) 161(-) 160 verapamil ★婦人科 Cabaser/Dostinex 230(+39) 165(+33) 124(+49) 83(+57) 53 cabergoline ★毛髪用剤 Rogaine/Regaine ? 117(-13) 134(-4) 139(+4) 133 minoxidil Total ? 9,668(+19%) 8,113(+28) 6,334 TOTAL ? ? 8,437(+23) 6,835(50) 4,569
●ファルマシア社、第4四半期の1株当り利益が33％増[01.2.13]
＜主要製品の動向＞
関節炎治療薬「セレブレックス」
世界最大の売上を誇る関節炎治療薬「セレブレックス」の売上は第4四半期7億7,200万ドル、通年では26億ドルに達しました。米国での第4四半期売上は5億9,700万ドルでしたが、これには12月の値上げを控えた卸売り業者による見込み買いも若干寄与しています。ファルマシア社はヨーロッパ主要市場でも「セレブレックス」を次々に導入しており、当第4四半期にはフランスで発売しました。
緑内障治療薬「キサラタン」
緑内障治療薬として世界最大の売上を誇る「キサラタン」は、すべての主要市場で引き続き成長し、第4四半期の売上は前年同期比23％増の1億9,600万ドルに達しました。また、通年の売上は前年度比37％増の6億9,300万ドルでした。「キサラタン」は米国と欧州ですでにマーケットリーダーとしての地位を固めていますが、日本でも発売後わずか21ヵ月で最大の緑内障治療薬となりました。「キサラタン」の売上は、今やその50％以上を米国外が占めています。
抗がん剤「カンプトサール」
「カンプトサール」の第4四半期売上は前年同期比40％増の1億1,600万ドルでした。通年では前年度比50％増の4億4,100万ドルでした。これは「カンプトサール」が4月にＦＤＡ(米国食品医薬品局)により転移性結腸直腸がんの第一次選択薬として承認されたことから、以前よりも早期に使用されるようになったことが寄与しています。「カンプトサール」を使用する治療法は、その生存率の高さから、転移性結腸直腸がん患者の標準的な治療法となっています。
過活動膀胱治療薬「デトロール」
過活動膀胱の主要な治療薬「デトロール」の第4四半期売上は1億1,300万ドル(前年同期比21％増)、通年では4億3,200万ドル（前年度比31％増）を記録しました。また、通年の米国外売上が初めて1億ドルを突破しましたが、これは過活動膀胱治療薬市場の拡大を反映するものです。
ヒト成長ホルモン製剤「ジェノトロピン」
ヒト成長ホルモン製剤として世界をリードしている「ジェノトロピン」の第4四半期売上は1億1,300万ドルで前年同期比9％減となりました。これは世界売上のほぼ半分を占めるヨーロッパ市場で、為替の悪影響が出たことが主因です。通年でも、世界売上は前年度比微増の4億6,700万ドルにとどまりました。一方、米国の新規処方市場では確実にシェアを拡大し、売上は27％増加しました。
抗菌剤「ザイボックス」
重篤なグラム陽性菌感染症の治療薬として2000年4月に米国で発売された「ザイボックス」の第4四半期売上は1,800万ドル、通年では4,800万ドルでした。「ザイボックス」は35年ぶりの全く新しいクラスの抗菌剤であり、英国で今月発売される予定です。
不眠症治療薬「アンビエン」
不眠症治療薬として米国トップの「アンビエン」の第4四半期売上は前年同期比13％増の2億700万ドルでした。通年の売上は前年度比35％増の7億500万ドルでした。米国の不眠症治療薬市場における「アンビエン」のシェアは、すでに55％を超えています。
その他の事項
昨年12月末、FDAはファルマシア社の１日１回投与型の過活動膀胱治療薬「デトロールLA」を承認しました。「デトロールLA」は長時間作用する新剤型を特徴としており、スイスでも承認を受けて「デトルシトールSR」として近く発売される予定です。ファルマシア社は現在、１日２回投与型の「デトロール／デトルシトール」を30カ国以上で販売しています。
また、ファルマシア社は開放隅角緑内障の新治療薬「キサルコム」についても、年末に初の承認をスウェーデンで獲得しました。「キサルコム」はファルマシア社の「キサラタン」とチモロール（広く使用されているベータ遮断薬）の固定配合剤で、強い眼圧降下作用を必要とする患者向けとなっています。ヨーロッパ連合（EU）では「キサルコム」を「相互承認方式」(Mutual Recognition Process) の対象に指定しており、今回のスウェーデンでの承認は、その初適用となったものです。
第4四半期中も、ファルマシア社は引き続き重要な新薬を規制当局に承認申請しました。10月には、パレコキシブの新薬承認申請（NDA）をFDAに提出したと発表しました。パレコキシブは疼痛の治療薬で、注射用COX-2特異的阻害剤としては、初の治験薬です。
主要製品の売上 (単位百万ドル)
2000年度
第4四半期1999年度
第4四半期増減
2000年度
1999年度
増減
米国
世界
米国
世界
米国
世界
米国
世界
米国
世界
米国
世界
セレブレックス
$ 597
$ 772
$ 442
$ 497
35%
55%
$ 2,202
$ 2,614
$ 1,351
$ 1,471
63%
78%
アンビエン
$ 206
$ 207
$ 183
$ 184
13%
13%
$ 700
$ 705
$ 519
$ 523
35%
35%
キサラタン
$ 98
$ 196
$ 82
$ 159
19%
23%
$ 343
$ 693
$ 279
$ 507
23%
37%
ジェノトロピン
$ 20
$ 122
$ 17
$ 135
11%
(9)%
$ 69
$ 467
$ 54
$ 461
27%
1%
カンプトサール
$ 105
$ 116
$ 77
$ 83
37%
40%
$ 404
$ 441
$ 272
$ 293
49%
50%
デトロール/デトルシトール
$ 84
$ 113
$ 70
$ 93
20%
21%
$ 324
$ 432
$ 256
$ 329
27%
31%
クレオシン／ダラシン
$ 41
$ 86
$ 38
$ 90
7%
(4)%
$ 155
$ 340
$ 145
$ 343
7%
(1)%
ザナックス
$ 26
$ 80
$ 16
$ 72
63%
11%
$ 109
$ 327
$ 101
$ 320
8%
2%
メドロール
$ 26
$ 76
$ 21
$ 77
25%
(2)%
$ 88
$ 284
$ 89
$ 297
(1)%
(5)%
デポープロベラ
$ 67
$ 84
$ 47
$ 64
43%
30%
$ 206
$ 272
$ 188
$ 252
10%
8%
アースロテック
$ 19
$ 44
$ 33
$ 75
(42)%
(40)%
$ 131
$ 251
$ 189
$ 340
(30)%
(26)%
ニコレット製品
$ 25
$ 59
$ 24
$ 61
3%
(4)%
$ 88
$ 218
$ 103
$ 234
(15)%
(7)%
フラグミン
$ 12
$ 53
$ 8
$ 60
51%
(11)%
$ 37
$ 211
$ 24
$ 213
54%
(1)%
ファルモルビシン/エレンス
$ 4
$ 47
$ 7
$ 60
(50)%
(22)%
$ 9
$ 199
$ 7
$ 206
15%
(3)%
アルダクトン/スピロ製品
$ 2
$ 42
$ 9
$ 62
(80)%
(32)%
$ 25
$ 187
$ 45
$ 224
(45)%
(17)%
コベラ/カラン/ベラパミル
$ 14
$ 18
$ 30
$ 35
(55)%
(47)%
$ 136
$ 153
$ 143
$ 161
(5)%
(5)%
デイプロ
$ 28
$ 29
$ 39
$ 40
(29)%
(27)%
$ 143
$ 145
$ 218
$ 222
(34)%
(34)%
ロゲイン
$ 27
$ 34
$ 28
$ 38
(7)%
(11)%
$ 103
$ 134
$ 107
$ 139
(4)%
(4)%
ヒーロン
$ 8
$ 34
$ 9
$ 38
(4)%
(11)%
$ 30
$ 127
$ 33
$ 136
(9)%
(7)%
カバサール/ドスチネックス
$ 14
$ 39
$ 8
$ 24
84%
65%
$ 40
$ 124
$ 31
$ 83
29%
49%
ミラペックス
$ 28
$ 36
$ 23
$ 26
25%
33%
$ 88
$ 113
$ 72
$ 81
23%
39%
● ●Products[A-Z]|Products[by category]|Prescription Products ●Investor Relations --- Financial Report～Annual Reports等; Annual report 2001[pdf,78p] --- Financial News --- Pipeline Products ●Newsroom Pharmacia Corporation Reports 11% Increase In Earnings Per Share (Eps) For Fourth Quarter Of 2002[2003.2.19]
●ファルマシア・ジャパン - 2003.8.1 ファィザー（株）に統合 --- 医薬品情報[製品] --- ニュース - ファルマシア社、第4四半期の1株当り利益が33％増[01.2.13] ★2002年2月6日 ファルマシア社、2001年度の1株当り利益が29％増（PDF形式）[10p] 主要品売上 2001 +-[百万ドル] セレブレックス $3,114 19% アンビエン $902 28% キサラタン $818 18% デトロール $617 43% カンプトサール $613 39% ジェノトロピン $511 9% [その他の事項]
ファルマシア社は本日、FDA が高血圧症治療薬であるエプレレノン（選択的アルドステロン・ブロッカー）の新薬承認申請を受理したと発表しました。また、ファルマシア社はエプレレノンを心臓障害に適用するための治験（フェーズⅢ）も完了しつつあり、2003 年度上半期には新薬承認申請を提出できるものと予想しています。
ファルマシア社は、同時に「ベクストラ」(一般名：バルデコキシブ)の詳細な発売スケジュールを明らかにしました。「ベクストラ」は、変形性関節症、成人の慢性関節リウマチ、および生理痛を適応症とする第2 世代のCOX-2 阻害剤です。薬局や卸売業者への販売は1 月から始めていますが、本格的な発売は2002 年4 月の予定です。
初の注射用COX-2 阻害剤である「ダイナスタット」(一般名：パレコキシブ)を2002 年度上半期にヨーロッパ諸国で発売する予定です。
「ベクストラ」と「ダイナスタット」が承認されたことで、ファルマシア社のCOX-2 阻害剤製品は、業界で最も充実したラインアップとなりました。●Pharmacia社の歴史 [Searle] Monsanto社事業部門だったが、Monsanto /Pharmacia-Upjohn合併によるPharmacia Corp[2000.4.3]の一部門になった。 企業としては存続。 ★山木社長が就任会見「開発中の新薬３品目に期待」 ファルマシア[薬事日報2002.6.21] 山木社長は「エプレレノン（アルドステロン受容体拮抗型降圧剤）、デトロール（過活動 膀胱治療剤）、セレコキシブ（ＣＯＸ‐２阻害剤）の三製品が承認され、既存品が売り上 げを維持しつつ新薬がシェアを拡大すれば、2005年には国内売上高ランキングで、トップ １０入りも夢ではない（現在二〇位）。トップ１０入りのためには薬価ベースで2000億円 強の売り上げが必要」と抱負を語った。 申請中の開発品には、エプレレノン（五月九日申請）やデトロール（二月二十八日申請） など10品目がある。申請準備中に末端肥大症治療薬ペグビソマント、フェーズⅢにはセレ コキシブ、ＭＲＳＡ感染症治療剤ザイボックス、緑内障治療薬ザルコム、成人成長ホルモ ン欠損症治療薬ジェノトロピン（効能追加）などがある。 エプレレノンはアルドステロンを抑え込む世界初の薬剤として、日米欧三極で開発され ている（米国は昨年末に申請済み、欧州はフェーズⅢ実施中）。グローバル開発部門長の 田原一二氏は「他社でアルドステロン拮抗剤を開発しているという話は聞いたことがな い」と話す。今後も全世界で数千例を対象にした臨床試験を継続する計画であり、強力な 臓器保護作用を持つ降圧剤として大型化が期待されている。 デトロールは昨年全世界で六億ドルを売り上げている。エプレレノンとデトロールは、 国内ではともに、来年から再来年早々にかけての上市を期待する。山之内製薬と共同開発 中のセレコキシブは、昨年には全世界で三一億ドルを売り上げた大型製品である。 日本法人ファルマシアの2001年医薬品売上高は1069億円（前年比7.6%増、薬価ベース）。 国内製品売上高、 2002 2001 (億円) キサラタン 211(+18) 179(+36) 緑内障治療薬（国内市場ランキング一位）、 ジェノトロピン 204(-2%) 208(-) ヒト成長ホルモン製剤（一位）、 カバサール 88(+42) 62(+107) パーキンソン病薬 ハルシオン 67(-10) 74(-2%) 睡眠導入剤（三位）、 ファルモルビシン 64(+12) ? 抗癌剤 ソル・メドロール ? 64(-) 副腎皮質ホルモン製剤（一位） アルダクトン ? 62(+5) 利尿・降圧剤（二位） from ファイザー製薬とファルマシアが８月統合、新社名は「ファイザー」
ファイザー製薬、ファルマシア [薬事日報 2003.3.10]
■Wyeth
http://www.wyeth.com/; 年間売上高=$15.8 billion(2003) 従業員数 [Wyeth Pharmaceuticals] 17カ国37工場、60カ国で販売。 従業員数44,000 [Prescription Products] [Biopharmaceuticals] [Wyeth Vaccines] [Wyeth Nutritionals] [Wyeth Research] 1993 Women's Health Research Institute設立 [Wyeth Consumer Healthcare] 年間売上高$2.4 billion(2003)。 世界第三位 1998 Solgar Vitamin and Herb Company(栄養剤・ハーブ)を買収 [Fort Dodge Animal Health] 1912設立。 1945年にWyethの事業部になる。従業員数3500 動物用ワクチン世界第１位。 1982 Sherwood Medical(医療機器)を買収 1985 Ives LaboratoriesをWyethに合併 1987 WyethとAyerstを合併→Wyeth-Ayerst Laboratories Bristol-Myersの動物薬部門を買収し、Fort Dodgeに統合。 1988 Parke-Davisの動物薬部門を買収し、Fort Dodgeに統合。Fort Dodgeは米国第三位に 1989 A.H. Robins(OTCメーカー) を買収 1992 AHPはGenetics Instituteの60%取得。 1994 American Cyanamidを買収。その子会社Lederleを含む。 1996 Solvayの世界的動物薬事業を買収→Fort Dodgeに統合。 1996.12 AHPはGenetics Instituteの残りの全株取得、100%子会社化。 1998.3 Wyeth-Ayerst ResearchとGenetics Instituteの研究開発部門統合。 1998 Whitehall-Robins HealthcareがSolgar Vitamin and Herb Companyを買収 2002.3.11 American Home Products[US]は、Wyeth(ワイス)に社名変更。 see History 尚、2001.12 同社が大株主のImmunexがAmgenにより買収。 2008 THERMACAREを買収 2009.1.26 Pfizer社との合併契約 ●会社決算●国別売上高
($000) 2008 2007 2006 2005 2004 2003 2002 2001 2000 売上高 22,833,908 22,399,798 20,350,655 18,755,790 17,358,028 15,850,632 14,584,035 13,983,745 13,081,334 純利益 4,417,833 4,615,960 4,196,706 3,656,298 1,233,997 2,051,192 4,447,205 2,285,294 -901,040 従業員数・期末 47,426 50,527 50,060 49,732 51,401 52,385 52,762 52,289 48,036 研究開発費 3,109,060 2,749,390 2,460,610 2,093,533 ●事業別売上高
($ million) 2008 2007 2006 2005 2004 2003 2002 2001 2000 売上高 22,833.9 22,399.8 20,350.7 18,755.8 17,358.0 15,850.6 14,584.0 13,983.7 13,081.3 米国 10,714.6 11,637.7 11,054.4 9,856.5 9,581.0 9,233.8 英国 1,114.6 1,083.2 999.5 1,088.7 863.0 750.6 その他 11,004.7 9,678.9 8,296.8 6,412.8 5,406.6 4,599.6 ●主要製品売り上げ[Wyeth]
($ MILLION) 2008 2007 2006 2005 2004 2003 2002 2001 2000 売上高 22,833.9(+2) 22,399.8(+10) 20,350.7(+9) 18,755.8(+8) 17,358.0(+10) 15,850.6(+9) 14,584.0 13,983.7 13,081.3 医薬品 19,025.4(+2) 18,622.0(+10) 16,884.2(+10) 15,321.1(+10) 13,964.1(+11) 12,622.7(+8) 11,733.3 ConsumerHealth 2,720.6(-1) 2,736.1(+8) 2,530.2(-1) 2,553.9(-) 2,557.4(+5) 2,434.5(+11) 2,197.4 動物用保健品 1,087.9(+4) 1,041.7(+11) 936.3(+6) 880.8(+5) 836.5(+5) 793.4(+21) 653.3 註）各国内・国外別データあり。Premarinグループは、別紙に製品別データ from 4Q 2004 Net Revenue Report -Product Net Sales Reports;個別製品売上高 ※Enbrel - 当初、北米はImmunex,Wyeth共販、他の全世界はWyethだったが、2001.12の AmgenによるImmnex買収により、北米Amgen,他の全世界Wyethとなった。 ※Alliance収入－Enbrel(北米)分の収入、Altace(ramipril;販売King)およびCypherステント(主成分sirolimus; J&J販売) ●特許期限 /2009.2.27 Product Year ------------------- BENEFIX 2011 rhBMP-2 2014 EFFEXOR/EFFEXOR XR* 2008 ENBREL 2012 PREMPRO 2015 PRISTIQ 2022 PROTONIX** 2011 RAPAMUNE 2014 REFACTO 2010 TORISEL 2014 (if restoration granted, 2019) TYGACIL 2016 XYNTHA 2010 ZOSYN*** 2007 ●Wyeth's Pipeline for Growth [年報2002, 22-23p] ★Women's Health Care Bazedoxifene (TSE-424) Postmenopausal osteoporosis※P3(前年と同) Bazedoxifene/PremarinR Postmenopausal osteoporosis※P3(前年と同) Vasomotor symptoms of menopause※P3(前年と同) Levonorgestrel/EE Continuous Contraception※P3(前年なし) PremarinR low dose Postmenopausal osteoporosis※Regulatory review(前年と同) Vasomotor symptoms of menopause※Regulatory review(前年と同) PremarinR/MPA low dose Postmenopausal osteoporosis※Regulatory review(前年と同) Vasomotor symptoms of menopause※Regulatory review(前年と同) PremarinR/trimegestone Postmenopausal osteoporosis※P3(前年と同) Vasomotor symptoms of menopause※P3(前年と同) Trimegestone/17 s-estradiol Postmenopausal osteoporosis (EU)※P3(前年と同) Vasomotor symptoms of menopause (EU)※Regulatory review(前年と同) ★Neuroscience Therapy EffexorR XR Generalized anxiety disorder in pediatrics※Regulatory review(前年P3) Depression in pediatrics※削除(前年P3) Panic disorder※P3(前年同) Social anxiety disorder (U.S. and Canada)※Regulatory review(前年同) CI-779 Multiple sclerosis※P2(前年なし) ★Vaccines and Infectious Diseases Tigecycline antibiotic (GAR-936) Serious infections※P3(前年なし)※広範囲な抗菌力、耐性菌に有効 Cold-adapted influenza vaccine Liquid formulation※P3(前年同) FluMist intranasal influenza vaccine Frozen formulation※Regulatory review(前年同) PrevnarR Otitis media※削除(前年Regulatory review) ZosynR Nosocomial pneumonia q6h (U.S.)※Regulatory review(前年P3) 9-valent pneumococcal and meningococcal Group C conjugate vaccine※P3(前年同) ★Musculoskeletal Therapies EnbrelR Ankylosing spondylitis(US)※Regulatory review(前年P3) Ankylosing spondylitis(EU)※P3(前年同) Psoriatic arthritis (EU)※Regulatory review Psoriasis※P3(前年P2) Idiopathic pulmonary fibrosis※P2(前年なし) J695 (anti-IL-12) Rheumatoid arthritis (joint with Abbott Laboratories)※削除(前年P2) rhBMP-2 Dental/craniofacial※削除(前年P3) Lumbar interbody spinal fusion (collaboration with Medtronic Sofamor Danek)※削除(前年Regulatory review) Lumbar posterolateral spinal fusion (collaboration with Medtronic Sofamor Danek)※P3(前年同) Orthopedic trauma (long-bone fractures requiring surgery)※Regulatory review(前年同) ★Internal Medicine CordaroneR AQ (amiodarone aqueous) Recurrent ventricular fibrillation and unstable ventricular tachycardia (U.S.)※削除(前年P3) Ertiprotafib (PTP-112) Type II diabetes※削除(前年P2) ProtonixR oral Zollinger-Ellison Syndrome (U.S.)※削除(前年Regulatory review) rPSGL-Ig Acute coronary syndrome/acute myocardial infarction※削除(前年P2) ★Immunology and Oncology CCI-779 Renal cell carcinoma※P2(前年P3) Breast cancer※P2(前年なし) Various solid tumors※削除(前年P2) MylotargR Induction/consolidation in acute myeloid leukemia※削除(前年P2) RapamuneR Conversion in liver transplant※P3(前年同) Conversion in renal transplant※P3(前年同) Maintenance regimen in renal transplant (U.S.)※Regulatory review(前年同) Pediatric usage※P3(前年同) rhIL-11 Oral therapy in inflammatory bowel disease※P2(前年同) ★Hemophilia ReFactoR AF Hemophilia A※P3(前年同) ●2002年度売上4％増加 ワイス、2002年度第4四半期および通年業績を発表[2003.2.12] 全世界における医療用医薬品の売上＄11,733,261千ドルは、前年同期と比較し、2002年度 通年で７％増加。2002年度通年の売上増加要因は、中高年女性用ホルモン製剤「Premari n」関連製品や、第4四半期における抗不整脈薬「Cordarone I.V.」（米国商品名）、さら に通年での｢Prevnar｣等の売上減により一部相殺されたものの、抗うつ剤「EffexorXR」 (米国商品名)、逆流性食道炎(GERD)治療剤「Protonix」(米国商品名) などの売上が好調 であったことがあげられます。 ●アメリカン･ホーム･プロダクツ(AHP)2001年第4四半期および2001年通期業績を発表[2002.2.5] 2001年通期業績 継続事業の利益は、前年の9億100万ドルの赤字から22億8,530万ドルの黒字、希薄化後一 株利益は、前年同期の0.69ドルの損失から1.72ドルの黒字となりました。 2000年および2001年の業績におけるダイエット薬訴訟費用などの特殊要因を除き、2000年 の希薄効果を加味した普通株式として評価した2001年通期の継続事業の利益は、前年25億 1,400万ドルから15％増の29億30万ドル、希薄化後一株利益は、前年1.90ドルから15％増の2.18ドルとなりました。 ロバート・エスナー社長兼最高経営責任者（CEO）は、｢2001年第4四半期および通期は当 社史上最も高い営業利益を達成でき、非常に満足しています。2001年度は、プレマリン製 品群の売上は20億ドルに達し、エフェクサーはAHP製品の中で最も速く15億ドルの売上げ を達成しました。こうした結果は、当社が短期、長期双方の目標の実現に向けて順調に前 進していることを示しています。｣と述べています。
($000) 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 備考 Effexor 3,927,856(+3.5) 3,793,904(+1.9) 3,722,052(+7.6) 3,458,835(+3.3) 3,347,369 2,711,706(+30.8) 2,072,316(+34.4) 1,542,016(+33.04) 1,159,088(+48.46%) 780,755 [venlafaxine]/[米特許]2008迄;海外名Efexor 米国内 2,686,868(+4.3) 2,577,062(+6.5) 2,419,514(+6.3) 2,275,121(+0.5) 2,264,199 1,864,780(+28.6) 1,449,975 米国外 1,240,988(+2.0) 1,216,842(-6.6) 1,302,538(+10.0) 1,183,714(+9.3) 1,083,170 846,926(+36.1) 622,429 2001.5 うつ病再発予防FDA承認、2001.Social anxiety disorder申請 Protonix米国内 394,871(-79.3) 1,911,247(+6.5) 1,795,011(+6.5) 1,684,903(+5.9) 1,590,604 1,493,299(+39.5) 1,070,804(+90.8) 561,261(287.07) 145,002(+100) --- pantoprazole;PPI 米国のみ/[米特許]2010迄 Protonix Generic米国内 411,569(-) - Prevnar 2,715,507(+11.3) 2,439,056(+24.4) 1,961,325(+30.0) 1,508,259(+43.1) 1,053,629 945,646(+46.0) 647,528(-18.9) 798,210(+73.30) 460,586(+100) 00.1Q発売 Pneumococcal vaccine/[米特許]2007迄;海外名PREVENAR 米国内 1,180,062(+3.5) 1,140,462(+11.1) 1,026,433(+4.6) 981,334(+36.5) 718,772 769,340(+34.3) 572,969 米国外 1,535,445(+18.2) 1,298,594(+38.9) 934,892(+77.4) 526,925(+57.4) 334,857 176,306(+136.5) 74,559 Enbrel 米国外 2,592,918(+26.8) 2,044,628(+36.3) 1,083,661(+38.4) 1,083,661(+59.4) 679,980 298,880(+88.2) 158,805(+69.2) 93,851(+149.33) 37,641(362.59) 8,137 etanercept*米加以外のみ,2002全$856m(+24)
Psoriatic arthritis (2002.1 FDA承認, EU 2001後半申請)/[米特許]2012迄ENBREL ALLIANCE REVENUE 1,204,672(+20.5) 999,761 米国内 1,134,741(+20.6) 940,614 米国外 69,931(+18.2) 59,147 栄養剤 1,633,901(+13.2) 1,443,034(+20.2) 1,200,814(+15.4) 1,040,922(+10.4) 943,255 857,576(+2.7) 834,725(+1.4) 823,536(+5.84) 690,794(-0.73) 695,848 *主に米国外 米国内 4,,352(+23.8) 3,514(-16.0) 4,184(-36.0) 6,538(-89.3) 61,053 63,026(+32.2) 47,672 米国外 1,629,549(+13.2) 1,439,520(+20.3) 1,196,630(+15.7) 1,034,384(+17.3) 882,202 794,550(+1.0) 787,053 Premarin群計 1,070,401(+1.4) 1,055,337(+0.4) 1,050,860(+15.6) 908,887(+3.3) 880,181 1,275,347(-32.2) 1,879,860(-9.3) 2,073,525(+10.87) 1,870,221(+5.3) 1,776,144 HRT;結合estrogen 米国内 965,897(+1.8) 948,668(+1.2) 937,155(+20.8) 776,064(+7.9) 718,911 1,072,437(-33.5) 1,613,825(-10.1) 1,795,558 米国外 104,504(-2.0) 106,669(-6.2) 113,705(-14.4) 132,823(-17.6) 161,270 202,910(-23.7) 266,018(-4.3) 277,967 Premarin 812,320(+0.0) 811,994(+21.7) 667,005(+1.2) 658,795 983,794(-20.9) 1,243,522(+4.9) 1,185,640 米国内 732,355(+0.0) 732,330(+26.8) 577,758(+3.1) 560,539 872,712(-21.0) 1,104,836(+5.6) 1,045,898 米国外 79,965(+0.4) 79,664(-10.7) 89,247(-9.2) 98,256 111,082(-19.9) 138,686(-0.8) 139,742 Prempro/phase 243,017(+1.7) 238,866(-1.2) 241,882(+9.3) 221,386 291,553(-54.2) 636,321(-28.3) 887,885 /[米特許]2015迄 米国内 216,313(+5.6) 204,825(+3.3) 198,306(+25.2) 158,372 199,725(-60.8) 508,989(-32.1) 749,660 米国外 26,704(-21.6) 34,041(-21.9) 43,576(-30.8) 63,014 91,828(-27.9) 127,332(-7.9) 138,225 Zosyn/Tazocin 1,264,036(+11.2) 1,137,193(+17.0) 971,994(+9.0) 891,573(+17.3) 760,288 638,671(57.3) 406,079(-7.7) 426,882(+11.02) 384,512(+16.1%) 315,701 [tazobactam+PIPC]/[米特許]2007迄;米国内ZOSYN国際TAZOCIN 米国内 701,105(+21.8) 575,775(+16.7) 493,467(+7.2) 460,159(+16.5) 355,313 355,313(+70.6) 208,247 米国外 562,931(+0.3) 561,418(+17.3) 478,527(+10.9) 431,414(+18.1) 365,334 283,358(+43.2) 197,830 OC 385,969(-11.0) 433,854(-4.6) 454,908(-13.4) 525,326(-11.0) 590,138 589,190(+2.2) 576,299(-18.1) 562,578(-7.85) 610,163(-5.31%) 644,381 ORAL CONTRACEPTIVES (excluding Alesse) 米国内 42,459(-16.3) 50,740(-11.9) 57,597(-34.7) 88,149(-24.4) 116,600 138,285(-23.3) 180,278 米国外 343,510(-10.3) 383,114(-3.6) 397,311(-9.1) 437,177(-7.7) 473,538 450,905(+13.9) 396,022 ZOTON 130,829(-65.2) 375,740(-16.1) 447,700 363,185(+17.4) 309,404(+8.9) 284,061(+21.47) 233,858(12.17) 208,469 lansoprazole*米国外のみ BeneFIX 586,862(+35.6) 432,646(+21.0) 357,623(+4.2) 343,259(+13.8) 301,508 248,071(+13.2) 219,220(+3.0) 212,796(+18.19) 180,043(18.25) 152,255 Factor IX/[米特許]2011迄 米国内 262,818(-3.9) 273,541(-10.0) 304,005(+2.5) 296,554(+13.3) 261,787 218,397(+10.5) 197,605 米国外 324,044(+103.7) 159,105(+196.7) 53,618(+14.8) 46,705(+17.6) 39,721 29,674(+37.3) 21,615 Rapamune 375,795(+3.0) 364,765(+8.3) 336,883(+12.2) 300,202(+15.9) 259,040 169,758(+30.8) 129,737(+84.9) 70,185(+165.35) 26,450(875.65) 2,711 sirolimus/[米特許]2009迄,延長2013可 米国内 190,876(+0.9) 189,134(+0.7) 187,763(+9.1) 172,047(+7.8) 159,666 101,726(+5.3) 96,602 米国外 184,919(+5.3) 175,631(+17.8) 149,120(+16.4) 128,155(+29.0) 99,374 68,032(+105.3) 33,135 ReFacto/XYNTHA 363,254(+8.5) 334,857(+9.6) 305,626(+13.9) 268,411(+7.6) 249,379 224,173(+13.5) 197,549(+34.2) 147,259(+61.67) 91,085(+164.78) 34,400 Antihemophilic Factor/[米特許]2010迄 米国内 73,677(+0.3) 73,428(+12.9) 65,035(+17.4) 55,380(+26.6) 43,737 44,811(+2.4) 43,744 米国外 289,577(+10.8) 261,429(+8.7) 240,591(+12.9) 205,642(+3.6) 205,642 179,362(+16.6) 153,805 rhBMP-2 389,621(+8.6) 358,886(+16.5) 307,940(+30.5) 236,291(+43.0) 165,279 58,100 66,500 /[米特許]2014迄;骨形成誘導 米国内 376,426(+7.4) 350,572(+15.4) 303,905(+29.4) 234,802(+42.8) 164,449 57,939 米国外 13,195(+58.7) 8,314(+106.0) 4,035(+171.0) 1,489(+79.4) 830 161 Tygacil 216,184(+56.8) 137,906(+92.8) 71,516 10,004 [tigecycline]静注抗生物質；腹腔内感染または複雑性皮膚・皮膚組織感染症の治療薬として2005.3 FDA承認 米国内 132,531(+36.2) 97,277(+60.3) 60,680 9,905 米国外 83,653(+105.9) 40,629(+274.9) 10,836 99 Torisel 122,117(+359.2) 26,593 [tensirolimus]腎細胞癌;米承認2007.5/欧承認2007.11 米国内 82,292(+216.2) 26,028 米国外 39,825(-) 565 Pristiq米国内 66,512(-) - [desvenlafaxine]うつ病;米承認2008.2.29 小計 17,722,045(+4.8) 16,913,667
旧15,887,313(+13.2)14,166,949(+12.1) 12,626,269(+12.1) 11,268,358 米国内 8,707,056(-4.9) 9,158,062
旧8,191,420(+7.0)7,654,749(+8.7) 7,031,051(+8.3) 6,494,732 米国外 9,014,989(+16.2) 7,755,605
旧7,695,893(+20.6)6,512,200(+16.4) 5,595,218(+17.2) 4,773,626 ●他の医薬品 計 1,303,385(-23.7) 1,708,316
旧1,440,474(-4.5)1,378,024(-10.4) 1,548,354(-18.8) 1,905,893 米国内 209,027(-60.3) 525,988
旧315,190(-0.3)316,198(-14.7) 380,704(-43.9) 678,564 米国外 1,094,358(-7.4) 1,182,328
旧1,125,284(-5.6)1,061,826(-9.0) 1,167,570(-4.9) 1,227,329 ALESSE - - - - ? ? 140,834(+9.99) 128,046(37.44) 93,167 [norgestrel+EE]国際ブランド名=LOETTE Cordarone I.V. - - - - ? 283,204(+5.0) 269,603(+32.71) 203,157(+5.67) 192,257 amiodarone ATIVAN - - - 198,355 211,454(-2.7) 217,231(-6.6) 232,662(-5.46) 246,098(-3.21%) 254,258 lorazepam 抗不安 米国内 - - - 8,834 17,362(-59.8) 43,144 米国外 - - - 189,521 194,092(+11.5) 174,087 SYNVISC - - 10,600 197,484 222,614(+4.8) 212,458(+12.8) 188,277(+5.02) 179,269(43.94) 124,547 Hylan G-F20 米国内 - - - 179,262 205,148(+5.9) 193,687 米国外 - - - 18,222 17,466(-6.5) 18,682 MINOCIN - - - - 117,124(-4.1) 122,127(-17.02) 147,174(4.95) 140,234 minocycline FACTOR VIII - - - - ? ? 129,195(+43.92) 89,767(-43.09) 157,727 米国のみ LODINE - - - - ? ? ? 79,241(-49.7) 157,543 [etodolac] SONATA - - - - - [Elanに譲渡] 88,818(+20.1) 73,951(+110.15) 35,190 zaleplon 睡眠障害 NEUMEGA - - - - ? ? 29,139(-13.96) 33,866(-15.03) 39,856 oprelvekin MYLOTARG - - - - ? ? 30,125(+49.19) 20,193(+100) --- [gemtuzumab ozogamicin]米国のみ;再発性・難治性骨髄性白血病の治療薬 Flumist - - - - 15,249(-) - - - 2003発売 Influenza vaccine 米国のみ Generic - - - 164,449 57,939 187,400 309,800 444,600 --- Meningitec - - - - ? 90,100 78,610(-75.63) 322,575(+559.04) 48,946 *米国外のみ(髄膜炎菌グループC病用結合ワクチン) ZIAC/Zeta - - - - ? 64,100 69,886(-75.37) 283,698(4.16%) 244,936 bisoprolol Alliance収入 1,294,196(-3.4) 1,339,217(+16.8) 1,146,503(+45.2) 789,900 654,400 418,800 米国内 1,177,440(-1.8) 1,198,717(+17.4) 1,021,087(+41.2) 723,072 米国外 116,756(-16.9) 140,500(+12.0) 125,416(+87.8) 66,787 その他 - - - 1,509,900 1,660,500 2,128,700 ●Wyeth医薬合計 19,025,430(+2.2) 18,621,983(+10.3) 16,884,190(+10.2) 15,321,126(+9.7) 13,964,110 12,622,700 11,733,300 米国内 8,916,083(-7.9) 9,684,050(+5.6) 9,169,664(+8.7) 8,432,922(+6.8) 7,896,368 米国外 10,109,347(+13.1) 8,937,933(+15.9) 7,714,526(+12.0) 6,888,204(+13.5) 6,067,742 Fort Dodge 1,087,922(+4.4) 1,041,731(+11.3) 936,297(+6.3) 880,766(+5.3) 836,532 米国内 406,140(-9.0) 446,210(+7.9) 413,376(+5.1) 393,493(-0.5) 395,381 米国外 681,782(+14.5) 595,521(+13.9) 522,921(+7.3) 487,273(+10.5) 441,151 ●医薬品 合計 19,663,714(+10.3) 17,820,487(+10.0) 16,201,892(+9.5) 14,800,642 米国内 10,130,260(+5.7) 9,583,040(+8.6) 8,826,415(+6.4) 8,291,749 米国外 9,533,454(+15.7) 8,237,447(+11.7) 7,375,477(+13.3) 6,508,893 ADVIL群 673,269(-1.6) 684,099(+10.3) 620,164(+13.8) 636,440(+2.6) 620,101 604,300 米国内 483,915(-5.8) 513,812(+8.8) 472,216(+13.7) 473,360(-1.3) 479,455 米国外 189,354(+11.2) 170,287(+15.1) 147,948(+14.4) 163,080(+16.0) 140,646 CENTRUM 727,965(+3.3) 704,895(+7.3) 657,052(+3.6) 633,978(+2.8) 616,632 545,600 米国内 323,666(-2.8) 332,842(-3.5) 344,859(+1.4) 339,954(-5.3) 358,973 米国外 404,299(+8.7) 372,053(+19.2) 312,193(+6.2) 294,024(+14.1) 257,659 ROBITUSSIN 198,719(-9.8) 220,341(-2.3) 225,541(-10.9) 253,194(+6.4) 237,939 230,300 米国内 139,678(-15.9) 166,090(-8.4) 181,237(-14.6) 212,345(+5.2) 201,803 米国外 59,041(+8.8) 54,251(+22.5) 44,304(+8.5) 40,849(+13.0) 36,136 CALTRATE 249,208(+10.3) 225,871(+15.8) 195,099(+3.1) 189,213(+5.7) 178,954 153,400 米国内 75,309(+3.1) 73,030(+13.3) 64,480(-7.5) 69,707(-3.4) 72,186 米国外 173,899(+13.8) 152,841(+17.0) 130,619(+9.3) 119,510(+11.9) 106,768 CHAPSTICK 137,573(-1.6) 139,747(+9.2) 127,939(-4.8) 134,367(+9.0) 123,216 113,900 米国内 109,569(-2.7) 112,652(+3.2) 109,119(-4.7) 114,541(+9.5) 104,635 米国外 28,004(+3.4) 27,095(+44.0) 18,820(-5.1) 19,826(+6.7) 18,581 PREPARATION H 111,735(+1.8) 109,712(+6.4) 103,096(-1.7) 104,853(+2.5) 102,303 92,300 米国内 87,308(+2.2) 85,454(+2.4) 83,415(+1.1) 82,538(+7.6) 76,717 米国外 24,427(+0.7) 24,258(+23.3) 19,681(-11.8) 22,315(-12.8) 25,586 ADVIL COLD & SINUS 71,845(-2.5) 73,674(+20.8) 61,010(-33.4) 91,658 [] 米国内 29,948(-9.4) 33,039(+22.2) 27,047(-53.3) 57,905 米国外 41,897(+3.1) 40,635(+19.6) 33,963(+0.6) 33,753 THERMACARE 26,470 - 米国内 20,510 - 米国外 5,960 - DIMETAPP - - - 80,359(-8.5) 87,843 85,200 米国内 - - - 43,039(-12.8) 49,356 米国外 - - - 37,320(-3.0) 38,487 SOLGAR - - - 58,472(-44.6) 105,462 105,100 米国内 - - - 28,089(-45.5) 51,506 米国外 - - - 30,383(-43.7) 53,956 ALAVERT - - - 49,468(-11.6) 55,974 81,600 米国内 - - - 49,465(-11.6) 55,974 米国外 - - - 3(-) - 他の消費者向け保健製品 523,772(-9.3) 577,745(+6.9) 540,267(-10.2) 413,550(-3.6) 428,962 441,500 米国内 122,498(-35.7) 190,505(+0.8) 189,003(-16.0) 104,349(-8.6) 114,154 米国外 401,274(+3.6) 387,240(+10.2) 351,264(-6.8) 309,201(-1.8) 314,808 ●消費者向け保健製品 計 2,720,556(-0.6) 2,736,084(+8.1) 2,530,168(-0.9) 2,553,898(-0.1) 2,557,386 2,434,500 米国内 1,392,401(-7.6) 1,507,424(+2.4) 1,471,376(-3.0) 1,517,387(-3.0) 1,564,759 米国外 1,328,155(+8.1) 1,228,660(+16.0) 1,058,792(+2.1) 1,036,511(+4.4) 992,627 ●総合計 22,833,908(+1.9) 22,399,798(+10.1) 20,350,655(+8.5) 18,755,790(+8.1) 17,358,028 米国内 10,714,624(-7.9) 11,637,684(+5.3) 11,054,416(+6.9) 10,343,802(+4.9) 9,856,507 米国外 12,119,284(+12.6) 10,762,114(+15.8) 9,296,239(+10.5) 8,411,988(+12.1) 7,501,520 米国内 米国外
●ＡＨＰの００年度全世界売上高、１２％増 日本ワイスレダリー
薬事日報01/04/25 日本ワイスレダリーの二十日付ニュースリリースによると、親会社であるアメリカン・ホーム・プロダクツ社（ＡＨＰ）の二〇〇〇年度の全世界売上高は、一三二億六三〇〇万ドルに達し前年度比一二％増を記録した。同年度の継続事業による利益は二五億一四〇〇万ドル、一八％増。ホルモン補充療法に使われるプレマリン製品グループ（一九億ドル）、抗うつ剤エフェクサー製品グループ（前年度比四八％増の一二億ドル）、抗リウマチ薬エンブレル（六億九〇〇〇万ドル）などが貢献した。
ＡＨＰは今年で創立七十五周年を迎えたが、昨年六月には農業製品事業から撤退、医薬品、消費者向けヘルスケア製品、動物薬の三事業部門に完全に特化することとなった。特に医薬品の売上構成比は十年前の五一％から八一％へと拡大成長している。
研究開発投資は一七億ドル。九九年六月～〇〇年五月にかけて、七つもの大型医薬品・ワクチン（髄膜炎菌グループＣ病用結合ワクチンMeningitec、肺炎球菌結合ワクチンPrevnar、びらん性食道炎治療剤Protonix、Ａ型血友病治療剤ReFacto、再発性急性骨髄性白血病治療剤Mylotarg、心疾患用ＡＣＥ阻害剤Altace、希釈インフルエンザ・ワクチンFluMist）の承認を取得しており、年間承認取得数は業界最高としている。
化学合成品（スモールモレキュール）、生物学的製剤（バイオ）、ワクチンの三分野を研究開発重点領域とし、特にバイオテクノロジーに関しては、セレラ・ジェノミクスグループやインサイト・ジェノミクス社との提携などが行われている。
また、生産面でも能力向上のため五年間で二〇億ドルが投資されている。製造設備は五大陸にまたがる。世界関連会社の従業員は四万八〇〇〇人。●AHPの2000年度業績総収益12%増の132億6,300万ドルを達成
アメリカン・ホーム・プロダクツ・コーポレーション(以下AHP)は、2000年度の業績を発表した。 2000年度の全世界の総収益は132億6,300万ドルであり、1999年度の118億8,100万ドルにくらべ12%増を記録した。これは主として、ホルモン補充療法に使われるプレマリン製品グループ(19億ドル)、エフェクサー製品グループ(抗うつ剤、前年度比48%増の12億ドル)、エンブレル(抗リウマチ薬、6億9,000万ドル)などの医薬品が全世界で好調な売上げを記録したことによるものである。 一方、ワーナー・ランバート社との合併解消に伴う違約金や、ダイエット薬訴訟に伴う諸費用など非正常項目を除く2000年度の継続事業による利益は、25億1,400万ドルであり、1999年度の21億3,300万ドルに比べ18%増加した。AHPは1926年の会社創業以来、創立75周年を迎え、研究開発型製薬企業として世界的リーダーに発展しつつある。2000年6月には農業製品事業からの撤退により、医薬品、消費者向けヘルスケア製品、動物薬の3事業部門に完全に特化することになった。とくに医薬品事業のグローバルな展開により、医薬品の全社売上構成比は10年前の51%から81%へと拡大成長を遂げている。
AHPは2000年度17億ドルの研究開発投資を行った。その結果、AHPの専門医薬品部門であるワイス・エアスト社では、1999年6月から2000年5月にかけて、7つの大型医薬品・ワクチンの承認取得を獲得した。この年間承認取得数は業界最高記録である。
・Meningitec(髄膜炎菌グループC病用結合ワクチン) ・Prevnar(肺炎球菌結合ワクチン) ・Protonix(びらん性食道炎治療剤) ・ReFacto(A型血友病治療剤) ・Mylotarg(再発性急性骨髄性白血病治療剤) ・Altace(心疾患用ACE阻害剤) ・FluMist(希釈インフルエンザ・ワクチン) また研究開発だけでなく、生産能力向上のため5年間で20億ドルの投資を行うとともに、C elera Genomics GroupおよびIncyte Genomics Inc.との提携によりバイオテクノロジー関 連分野でも製薬企業最大手のひとつに数えられている。
●医療用医薬品 【2008】
The Pharmaceuticals segment develops, manufactures, distributes and sells branded human ethical pharmaceuticals, biotechnology products, vaccines and nutritional products. These products are promoted and sold worldwide primarily to wholesalers, pharmacies, hospitals, governments, physicians, retailers and other human health care institutions. Some of these sales are made to large buying groups representing certain of these customers. Product categories and their respective products include: neuroscience therapies, including EFFEXOR and EFFEXOR XR (marketed as EFEXOR and EFEXOR XR internationally) and PRISTIQ; vaccines, including PREVNAR (marketed as PREVENAR internationally); musculoskeletal therapies, including ENBREL (co-promoted in the United States and Canada with Amgen, Inc. (Amgen)); nutritional products, including S-26 GOLD, PROGRESS GOLD and PROMIL GOLD (international markets only); gastroenterology drugs, including PROTONIX and generic pantoprazole (United States market only); anti-infectives, including ZOSYN (marketed as TAZOCIN internationally) and TYGACIL; oncology therapies, including TORISEL; hemophilia treatments, including BENEFIX Coagulation Factor IX (Recombinant), REFACTO albumin-free formulated Factor VIII (Recombinant) and XYNTHA/REFACTO AF (the European Union (EU) trade name for XYNTHA); immunological products, including RAPAMUNE; and women's health care products, including PREMARIN and PREMPRO. We manufacture these products in the United States and Puerto Rico, and in 13 other countries.Sales of EFFEXOR and EFFEXOR XR were 17%, 17% and 18% of net revenue for 2008, 2007 and 2006, respectively. Sales of ENBREL, including the alliance revenue recognized from a co-promotion agreement with Amgen for the United States and Canada, were 17%, 14% and 12% of net revenue for 2008, 2007 and 2006, respectively. Sales of PREVNAR were 12% and 11% of net revenue for 2008 and 2007, respectively. Except as noted above, no other single Pharmaceuticals product accounted for more than 10% of net revenue in 2008, 2007 or 2006.
●Wyeth －http://www.wyeth.com/ 2002.3.11 American Home Products[US]は、Wyeth(ワイス)に社名変更。 see History 尚、2001.12 同社が大株主のImmunexがAmgenにより買収。 ●Press Releases ●Our Products Lybrel(TM) (90 mcg levonorgestrel and 20 mcg ethinyl estradiol) Tablets Women's Health Product Overview Prescribing Information Download the prescribing information for LYBREL. Download the patient labeling (PPI) for LYBREL. Press Release Read the LYBREL press release at Wyeth.com ●Investor Relations ★Financial Reports 2008 Annual Review - - Product Net Sales Reports 4Q 2008 2007 Annual Review - [PDF] 2007 Financial Report 4Q 2007 Net Revenue Report 2006 Annual Review (Interactive Format) - [pdf] 2006 Financial Report (Interactive Format) - [pdf] Product Net Sales Reports - 4Q 2006 Net Revenue Report 4Q 2005 Net Revenue Report 2005 Annual Report (Interactive Format) 2005 Annual Review 4Q 2004 Net Revenue Report -Product Net Sales Reports;個別製品売上高 2004 Annual Report (Interactive Format) 2004 Annual Report (PDF Format) [pdf,88p] ★Annual Reports なお全個別製品売上は上記の第４四半期報告に含む。*一部Minor製品は年報 Special announcements Wyeth Reports Earnings Results for the 2006 Fourth Quarter and Full Year[2007.1.30] Wyeth Reports Earnings Results for the 2005 Fourth Quarter and Full Year[2006.1.31] Wyeth Reports Results for the 2004 Fourth Quarter and Full Year[2005.1.31,pdf,21p] 4Q 2003 Net Revenue Report[1/22/2004] 4Q 2002 Net Revenue Report 4Q 2001 Net Revenue Report ★SEC Filings 10-K Annual report[2009.2.27] - [pdf,310p;copy不可] - [doc] - [xls] 10-K Annual report[2008.2.29] - [pdf] - [doc] - [xls] 10-K Annual report[2007.2.26] - [PDF] 10-K Annual report[2006.2.27] - [pdf,220p] - [xls] 10-K Annual report[2005.3.14] - [pdf,192p] ★Investor News ●http://www.vaccine-worldinfo.com/ --- Wyethワクチン製品サイト(要ID)
●ワイス株式会社 http://www.wyeth.jp/; 2003.12.1現社名に変更。 [旧]日本ワイスレダリー アメリカン･ホーム･プロダクツ(AHP)社名変更:3月より社名を『Wyeth』に[2002.2.1] --- 日本ワイスレダリ－株式会社の米国親会社、American Home Products(AHP:アメリカ ン・ホーム・プロダクツ)は本年3月11日付けをもって、社名を『Wyeth』(ワイス)に変更することになりました。 ワイスと武田薬品との新たな提携について[2003.5.21] - ワイス（本社：米国ニュージャージー州マディソン、会長、社長兼ＣＥＯ：ロバート・エスナー）と武田薬品工業株式会社（本社：大阪市中央区、社長：武田國男）は、本 日、武田薬品が保有する 日本ワイスレダリー社の株式譲渡、関節リウマチ治療薬「エタ ネルセプト」（米国製品名 エンブレル）のコ・プロモーションなどを含む新たな提携を スタートさせることについて合意いたしました。また、日本ワイスレダリー株式会社はワ イス株式会社に社名変更いたします。 2009.06.18 あすか製薬がワイス株式会社からの製品承継 あすか製薬株式会社は、ワイス株式会社が製造販売、武田薬品工業株式会社が販売する下記5製品の譲渡を受けることとなった。 平成21年7月1日からワイスに代わりあすか製薬が製品の供給と医薬情報活動を継続する。 なお、「ノバントロン注」は日本製薬株式会社に医薬情報活動を委託。 １．経口避妊剤「トライディオール21錠、トライディオール28錠」 ２．黄体・卵胞ホルモン配合剤「プラノバール配合錠」 ３．非ステロイド性鎮痛・抗炎症剤「オステラック錠100、オステラック錠200」 ４．睡眠導入剤「ロラメット錠1.0」 ５．アントラキノン系抗悪性腫瘍剤「ノバントロン注10mg、ノバントロン注20mg」 ●プレスリリース ワイス 2008年通年および第4四半期の業績を発表[2009.2.10] ●開発品リスト ヘルスケア～女性、関節炎、感染症、癌 ●製品情報[医療関係者のページ] 関節リウマチ（ＲＡ）の総合ウェブサイト「リウマチｅネット」 http://www.riumachi.jp/ - 2003.2.24開設
●日本ワイスレダリー株式会社 2002年度決算 売上高7.5％増、利益43.7％増[2003.4.1]
日本ワイスレダリー(以下WLJ)の2002年度全社売上高は、前年度（2001年１月～2001年12月期）の実績を約35億円（7.5%）上回る497億円に達しました。
製品別売上では、経皮吸収型鎮痛消炎剤「セルタッチ」(2.0％増)が伸び悩んだものの、1999年に発売した活性型葉酸製剤「アイソボリン」(42.4％増)、抗リウマチ剤「リウマトレックス」(42.1％増)、明治製菓への注射用カルバペネム系抗菌剤「オメガシン」を始めとする第三者への販売により前年度を上回る実績を上げることができました。
税引前利益においても、前年実績を19億円（38.0％）上回る68億円を達成しました｡これは、主に粗利益率の高いアイソボリンとリウマトレックスの売上増によるものです。●日本ワイスレダリー株式会社2001年度決算[2002.4.10]
業績の概要
日本ワイスレダリー(以下WLJ)の2001年度全社売上高は、前年度（1999年12月～2000年11月期）の実績に比べ、37億円上回り、8.8％の伸びを示しました。
製品別売上げでは、1999年に発売した活性型葉酸製剤「アイソボリン」(72.5％増)、抗リウマチ剤「リウマトレックス」(60.3％増)、経口避妊剤「トライディオール」(86.6％増)の顕著な貢献に加え、競争が激化している 抗炎症剤市場においても、非ステロイド性鎮痛・抗炎症剤「オステラック」(8.6％増)、経皮吸収型鎮痛消炎剤「セルタッチ」(7.0％増)が前年度を上回る実績を上げることができました。
ＷＬＪは、新製品開発の推進および2003年から2004年に予定されている新製品の上市を、中期的な経営戦略の核と考えております。この中には期待のリウマチ治療薬も含まれており、その他抗うつ薬などの新製品導入により、早い時期に売上げ1,000億円（薬価ベース）を達成し、業界順位で20位にランクイン（2001年度37位）することをめざしています。
一方、利益面では、税引前利益が前年実績を12億円(31.1％)上回る49.3億円、税引き後の当期利益が前年実績を７億円(39.0％)上回る25.5億円と、好業績を示しました。この要因は、アイソボリンとリウマトレックスの大幅な売上増により、前年度に引続き利益率を改善することができたことによるものです。開発品リスト
(2006.3.7)他、開発候補及び開発着手品18品目 ●「開発品リスト」からの除外製品
開発品目 一般名 適応症 剤形 段階 備考 WY-45,030 エフェクサー venlafaxine 抗うつ薬 カプセル P3 米国で承認 自社品、50ヶ国以上で承認済 Prevenar(7vPnCV) ７価肺炎球菌ワクチン 肺炎球菌由来の感染症の予防 注射剤 P2 米国で承認 自社品，66ヶ国で承認済み TSE-424 bazedoxifene 閉経後骨粗鬆症治療薬 カプセル P2 米国で第Ⅲ相 エンブレル皮下注用25mg
(TNR－001)etanerceptエタネルセプト [追加適応]若年性リウマチ 皮下注射 第Ⅱ相 米国で承認 自社品，日本他67ヶ国で承認済み
開発品目 一般名 適応症 剤形 段階 備考 CMA-676 マイロターグ gemtuzumab ozogamicin 急性骨髄性
白血病治療薬静脈内注射 発売05.9.22 Premarin/MPA conjugated estrogens/
medroxyprogesterone
acetate骨粗鬆症治療薬 錠剤 P3 エンブレル皮下注用25mg
(TNR－001)etanerceptエタネルセプト リウマチ治療薬 皮下注射 発売
05.3.302002.11申請単独 Leucovorin/UFT
ロイコボリン25mg錠folinate calcium 大腸がん治療薬 錠剤 申請 01.10申請・大鵬薬品共同
03.3Q市販予定L-846 zaleplon 睡眠導入薬 カプセル X 前期P3/今期削除
■Vicuron Pharmaceuticals,Inc.
- http://www.vicuron.com/; 従業員数 246人うちPh.D./M.D. 66人(2003年末)。 年間総収入(2003) $9.6 million、 損失$174 million (2003) 新薬開発前のため。 1995 Sepracor Inc.の100%子会社としてVersicor Inc.設立。 anidulafungin and dalbavancin等抗菌剤の研究開発。 2000.8 株式公開。 2003.2.28 Biosearch Italia S.p.A[イタリア]を買収。 2003.6.30 Vicuron Pharmaceuticals Italy S.r.1. に社名変更。 2003.3. Vicuron Pharmaceuticals,Inc.に社名変更。 2005.6 Pfizer Incにより買収。(2005.9.14合併完了) 抗生物質ramoplanin P3 に関して、Genome Therapeutics Corporationは、 北米はVicuron Pharmaceuticalsにライセンス。
●Vicuron Pharmaceuticals,Inc. ●News[PR Newswire] ●SEC Information 10-K Annual Report (2005.3.16) ★Anidulafungin 抗真菌剤 Eraxis Full U.S. Prescribing Information (2003初P3完了、2004.1 FDAへ資料提出、2004.5.25迄にNDA審査結果待ち),2003.12 EMEA申請 ★Dalbavancin グラム陽性菌抗生物質 Zeven (dalbavancin;BI397) - a teicoplanin analog (2004.12.21 FDA申請、適応症は複合皮膚・結合組織感染症(cSSTIs). ) ３つのPhase 3研究(MRSA400例を含む1,850症例)により評価される。
■Pharming NV[蘭]
1995年創立のbiotech企業 as a spin-off from GenPharm Intl. ●会社決算
(Eur milllion) 2009 2008 2007 2006 2005 収入 1.096 0.664 0.7 営業費用 (28.944) (30.131) (25.3) 営業利益 (27.848) (29.467) () 当期純利益 (32.060) (26.205) (21.6) 研究開発費 24.525 22.085 従業員数[連結]
●conestat alfa(Ruconest(TM)[Pharming NV] ) 【2009】harming's lead product candidate, Rhucin@�, is the therapeutic protein recombinant human C1 inhibitor (rhC1INH) for treatment of acute attacks of HAE, a genetic disorder. The Company also develops applications of rhC1INH in the area of organ transplantation. In addition, the Company pursues the development, internally or externally, of other products in its pipeline, including recombinant human fibrinogen (rhFIB), human lactoferrin (hLF) and recombinant human collagen (rhCOL), mainly through strategic alliances and partnerships with interested parties. As a result of the progress through the regulatory evaluation process of Rhucin/rhC1INH, Pharming is seeking to lower its financial risk profile by focusing on the commercialisation of Rhucin/rhC1INH for HAE and its subsequent development in follow-on indications, such as antibody-mediated rejection (AMR) and delayed graft function (DGF).
The Company's lead product candidate, Rhucin, is the therapeutic protein rhC1INH for treatment of acute attacks of HAE, a genetic disorder. These attacks are characterised by acute painful and in some cases fatal swellings of soft tissues (edema), including regions of the skin, abdomen and the mouth and throat. Untreated HAE-attacks may last up to five days. Pharming filed a MAA for Rhucin with the EMA in 2006. In March 2008, Pharming received a negative opinion regarding its MAA. Based on the feedback of the EMA, Pharming has expanded the dossier on Rhucin substantially. By June 2009, over 400 administrations of Rhucin were analysed, with more than half of them repeat treatments (up to as much as twenty five repeat treatments per patient). There was no sign of any relevant safety issues in these repeat treatments, nor of induction of allergies and the efficacy was confirmed to be very good. Pharming has submitted a new MAA for Rhucin to the EMA on 3 September 2009 and expects to receive the final opinion from the EMA by the end of June 2010.
Pharming has entered into three commercial agreements for the development, marketing and sales of Rhucin for treatment of acute attacks of HAE in Europe. The most recent contract was concluded with Swedish Orphan in April 2010.
Pharming is also preparing for submission of its market authorisation file (BLA) of Rhucin in the United States and is currently in pre-BLA discussions with the FDA. The Company initiated the pre-BLA process with the FDA early December 2009. Pharming expects to provide further updates on the upcoming BLA filing timelines in the United States during the first half of 2010.
Pharming is also developing rhC1INH for the treatment of AMR and DGF in kidney transplantation. Despite all the technical advances that have been made during the last decades, rejection of transplanted organs remains a critical issue. Given the shortage of available organs and the high costs associated with transplantation, there is a need for additional new and safe products that reduce the chances of organ rejection. There is significant scientific evidence that rhC1INH can be used to prevent complications after organ transplantation. The Company is preparing the start of Phase II studies of rhC1INH in both AMR and DGF in kidney transplantation in the course of 2010
●Pharming NV[蘭] ●Products ■Investor Relations ●Press Releases Pharming Announces 2009 Results[2010.2.18] ●Presentation kﾎPresentation Pharming full year 2009 results - conference call press [2010.2.18] kﾎPresentation Pharming full year 2009 results - conference call analysts[2010.2.18] ●Public Report Summary[2010.5.27] ■Press Releases Pharming’s RuconestmV For HAE Granted European Marketing Authorization[2010.10.28]
Pharming And Swedish Orphan Announce Publication Of Randomized Clinical Trial Results With Pharming’s Recombinant Human C1 Inhibitor[2010.10.5]
Pharming Signs Commercialization Agreement With Santarus For Rhucin@� In North America[2010.9.13]
Pharming Plans Submission Rhucin BLA To Us FDA End 2010[2010.8.25]
Pharming And Sanofi Chimie Sign Manufacturing Agreement For The Drug Substance Of RuconestmV[2010.7.6]
Pharming Receives Positive Opinion From European Medicines Agency On Rhucin[2010.6.24]
Pharming Submits D180 Response For Rhucin MAA To EMA Without Clock Stop[2010.5.25]
Pharming Receives D180 List Of Outstanding Issues On Rhucin MAA[2010.5.21]
Swedish Orphan Biovitrum And Pharming Sign Rhucin@� Distribution Agreement[2010.4.15]
Pharming’s C1 Inhibitor Effective In Preventing AMR In Animal Model Of Transplant Rejection[2010.4.1]
Pharming Submits Response To Questions MAA Rhucin[2010.3.18]
Pharming’s C1 Inhibitor Product Potentially Effective In Reducing Complications Following Transplantation[2010.2.17]
Pharming Gives Update On Rhucin EU Marketing Authorization Application[2010.1.22]
Pharming Confirms Interaction With US FDA For Rhucin[2009.12.9]
Pharming Recombinant Human C1 Inhibitor: Results In Pre-clinical Ischaemic Reperfusion Model Confirm Potential For New Indications[2009.10.22]
Pharming’s Marketing Authorisation Application For Rhucin Validated By The European Medicines Agency (EMEA)[2009.9.23]
Pharming Submits Marketing Authorisation Application For Rhucin@� To The EMEA[2009.9.3]
Pharming Confirms Positive Results From Final Analysis Of Rhucin@� Studies[2009.7.1]
■Pharmion Corporation[米]
- http://www.pharmion.com/ Celgene Completes $2.9 Billion Acquisition of Pharmion[2008.3.7] - 2007.11.18 合併契約。 ●決算●個別製品売上高
($ milllion) 2007 2006 2005 2004 2003 2002 2001 2000 売上高 267,300 238,646 221,244 130,171 25,539 4,735 - - 営業利益 (69,248) (90,164) 4,589 (12,099) (48,620) (35,701) (14,331) (4,636) 純利益 (63,860) (91,012) 2,269 (17,537) (50,059) (34,697) (13,710) (4,446) 研究開発費 102,369 70,145 42,944 28,392 24,616 15,049 6,009 972 取得研究開発費 8,000 78,763 21,243 - - 従業員数 513 ★Thalidomide[thalidomide] 多発性骨髄腫 北米・アジア以外の全世界 [2007] 欧州では多発性骨髄腫や他の癌にon a compassionate use or named patient basisで 広範囲に使用。 承認地域はAustralia, New Zealand, Turkey, Israel, South Korea, South Africa and Thailand for the treatment of multiple myeloma after the failure of standard therapies. 2008.1.24 EMEAで承認勧告。 for use in combination with melphalan and prednisone as first line treatment for patients with untreated multiple myeloma, aged 65 years or older or ineligible for high dose chemotherapy ・2001.11 Celgene Corporation (Celgene) から北米・特定アジア以外の全世界ライセンス契約 [競合2007] ・EMEAは既にVelcade[Millenium], Revlimid[Celgene]を承認。両剤とも relapsed and refractory multiple myeloma で承認されている。 ・melphalan and dexamethasoneのような旧来療法との競合もある。 ★Vidaza[azacitidine] 骨髄異形成症候群(MDS)治療薬;発売2004.7.1 全世界 [2007] 販売地域U.S., Switzerland, Israel, the Philippines, Hong Kong, Thailand, Turkey, Argentina, South Korea and Lebanon ・2007.1 FDAに静注剤の追加申請 ・2008.1 EMEAに申請 [競合2007] ・Dacogen[MGI Pharma]が承認2006.5、Revlimid[Celgene]が承認2005.12 ・RevlimidはEMEA承認勧告2008.1
($ 000) 2007 2006 2005 2004 2003 備考 Thalidomide 81,681(+5.4) 77,530(-2.3) 79,365 65,300 15,600 [thalidomide] 多発性骨髄腫 Vidaza 165,347(+16.3) 142,219(+13.2) 125,634 47,100 - [azacitidine] 骨髄異形成症候群(MDS)治療薬;発売2004.7.1 その他 20,272(+7.3) 18,897(+16.3) 16,245 売上高 267,300 238,646 221,244 130,171 25,539 4,735 - -
●Pharmion Corporation ●Products http://www.vidaza.com/ Vidaza -Full Prescribing Information[pdf]
●Investors Relations ★SEC Filings 10-K Annual Report[2008.2.29] 10-K Annual Report[03/15/2007] - [pdf] - [xls] 10-K Annual Report[03/16/2006] - [pdf] - [xls] 10-K Annual Report[03/16/2005] - [pdf] - [xls] 10-K Annual Report[03/26/2004] ●Media Center ★News Releases Pharmion Corporation Announces 2005 Financial Results[2006.2.22] Pharmion Announces Q4 Sales of $51.5 Million; 2004 Sales of $130.2 Million[2005.2.14]
商品名 適応 段階 導入先 対象国 競合品 VIDAZA[TM] Myelodysplastic Syndromes Marketed Pharmacia (now part of Pfizer) US Thalomid(R) and Revlimid(TM), each from Celgene, and Decitabine, from Supergen Inc Thalidomide Pharmion Multiple myeloma ENL Marketed Celgene Australia,New Zealand, Turkey, and Israel VelcadeTM, from Millenium Pharmaceuticals Inc., and RevlimidTM, from Celgene Corporation Innohep[R] Treatment of DVT with or without PE Marketed LEO Pharma A/S US LovenoxR, from Aventis, and FragminR, from Pharmacia Corporation; and Refludan(R) Heparin-induced thrombocytopenia Marketed Schering AG Europe/ROW Argatroban, from GlaxoSmithKline plc
■Photocure ASA[NO]
- http://www.photocure.com/ - Oslo Stock Exchange (PHO)上場. photodynamic technology, targeting key dermatology and oncology markets. 1993 創業 1997 従業員雇用開始 Metvix臨床研究開始 2000 Metvixが初の販売承認申請 2001 Metvix初承認。 MetvixをGaldermaにライセンス 2002 Hexvixが初の販売承認申請 2003 Galderma's first Metvix launch 2004 Hexvix初承認 2005 Hexvixが全EU/EEA諸国で承認、Nordic地域で発売、米国申請 2006 HexvixをGE Healthcareヘライセンス。 HexvixがEU発売 ●会社決算
(NOK 000) 2006 2005 2004 2003 2002 2001 備考 売上収入 61,667 38,007 36,855 23,380 10,892 Milestone収入 148,653 15,634 40,954 31,774 14,331 総収入 210,320 53,641 77,809 55,154 25,223 売上原価 22,251 13,430 13,066 9,514 5,832 粗利益 188,070 40,211 64,743 45,640 19,391 営業利益 78,342 (47,251) (40,861) (53,655) (109,526) 経常利益 84,730 (-38,474) (45,322) 当期純利益 85,082 (38,210) (45,032) 研究開発費 38,200 38,238 31,718 38,377 77,300 従業員数[連結] 製品売上高/product split Metvix/Aktilite 51,554 36,396 [] Hexvix 10,113 1,411 [] その他 - 200 [] 合計 61,667 38,007 []
●Photocure ASA[NO] ●Products ★Metvix(methyl aminolevulinate) actinic keratosis(AK) /non-melanoma skin cancer (superficial and nodular basal cell carcinoma(BCC) - MetvixR photodynamic therapy (MAL-PDT) ★Hexvix(hexaminolevulinate) 膀胱癌診断 ●R&D ●Investors ★Annual Report 2006[pdf,29p;2007.4.16] ●Press/Media - Press Release Photocure - Metvixia(TM) NDA submitted to FDA[2007.6.28] Approval for Hexvix obtained in Italy[2007.6.19] Price approval and reimbursement for Hexvix obtained in France [2007.5.30] Forth quarter report 2006[2007.2.28] US option for Hexvix exercised by GE Healthcare[2006.7.31] PhotoCure - GE Healthcare has 60 days to exercise US option for Hexvix(R)[2006.5.31] FDA requests more information related to Hexvix(R) NDA[2006.4.20] PhotoCure and GE Healthcare introduce Hexvix in Europe[2006.4.7] Metvix(R) approved for Bowen's in 22 European countries[2005.11.25] Hexvix(R) NDA submitted to FDA[2005.6.30] PhotoCure and Galderma free to market Metvix(R) in Australia[2005.4.6] Hexvix(R) approved in 26 European countries [2005.3.2] - EU/EEA26ヵ国相互承認2005.3.2 2004.12.03★FDA Review of Metvix(R) for the treatment of skin cancer
2004.12.01★Hexvix(R) marketing application found fileable in 26 European countries - EU/EEA26ヵ国に相互承認申請2004.12.1
2004.11.29★Metvix(R) approved in 8 new European countries
2004.09.23★Hexvix(R) application in EU / EEA countries to be filed later this year
2004.09.20★Marketing approval for Hexvix(R) - スエーデン承認2004.9.20
2004.07.28★Regulatory Approval of Metvix(R) in the US
2004.06.17★US New Drug Application approval expected for Metvix
2004.05.27★Galderma initiates new Metvix(R) launches
2003.11.25★Metvix(R) progresses
2003.09.25★Hexvix(R) imaging one step closer to commercialisation
2003.09.11★FDA Advisory Committee Reviews Metvix(R) for the treatment of skin cancer
2003.08.08★Progress in FDA's evaluation of Metvix(R) application
2003.06.17★New approval for Metvix(R) in Australia
2003.05.09★Galderma initiates Metvix(R) PDT UK launch activities
2003.04.02★Positive Metvix(R) PDT results
2003.04.02★Metvix(R) PDT approved in Australia
2003.03.28★Hexvix(R) improves treatment of bladder cancer patients
2003.02.24★Marketing Application for Metvix(R) PDT in Australia Recommended for Approval
2003.02.18★New NDA for Metvix(R) PDT Submitted to FDA
2003.02.06★Metvix(R) PDT Launched in Germany
2002.12.18★PhotoCure Files First MAA for Hexvix(R) Cystoscopy - スエーデン申請2002.12.18
2002.09.23★Metvix(R) PDT approvable in the US
2002.09.03★Positive Phase III Clinical Results for Hexvix(R)
2002.08.19★High Clinical Acceptance of Metvix(R)PDT
2002.05.23★National Marketing Authorisation for Metvix(R) PDT issued in Finland
2002.05.07★Commercialisation of Metvix(R)PDT in Europe on track
2002.03.06★National Marketing Authorisation for Metvix(R) PDT issued in Germany
2002.02.12★Long-term Phase III Study with Metvix(R) for BCC
2002.02.08★PhotoCure Receives Marketing Approval for Metvix(R) PDT in New Zealand
2002.02.01★Metvix(R) PDT approved in Norway
2002.01.15★Metvix(R) application Switzerland
■Laboratoires Pirre Fabre[FR]
- http://www.pierre-fabre.com/ 民間の医薬品メーカーとしてフランスで第２位 、薬局におけるデルモコスメティック （皮膚科学化粧品）の分野の企業としてヨーロッパで第１位 。ホメオパシー分野世界２位。 1951年 薬剤師ピエール ファーブル、カストルに薬局を開設。 1960年 トゥールーズ大学との共同研究で、西洋ヒイラギ「ラスカス」から静脈不全薬≪ＣＹＣＬＯ３≫を開発。 1961年 ピエール ファーブル社設立。 1963年 歯科医療メーカー、イナバ・ラボラトリーズを買収。Inava Labs 1965年 化粧品部開設。化粧品会社クロラーヌ・ラボラトリーズを買収。Klorane Labs 1968年 カストルにペロデル研究所を開設。 1969年 化粧品会社デュクレ・ラボラトリーズを買収。 Ducray Labs 1970～73年 スペイン、ドイツ、イタリアに子会社を設立。 1975年 アベンヌ村のアベンヌ源泉の水利権購入、並びに再開発に着手。 1977～78年 アメリカとベネリュクス諸国（オランダ、ベルギー、ルクセンブルグ）に子会社を設立。 1980年 資生堂と合弁で、パリにシセイドウ フランスを設立。 1986年 資生堂と合弁で、東京に（株）ピエール ファーブル ジャポンを設立。 1987年 トゥールーズに皮膚科学・化粧品研究所を開設。 1988年 ＩＢＭと分子模型製作について技術提携を行なう。 1989年 非小細胞性肺癌薬「ナベルビン」を発売。 アベンヌ村に化粧品生産工場を建設。Avene Labs スイスの製薬会社ロバファルム・ラボラトリーズを買収。 1990年 アメリカのフィジシャン・フォーミュラ・コスメチック社を買収。 アベンヌ村に新アベンヌ テルマリズムセンターとホテルを開設。 サンジュリアンに免疫学・バイオテクノロジー研究所を開設。 1991年 ヨーロッパ及びアメリカの薬事法規制に合致したアキテーヌ・ファーム・インターナショナル工場開設。 （南仏ポー／注射薬・抗有糸分裂薬を生産） 1992年 ガイヤックに植物抽出工場を開設。 1993年 ローヌ・プーラン・ローラー社のロワールジアン工場を買収。 1994年 トゥールーズ（ビグレ）の皮膚科学・化粧品研究所を拡大。 89年に発売した抗癌剤「ナベルビン」は、アメリカＦＤＡの認可を受ける。 1997年 ピエール ファーブル社の医薬品部門と化粧品部門がそれぞれ独立し、株式会社となる。 1998年 ホメオパシー（同毒療法）大手のドリゾス社を買収 Dolisos 1999年 協和発酵と提携し、抗癌剤「ナベルビン」を医療用薬品として日本市場へ導入。 旭化成と提携し、抗うつ剤「ドレドミン」を医療用薬品として日本市場へ導入。 2002年 パリで開催された世界皮膚科学会において、ピエール ファーブル社のシンポ ジウムを開催し、アベンヌ温泉水及び、レアルバオート麦の安全性と有効性 について皮膚科医や研究者が発表。 アメリカのＭＲ活動ネットワーク会社、ジェネシスを買収。 from 仏ピエール ファーブル社の歩み従業員数(2006)内訳Pierre Fabre Medicament 4,578;Pierre Fabre Dermo-Cosmetique 3,593 ; Pierre Fabre Sante 752
(Eur milllion) 2006 2005 2004 2003 2002 2001 売上高 1,580 1,486 1,470 1,426 1,335 1,250 Family Medication 299[19%] 110[8%] Dermo-Cosmetics 719[45%] 607[42%] Pharmacy 548[35%] 705[50%] 営業利益 68.3 102.8 104.6 当期純利益 37.8 64.3 81.7 研究開発費 182.2 165.2 115[20%] 従業員数[連結] 8,923 8,620 9,300 9,000 ●提携 Commercial partnerships : ・In the United Kingdom, Boots market some of Pierre Fabre Dermo-Cosmetique's ranges ・NAVELBINE R marketed in the United States by GlaxoSmithKline and in Japan by KYOWA-HAKKO ・Nicopatch R , Fluvastatine (FRACTAL R) , Benazepril (BRIEM R, BRIAZIDE R) : Licence and co-Marketing with Novartis ・Lercanidipine (LERCAN R) : Licence and co-Marketing with Recordati ・Raloxifene (OPTRUMA R) : Co-marketing with Eli Lilly ・Milnacipran (IXEL(R)) marketed in Japan by ASAHI ●製品 /2008.3.13from 2005 annual report[pdf,31p] p13 ●開発中の新薬 /2008.3.13
Brands* 成分 Indications 備考 ●Retail Pharmacy Market PERMIXON 植物エキスSerenoa repens Prostate /BPH LERCAN Lercanidipine Anti-hypertension Recordati導入品 FRACTAL fluvastatin Cholesterol-lowering agent Novartis導入品 CYCLO 3 Ruscus. aculeatus extract, hesperidin methylchalcone and ascorbic acid Veinotonic微小循環改善剤 BREXIN piroxicam beta-CD Anti-inflammatory OPTRUMA raloxifene Osteoporosis Lilly導入品 TARDYFERON oral ferrous sulfate Iron deficiency TANGANIL acetyl-dl-leucine(acetylleucine) Anti-vertigo IXEL milnacipran Anti-depressant トレドミン錠[旭化成ファーマ] DIAFUSOR nitroglycerin Anti-angina nitrous transdermal ISKEDYL Dihydroergocristine mesilate; raubasine Cerebral vasodilator ●Hospital Market NAVELBINE vinorelbine Cancer(lung and breast) ナベルビン注[協和発酵] Busilvex paediatric busulfan (pre-packaged for bone marrow transplant) 加ESP PHARMA共同開発
ブスルフェクス点滴静注用60mg[キリン]from 2005 annual report[pdf,31p] p13 を更新
段階 治験薬 適応 備考 ●Oncology 前臨床 F14512 topoisomerase II inhibitor(solid tumours)標的療法薬 P1 Oral Javlor(TM)(vinflunine) (solid tumours) 北米・日本含むアジアBMSに導出 F50035 /MK 0646 (anticorps anti IGF1R) Merck開発 F60008[PG490-88] (omtriptolide sodium) apoptosis inducer(haematological and AML) 米PHARMAGENESIS共同開発 P2 Eniluracil/ADH-300004 5FU Enhancer(liver cancer) 米Adherex開発 P3 ★Inj. Javlor(vinflunine) (NSCLC, 2nd line bladder,breast) 北米・日本含むアジアBMSに導出 申請中 CI-18 /ONECTYL(R) (leuproreln microsphere formulation) Anti-androgen(prostate) Bicalutamide Anti-androgen(prostate) 導入品；カソデックス ●Central Nervous System 前臨床 F14413 (Alzheimer's) F15441 (schizophrenia) F16242 (depression) Donitriptan(F 11356) (migraine) P2 F2695 (anxiety,depression) (active enantiomer of milnacipran) F13640 (chronic pain) Idazoxan(RX 781094) (schizophrenia) 米POTOMAC Pharma共同開発 P3 Milnacipran 追加適応(fibromyalgia) 米FOREST Inc.&CYPRESS BIOSCIENCE共同開発 ●Cardio-vascular 前臨床 F15845 (cardiac ischemia) F 16505 (metabolic syndrome) F 16482 (metabolic syndrome) P1 FELODIPINE patch (arterial hypertension) ギリシャLAVIPHARM 共同開発 ●Internal Medicine & Oncology P3 Permixon (Serenoa repens) 追加適応(prostate hypertrophyl) 承認済 Testopatch(testosterone-in-adhesive matrix patch) (androgenic deficit)
●Laboratoires Pierre Fabre - http://www.pierre-fabre.com/ ; 英文版 ●Communication Area ★Press Release ★Latest News ★Informatoin 2005 annual report[pdf,31p]
●日本 （株）ピエール ファーブル ジャポン - 1986年５月資生堂とピエール ファーブル社の合弁会社として設立。 (ピエール ファーブル社のアベンヌ（化粧品）の輸入販売。)
■Pliva d.d.[Croatia]
- http://www.pliva.com/; www.pliva.hrはクロアチア語頁 1935年創立、本社クロアチア。 33カ国に従業員7000人(2002)。 尚、類似名のPliva Inc.は米国籍の医薬ジェネリック会社で関連はない。 ●決算 ($million) 2004 2003 2002
TOTAL REVENUE 1130.1(+4.9) 1077.7(+32.1) 815.6 粗利益 664.5 659.4 営業利益 166.3 189.2 経常利益 142.4 167.3 純利益 129.3 146.8
研究開発費 115.1 108.0 ●製品売上 ($million) 2004 2003 2002
Pharmaceuticals 736.7(+5.8) 654.4(+47.5) 443.7
Urecholine 12.0(-77) 50.7 bethanechol Sumamed 51(+5) 48.5 azithromycin Sanctura -(発売2004.8) - trospium cl 過活動膀胱 ★事業別売上 ($million) 2004 2003 2002
Pharmaceuticals* 736.7(+5.8) 654.4(+47.5) 443.7 OTC - 41.8(+4.8) 39.8 Pharma Chemicals** 123.6(+10.5) 111.8(-9.7) 123.8 (うちAzithromycin) [99(+17)] [84.3(-16)] [] Non-Core Business*** 53.6(+6.3) 50.4 - DDDI - 20.7(+16.9) 17.7 AH & Agrochemicals - 29.8(+5.3) 28.3 Other 4.2(+14.0) 3.7(+13.4) 3.3 TOTAL SALES 918.1(+6.5) 862.1(+31.3) 656.6 Research(Royalties) 169.8(-6.9) 182.5(+29.9) 140.5(Azithromycin関連) Other income 42.3(+27.6) 33.1(+78.8) 18.5 TOTAL REVENUE 1130.1(+4.9) 1077.7(+32.1) 815.6 Pharmaceuticals* は,RxおよびOTC含む Pharma Chemicals** は,旧 Fine Chemicals Non-Core Business*** は,AH & AgrochemicalsおよびDDDI(Diagnostics,Disinfectants, Dialysis,and infusions)を含む。 ★地域別売上 ($million) 2004 2003 2002 North America 467.3(-0.1) 468.0(+58.6) 295.1 CEE* 442.9(+8.1) 409.7(+12.4) 364.6 *Russia and CIS諸国 Western Europe 206.4(+10.6) 186.6(+31.0) 142.5 ROW 13.5(+0.2) 13.5(+0.3) 13.4 TOTAL 1130.1(+4.9) 1077.7(+32.1) 815.6
●Pliva d.d ●Products SUMAMED(R) (capsules 6*250 mg) Azithromycin [product details] SUMAMED(R) (injections 5* 500 mg) Azithromycin [product details] SUMAMED(R) (syrup 20 ml100mg/5ml) Azithromycin [product details] SUMAMED(R) (tablets 2*500 mg) Azithromycin [product details] SUMAMED(R) (tablets 3*500 mg) Azithromycin [product details] SUMAMED(R) (tablets 6*125 mg) Azithromycin [product details] SUMAMED(R) FORTE (syrup 20 ml 200mg/5ml) Azithromycin [product details] SUMAMED(R) FORTE (syrup 30 ml 200mg/5ml) Azithromycin [product details] ●R&D ★Pipeline ●Investor's ★Financial Reports Annual Report 2004[2005.4.28,pdf,97p] PLIVA Announces FY 2004 Results[pdf,11p;2005.3.2] PLIVA Announces Full Year 2003 Results[,pdf,14p] ●Press Center Odyssey Pharmaceuticals,Inc.[Pliva米国子会社]
●Odyssey Pharmaceuticals,Inc. - http://www.odysseypharm.com/ PLIVA d.d.'s specialty branded subsidiary ●Products Sanctura - Prescribing Information[pdf,15p] - Prescribing Information[pdf] - FDA Approval Letter[pdf] - http://www.sanctura.com/ ●News Sanctura FDA Approved for Overactive Bladder[5/31/2004]
■POZEN Inc[US]
- http://www.pozen.com/default.asp ; 従業員38人; 米North Carolina 創立 1996 IPO 2000.10 NASDAQ:POZEN ●会社決算
($ 000) 2009 2008 2007 2006 2005 2004 2003 2002 2001 総収入 28,647 13,517 53,444 13,517 28,647 23,088 3,717 (ライセンス収入) 28,419 8,682 34,459 8,682 28,419 22,562 3,717 (開発収入) 228 4,835 18,985 4,835 228 526 - 営業利益 経常利益 1,959 (19,310) 5,333 (19,310) 1,959 (5,261) (14,863) 当期純利益 1,959 (19,310) 4,666 (19,310) 1,959 (5,261) (14,863) 研究開発費 18,769 22,359 39.963 22.359 18.769 20.399 9.904 従業員数[連結] 31 38
●Treximet(TM)(旧名Trexima) 片頭痛薬 【2009】
We have developed Treximet@� in collaboration with GlaxoSmithKline, or GSK. Treximet is the brand name for the product combining sumatriptan 85 mg, formulated with RT TechnologymV and naproxen sodium 500 mg in a single tablet designed for the acute treatment of migraine. On April 15, 2008, the U.S. Food and Drug Administration, or FDA, approved Treximet for the acute treatment of migraine attacks with or without aura in adults. Upon receipt of FDA approval, GSK notified us of its intention to launch the product and Treximet was available in pharmacies in May 2008.Treximet incorporates our MT 400 technology, which refers to our proprietary combinations of a triptan (5-HT1B/1D agonist) and a non-steroidal anti-inflammatory drug, or NSAID. Under our MT 400 technology, we sought to develop product candidates that provide acute migraine therapy by combining the activity of two drugs that act by different mechanisms to reduce the pain and associated symptoms of migraine. We filed the new drug application, or NDA, for Treximet with the FDA in August 2005, and in June 2006 we received an approvable letter requiring us to provide certain additional safety information relating to Treximet, some of which required new studies. An approvable letter is an official notification from the FDA that contains conditions that must be satisfied prior to obtaining final U.S. marketing approval. In early January 2007, we delivered a full response to this approvable letter that provided additional data and analyses and supporting information addressing the FDA’s safety concerns, including cardiovascular safety. On August 1, 2007, we received a second approvable letter from the FDA for Treximet in which the FDA requested that we further address the FDA’s concern about the product’s potential for genotoxicity. In response to this approvable letter, we submitted the results of three non-clinical (in vitro) studies that provided clarifying information about the Chinese Hamster Ovary, or CHO, assay and data from a clinical evaluation of the genotoxic potential of Treximet in human volunteers which indicated that no chromosomal aberrations were induced in peripheral blood lymphocytes when Treximet was administered to volunteers for seven days. On April 15, 2008, the FDA approved Treximet for the acute treatment of migraine attacks with or without aura in adults.
【2007】
We have developed Treximet(TM) in collaboration with GlaxoSmithKline, or GSK. Treximet is the proposed brand name for the product candidate combining sumatriptan 85 mg, as the succinate salt, formulated with RT Technology(TM) and naproxen sodium 500 mg in a single tablet designed for the acute treatment of migraine. The FDA has notified us that it has tentatively accepted the trade name Treximet(TM), subject to final approval of the NDA for the product.Treximet incorporates our MT 400 technology, which refers to our proprietary combinations of a triptan (5-HT1B/1D agonist) and a non-steroidal anti-inflammatory drug, or NSAID. Under our MT 400 technology, we sought to develop product candidates that provide acute migraine therapy by combining the activity of two drugs that act by different mechanisms to reduce the pain and associated symptoms of migraine. We filed the NDA for Treximet with the FDA in August 2005 and in June 2006, we received an approvable letter requiring us to provide certain additional safety information relating to Treximet, some of which required new studies. An approvable letter is an official notification from the FDA that contains conditions that must be satisfied prior to obtaining final U.S. marketing approval. We, along with GSK, met with the FDA in July 2006 to discuss the approvable letter and we submitted a response to the FDA’s approvable letter in November 2006. In December 2006, the FDA told us that our response was not a complete submission and requested that we provide additional analyses and supporting information relating to the data we submitted in our November 2006 response. The FDA also indicated that it was necessary to provide a complete and accurate presentation of these data which had to sufficiently address their safety concerns, including cardiovascular safety. We worked with GSK to compile and format the additional data requested by the FDA and delivered a revised full response to the FDA in early February 2007. On August 1, 2007, we received a second approvable letter from the FDA for Treximet. In that letter, the FDA requested that POZEN further address the FDA’s concern about the product’s potential for genotoxicity. Together with GSK, we met with the FDA in September 2007 and filed a response to the second approvable letter in October 2007. The submission included, in addition to a required routine Safety Update and updated product labeling, the results of three non-clinical (in vitro) studies that provided clarifying information about the Chinese Hamster Ovary, or CHO, assay. The FDA notified us that it considered the response to be a complete, Class II response (six month review) which could result in a new decision date of April 15, 2008. In addition, we conducted a clinical evaluation of the genotoxic potential of Treximet in human volunteers. The results from this study, which were submitted to the FDA on January 14, 2008, indicated that no chromosomal aberrations were induced in peripheral blood lymphocytes when Treximet was administered to volunteers for seven days. We believe that the submission of this additional data will not result in any change to the April 15, 2008 decision date; however, the FDA could decide to extend the date in order to have additional time to review this data.
MT 400/Treximet
In June 2006, we received an approvable letter from the FDA related to the NDA for Treximet. An approvable letter is an official notification from the FDA that contains conditions that must be satisfied prior to obtaining final U.S. marketing approval. The approvable letter reflected that the FDA has determined that Treximet is effective as an acute treatment for migraine headaches. The FDA requested additional safety information on Treximet, some of which required new studies. After meeting with the FDA in July 2006, we and GSK submitted a response to the approvable letter in November 2006 using additional data from GSK sponsored clinical trials. In December 2006, we received notification that the response was not yet considered complete. Specifically, the FDA requested that we provide additional analyses and supporting information relating to the data we submitted in our November 2006 response. The FDA also indicated that it was necessary to provide a complete and accurate presentation of these data which had to sufficiently address their safety concerns, including cardiovascular safety. We worked with GSK to compile and format the additional data requested by the FDA and delivered a revised full response to the FDA in early February 2007. On August 1, 2007, we received a second approvable letter from the FDA for Treximet. In that letter, the FDA requested that we further address the FDA’s concern about the product’s potential for genotoxicity. Together with GSK, we met with the FDA in September 2007 and submitted a response in October 2007 to the second approvable letter. The submission included, in addition to a required routine Safety Update and updated product labeling, the results of three non-clinical (in vitro) studies that provided clarifying information about the CHO assay. The FDA notified us that it considered the response to be a complete, Class II response (six month review) which could result in a new decision date of April 15, 2008.
In addition, we conducted a clinical evaluation of the genotoxic potential of Treximet in human volunteers in the event the FDA required this information. The results from this study, which were submitted to the FDA on January 14, 2008, indicated that no chromosomal aberrations were induced in peripheral blood lymphocytes when Treximet was administered to volunteers for seven days. We believe that the submission of this additional data will not result in any change to the April 15, 2008 decision date; however, the FDA could decide to extend the date in order to have additional time to review this data.
As part of our NDA program for Treximet, we conducted five Phase 1 trials, two Phase 3 pivotal trials, and one 12-month open label safety trial using a formulation of Treximet developed by GSK. The Phase 3 pivotal trials, including the endpoints required to evaluate Treximet, were designed to demonstrate superiority to placebo for relief of pain and the associated symptoms of migraine (nausea, photophobia and phonophobia) at two hours. Additionally, the program was designed to demonstrate that each component makes a contribution to the efficacy of Treximet (the “combination drug rule” that the FDA requires of all combination products). The efficacy endpoint for the combination was sustained pain free, which is defined as improvement from moderate or severe pain to no pain at two hours and remaining at no pain through twenty four hours without the use of rescue medicine. Further, GSK continues to conduct pre-approval market support studies for Treximet under our IND.
We cannot reasonably estimate or know the amount or timing of the costs necessary to obtain regulatory approval of Treximet. In the second approvable letter from FDA for Treximet which we received on August 1, 2007, the FDA requested that POZEN further address its concern about the potential implications from one preclinical in vitro chromosomal aberration study, and one of four standard genotoxicity assays, in which a signal for genotoxicity was seen for the combination of naproxen sodium and sumatriptan. Together with GSK, we met with the FDA to discuss the proposed plan for addressing their concerns and we filed a response to the approvable letter in October which contained new non-clinical information. We also conducted and submitted the results from a short-term clinical study of the genotoxic potential of Treximet in human volunteers. However, it is unknown whether the non-clinical and clinical data submitted will adequately address the FDA’s concerns and there are no guarantees that the FDA will find our response to the second approvable letter to be sufficient, that testing in addition to the short-term clinical study we performed will not be needed to address the FDA’s concerns described in the second approvable letter or to address other issues the FDA may raise in the future, that additional warnings will not be required on the product labeling, or that the FDA will approve the NDA. In the event that additional clinical trials or other research and development activities are required, under our agreement, GSK will be responsible for the costs of such additional trials or activities, except for our personnel-related costs. Further, we have no assurance that GSK will continue with the development of the product in the event of additional delays in obtaining marketing approval.
We incurred $0.9 million in direct development costs associated with the development of MT400/Treximet for the year ended December 31, 2007 and have incurred $25.5 million in costs from inception to date. We billed GSK $1.1 million for Treximet activities for the year ended December 31, 2007 and billed $1.9 million from inception to date. Our direct development costs do not include the cost of research and development personnel or any allocation of our overhead expenses.
GlaxoSmithKline (GSK)
In June 2003, we signed an agreement with GSK for the development and commercialization of proprietary combinations of a triptan (5-HT1B/1D agonist) and a long-acting NSAID. The combinations covered by the agreement are among the combinations of MT 400. Under the terms of the agreement, GSK has exclusive rights in the U.S. to commercialize all combinations which combine GSK’s triptans, including Imitrex(R) (sumatriptan succinate) or Amerge(R) (naratriptan hydrochloride), with a long-acting NSAID. We were responsible for development of the first combination product, while GSK provided formulation development and manufacturing. GSK had proposed Trexima as the brand name of the combination of sumatriptan succinate, formulated with GSK’s RT TechnologyTM, and naproxen sodium in a single tablet, but this brand name was not acceptable to the FDA. The FDA has notified us that it has tentatively accepted the trade name Treximet, subject to final approval of the NDA for the product. Pursuant to the terms of the agreement, we received $25.0 million in initial payments from GSK following termination of the waiting period under the Hart-Scott-Rodino notification program and the issuance of a specified patent. In May 2004, we received a $15.0 million milestone payment as a result of our commencement of Phase 3 clinical trial activities. In October 2005, we received a $20.0 million milestone payment upon the FDA’s acceptance for review of the Treximet NDA. Additionally, GSK is obligated to make payments to us in a total amount of $20.0 million upon FDA approval of the Treximet NDA and GSK’s notification of intent to commercialize Treximet. In addition, GSK will pay us two sales performance milestones totaling $80.0 million if certain sales thresholds are achieved. Up to an additional $10.0 million per product is payable upon achievement of milestones relating to other products. GSK will also pay us royalties on all net sales of marketed products until at least the expiration of the last to expire issued applicable patent (August 14, 2017) based upon the scheduled expiration of currently issued patents). GSK may reduce, but not eliminate, the royalty payable to us if generic competitors attain a pre-determined share of the market for the combination product, or if GSK owes a royalty to one or more third parties for rights it licenses from such third parties to commercialize the product. The agreement terminates on the date of expiration of all royalty obligations unless earlier terminated by either party for a material breach or by GSK at any time upon ninety (90) days’ written notice to us for any reason or no reason. Among the contract breaches that would entitle us to terminate the agreement is GSK’s determination not to further develop or to launch the combination product under certain circumstances. GSK has the right, but not the obligation, to bring, at its own expense, an action for infringement of certain patents by third parties. If GSK does not bring any such action within a certain time frame, we have the right, at our own expense, to bring the appropriate action. With regard to certain other patent infringements, we have the sole right to bring an action against the infringing third party. Each party generally has the duty to indemnify the other for damages arising from breaches of each party’s representations, warranties and obligations under the agreement, as well as for gross negligence or intentional misconduct. We also have a duty to indemnify GSK for damages arising from our development and manufacture of MT 400 prior to the effective date of the agreement, and each party must indemnify the other for damages arising from the development and manufacture of any combination product after the effective date.
【2007 片頭痛薬市場】
Migraine is characterized by recurring attacks of headache, often associated with visual, auditory or gastrointestinal disturbances. While the precise mechanism of migraine is unknown, researchers believe migraine attacks are caused by acute inflammation surrounding selected blood vessels in the head. The average migraine sufferer experiences the first attack during the early teen years, and the attacks generally continue throughout adulthood.Not all migraine attacks are of the same severity. Consequently, various types of oral, intranasal and injectable therapies are used to treat different types of migraine attacks. Many patients use a personal, individually developed, step-care approach to treat their attacks. Attacks are often treated initially with simple over-the-counter analgesics, particularly if the patient is unable to determine if the attack is a migraine or some other type of headache. If over-the-counter remedies are unsuccessful, patients often turn to more potent prescription drugs, including triptans, narcotics, and analgesic/narcotic drug combinations.
Triptans are the family of drugs most commonly prescribed for the treatment of migraine attacks. Triptans have demonstrated the ability to treat migraines by constricting blood vessels in the brain. Although triptans can be effective in treating migraine symptoms, they are often associated with significant side effects and other disadvantages that include:
・ the occurrence of cardiovascular related events, including chest pain/discomfort, throat discomfort and warm/cold sensations;
・ the potential for other serious cardiovascular events, including death;
・ difficulty in producing sustained benefits with a single dose in a majority of patients;
・ the occurrence of nausea and dizziness during treatment; and
・ the need for cardiovascular evaluations from physicians before initially prescribing triptans to patients with cardiovascular disease risk factors.Despite these shortcomings, according to IMS Health’s IMS National Sales PerspectiveTM, or IMS, in 2007 total triptan sales in the U.S. were approximately $2.3 billion. ImitrexR, marketed by GSK, is the leading triptan product. There are currently three types of Imitrex formulations commercially available: oral, intranasal and injectable. According to IMS, U.S. sales for Imitrex of all three of these formulations totaled approximately $1.3 billion in 2007. An oral triptan is often the physician’s first choice as a prescription treatment for migraine pain. Intranasal triptans are often prescribed for patients requiring faster relief than oral drugs can provide or who cannot take oral medications. For the most severe attacks, patients sometimes use an injectable form of a triptan.
●MT100 (metoclopramide HCl + naproxen sodium) 片頭痛 【2007】 ●MT 300 (dihydroergotamine mesylate("DHE")充填済み注射用シリンジ) 片頭痛 【2007】NDA申請取下げ予定。 ●VIMOVO(naproxen and esomeprazole magnesium) 【2009】
Under our PN program, we have completed formulation development and clinical studies for several combinations of a PPI and a NSAID in a single tablet intended to provide effective management of pain and inflammation associated with chronic conditions such as osteoarthritis, and intended to have fewer gastrointestinal complications compared to a NSAID taken alone in patients at risk for developing NSAID associated gastric ulcers. We initially conducted studies with two PN product formulations in this program - PN 100, a combination of the PPI lansoprazole and the NSAID naproxen, and PN 200, a combination of the PPI omeprazole and naproxen, prior to entering into our collaboration with AstraZeneca. Our present development and commercialization efforts under the PN program are covered under our exclusive collaboration agreement with AstraZeneca, which we entered into on August 1, 2006 and which was amended in September 2007 and October 2008. Under our agreement with AstraZeneca, we are co-developing with AstraZeneca, and AstraZeneca will commercialize, proprietary fixed dose combinations of the PPI esomeprazole magnesium with the NSAID naproxen in a single tablet. The initial product to be developed under the agreement, VIMOVO® (formerly PN 400), is being studied for the treatment of the signs and symptoms of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis in patients at risk of developing NSAID-associated gastric ulcers. On March 2, 2007, we filed an IND with the FDA for VIMOVO and in April 2007, the first Phase 1 study was initiated.In discussions with the FDA during 2005 regarding our development plans for studies to pursue FDA approval of PN 100 and PN 200, the FDA agreed that by including naproxen as the NSAID within the PN formulation, we could expect that all indications for chronic use of naproxen in adults would accrue to the PN product, if clinical trials successfully demonstrated improved safety (lower incidence of gastric ulcers) of the PN product compared with naproxen alone and the PN formulation was shown to be bioequivalent to marketed formulations of enteric-coated, or EC, naproxen. Prior to entering into our collaboration agreement with AstraZeneca, we completed a study designed to demonstrate the bioequivalence of the naproxen component of our PN 200 product candidate development formulation to EC naproxen. This study demonstrated that the PN 200 product was bioequivalent to the reference drug, EC Naprosyn®, with respect to the naproxen component.
In early 2006, we submitted a Special Protocol Assessment, or SPA, to the FDA for our pivotal Phase 3 clinical trials for PN 200. The SPA is a process in which the FDA provides evaluations and guidance on clinical trial protocols for pivotal Phase 3 clinical trials. In April 2006, we announced that we had reached an agreement with the FDA on the Phase 3 pivotal clinical trials for PN 200 for the treatment of the signs and symptoms of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis in patients at risk of developing NSAID-associated gastric ulcers. We also reached agreement with the FDA that the development program and study design proposed for PN 200 would be applicable to a product that contained an isomer of omeprazole combined with naproxen. In light of our collaboration agreement with AstraZeneca, we, along with AstraZeneca have met with the FDA and confirmed the core development program and the principles in the SPA already agreed upon do apply to the new product consisting of proprietary fixed dose combinations of esomeprazole magnesium with naproxen.
In the third quarter of 2006, we began recruiting subjects for a six month comparative trial of PN 200 as compared to EC naproxen in patients requiring chronic NSAID therapy. The primary endpoint for the trial was the cumulative incidence of gastric ulcers over six months of treatment. Because we did not have final results until the fourth quarter of 2007, we, together with AstraZeneca reviewed the interim results of this trial prior to commencing Phase 3 studies of VIMOVO in September 2007. This study has now been completed and the results which have been presented publicly, indicated significantly fewer endoscopically confirmed gastric ulcers during the six month treatment period in subjects on PN 200 compared to subjects receiving enteric-coated naproxen alone. We conducted two Phase 3 pivotal trials of VIMOVO in patients who are at risk for developing NSAID-associated gastric ulcers, the primary endpoint for which is the reduction in endoscopic gastric ulcers. In October 2008, the FDA informed us that it was conducting an internal review of the acceptability of using endoscopic gastric ulcers as a primary endpoint in clinical trials. In late January 2009, the FDA informed us that it had completed its internal discussions and that there was no change to previous agreements that gastric ulcer incidence was an acceptable primary endpoint for our clinical programs. The two pivotal trials have been completed and met their primary endpoints. In both trials, patients taking VIMOVO experienced significantly (p<0.001) fewer endoscopically confirmed gastric ulcers compared to subjects receiving enteric-coated naproxen during the six-month treatment period, with gastric ulcer incidence rates of 4.1 and 7.1% for VIMOVO and 23.1 and 24.3% for enteric-coated naproxen in studies 301 and 302, respectively. Data combined from both studies showed that in patients taking low dose aspirin (n=201), the incidence of gastric ulcers in the VIMOVO arm was 3.0% compared to 28.4% for those taking EC naproxen (p<0.001) and patients taking VIMOVO who were not taking low dose aspirin (n=653) experienced a 6.4% incidence of gastric ulcers compared to 22.2% among those taking EC naproxen (p<0.001). Additional analyses examined the incidence of endoscopically confirmed duodenal ulcers among patients taking VIMOVO. In study 301, patients taking VIMOVO experienced a 0.5% incidence of duodenal ulcers compared to 5.1% taking EC naproxen (p=0.003), and in study 302, patients taking VIMOVO experienced a 1.0% incidence of duodenal ulcers, compared to 5.7% incidence among patients taking EC naproxen (p=0.007). The most frequently reported adverse events among patients taking both VIMOVO and enteric coated naproxen in the pivotal trials were GI disorders, including dyspepsia, erosive esophagitis and erosive duodenitis. In addition, we are conducting a long-term, open label safety study for VIMOVO. We have terminated a non-pivotal smaller study in patients at high risk (i.e., previous bleeding from a gastric ulcer) of gastrointestinal related events from NSAIDs which is not required for approval. We have conducted additional studies at AstraZeneca’s expense. The NDA for VIMOVO was submitted on June 30, 2009 and was accepted for filing in August 2009. POZEN received a $10.0 million milestone payment from AstraZeneca in September 2009 for the achievement of such milestone.
In 2005, we also had discussions with the FDA concerning the implications of the FDA’s guidance issued in June 2005 concerning labeling of NSAID-containing products, which resulted from an FDA advisory committee meeting held in February 2005. The advisory committee addressed the safety of NSAIDs, and, in particular, the cardiovascular risks of COX-2 selective NSAIDs. Based on our discussions with the FDA reviewing division for PN products, we believe that, unless new information about naproxen safety concerns becomes available, long-term cardiovascular safety studies will not be required at this time for FDA approval of our PN product candidates containing naproxen. However, we cannot guarantee that such studies will not be required. We will continue to evaluate and review with the FDA its expectations and recommendations regarding the efficacy and safety requirements and study design necessary to support approval of NDAs for our PN product candidates.
Additionally, we have met with four national European regulatory agencies to discuss the proposed development program for PN. Under our agreement with AstraZeneca, AstraZeneca has responsibility for the development program for PN products outside the U.S., including interactions with regulatory agencies. In October 2009, AstraZeneca submitted a MAA for VIMOVO in the European Union via the Decentralized Procedure and plans to file for approval in a number of other countries which are not covered by the Decentralized Procedure.
We cannot reasonably estimate or know the amount or timing of the costs necessary to obtain regulatory approval of VIMOVO. Nor can we reasonably estimate or know the amount or timing of the costs necessary to continue exploratory development and/or complete the development of any PN product candidates we may seek to develop or when, if and to what extent we will receive cash inflows from any PN products. The additional costs that may be incurred include expenses relating to clinical trials and other research and development activities and activities necessary to obtain regulatory approvals.
We incurred direct development costs associated with the development of our PN program of $7.2 million for the fiscal year ended December 31, 2009, of which, $5.5 million was funded by development revenue from AstraZeneca. We incurred total direct development cost of $95.7 million associated with the development of our PN program. Our direct development costs do not include the cost of research and development personnel or any allocation of our overhead expenses.
AstraZeneca AB (AstraZeneca)
In August 2006, we entered into a collaboration and license agreement dated as of August 1, 2006 and effective September 7, 2006 with AstraZeneca, a Swedish corporation, regarding the development and commercialization of proprietary fixed dose combinations of the PPI esomeprazole magnesium with the NSAID naproxen, in a single tablet for the management of pain and inflammation associated with conditions such as osteoarthritis and rheumatoid arthritis in patients who are at risk for developing NSAID associated gastric ulcers. Under the terms of the agreement, we granted to AstraZeneca an exclusive, fee-bearing license, in all countries of the world except Japan, under our patents and know-how relating to combinations of gastroprotective agents and NSAIDs (other than aspirin and its derivatives). AstraZeneca had the right, which has now expired, to elect to include Japan in the licensed territory within two years after the effective date of the agreement. Pursuant to the terms of the agreement, we received an upfront license fee of $40.0 million from AstraZeneca following termination of the waiting period under the Hart-Scott-Rodino notification program.
In September 2007, we agreed with AstraZeneca to amend our collaboration and license agreement effective as of September 6, 2007. Under the terms of the amendment, AstraZeneca has agreed to pay us up to $345.0 million, in the aggregate, in milestone payments upon the achievement of certain development, regulatory and sales events. In September 2007 we received a $10.0 million payment upon execution of the amendment and a $20.0 million payment in recognition of the achievement of the primary endpoints for the PN400-104 study, a study which compared acid suppression of different doses of VIMOVO (formerly PN 400), and achievement of the interim results of the PN200-301 study, a six month comparative trial of PN 200 as compared to EC naproxen in patients requiring chronic NSAID therapy, meeting mutually agreed success criteria. An additional $55.0 million will be paid upon achievement of certain development and regulatory milestones, and $260.0 million will be paid as sales performance milestones if certain aggregate sales thresholds are achieved. Under the original agreement, we were to have received development and regulatory milestones totaling $160.0 million, of which $20.0 million was to be paid upon the successful completion of the proof of concept studies, and sales performance milestones totaling $175.0 million.
In addition, the amendment revised the royalty rates we were to have received under the original agreement. Under the original agreement, we were to receive a royalty based on annual net sales by AstraZeneca, its affiliates or sublicensees during the royalty term. The royalty rate varied based on the level of annual net sales of products made by AstraZeneca, its affiliates and sublicensees, ranging from the mid-single digits to the mid-teens. Under the amendment, we will now receive a flat, low double digit royalty rate during the royalty term on annual net sales of products made by AstraZeneca, its affiliates and sublicensees, in the U.S. and royalties ranging from the mid-single digits to the high-teens on annual net sales of products made by AstraZeneca, its affiliates and sublicensees outside of the U.S. The amendment also revises the rate of reduction to the royalty rate based upon loss of market share due to generic competition inside and outside of the U.S. to account for the new royalty structure.
Our right to receive royalties from AstraZeneca for the sale of such products under the collaboration and license agreement, as amended, expires on a country-by-country basis upon the later of (a) expiration of the last-to-expire of certain patent rights relating to such products in that country, and (b) ten years after the first commercial sale of such products in such country.
We further amended the collaboration and license agreement effective October 1, 2008 to shorten the timing of AstraZeneca’s reimbursement obligation for certain development expenses incurred by us under the agreement and to update the description of the target product profile studies (as defined in the agreement) for VIMOVO.
We retain responsibility for the development and filing of the NDA for the product in the U.S. AstraZeneca is responsible for all development activities outside the U.S., as well as for all manufacturing, marketing, sales and distribution activities worldwide. We have agreed to bear all expenses related to certain specified U.S. development activities. All other development expenses, including all manufacturing-related expenses, will be paid by AstraZeneca. The agreement established joint committees with representation of both us and AstraZeneca to manage the development and commercialization of the product. The committees operate by consensus, but if consensus cannot be reached, we generally will have the deciding vote with respect to development activities required for marketing approval of the product in the U.S. and AstraZeneca generally will have the deciding vote with respect to any other matters.
The agreement, unless earlier terminated, will expire upon the payment of all applicable royalties for the products commercialized under the agreement. Either party has the right to terminate the agreement by notice in writing to the other party upon or after any material breach of the agreement by the other party, if the other party has not cured the breach within 90 days after written notice to cure has been given, with certain exceptions. The parties also can terminate the agreement for cause under certain defined conditions. In addition, AstraZeneca can terminate the agreement, at any time, at will, for any reason or no reason, in its entirety or with respect to countries outside the U.S., upon 90 days’ notice. If terminated at will, AstraZeneca will owe us a specified termination payment or, if termination occurs after the product is launched, AstraZeneca may, at its option, under and subject to the satisfaction of conditions specified in the agreement, elect to transfer the product and all rights to us.
Competition
The competition for our PN products that receive regulatory approval will come from the oral anti-arthritic market, or more specifically the traditional non-selective NSAIDs (such as naproxen and diclofenac), traditional NSAID/gastroprotective agent combination products or combination product packages (such as Arthrotec® and Prevacid® NapraPACTM ) and the only remaining COX-2 inhibitor, Celebrex®. The U.S. prescription market for oral solid NSAIDs was approximately $2.6 billion in 2009, of which 72% was accounted for by Celebrex, according to IMS. This market is continuing to undergo significant change, due to the voluntary withdrawal of Vioxx® by Merck & Co. in September 2004, the FDA-ordered withdrawal of Bextra® by Pfizer in April 2005 and the issuance of a Public Health Advisory by the FDA in April 2005 stating that it would require that manufacturers of all prescription products containing NSAIDs provide warnings regarding the potential for adverse cardiovascular events as well as life-threatening gastrointestinal events associated with the use of NSAIDs. Moreover, subsequent to the FDA advisory committee meeting in February 2005 that addressed the safety of NSAIDs, and, in particular, the cardiovascular risks of COX-2 selective NSAIDs, the FDA has indicated that long-term studies evaluating cardiovascular risk will be required for approval of new NSAID products that may be used on an intermittent or chronic basis. However, based on a meeting with the FDA in September 2005, we believe, although we cannot guarantee, that long-term cardiovascular safety studies may not be required at this time for FDA approval of our PN product candidates containing naproxen.
● 【2009】
●POZEN Inc ●Product Candidates Tremimet(TM)[GSK]片頭痛 発売 PN400(AZN) P3 関節リウマチ PA32540 P2 アスピリン製剤 PA08140 P1 NSAIDS併用 PA32520/50040 P1準備 癌性疼痛 ●Press Releases Reports Second Quarter 2008 Results[2008.7.29] -Treximetの米国新規処方箋比率は片頭痛薬の3.7%(2008.6月) POZEN IND and NDA for Treximet(TM) (Sumatriptan/Naproxen Sodium) Transferred to GlaxoSmithKline[2008.5.14] - 権利をPOZEN →GSKに移行。 Treximet(TM) (Sumatriptan and Naproxen Sodium) Tablets Approved by FDA for Acute Treatment of Migraine[2008.4.15] POZEN Submits Human Lymphocyte Study for Treximet(TM) (Formerly Known as Trexima(TM))[2008.1.15] - 遺伝毒性のボランティアに用いた短期研究結果を本日FDAに提出。 Pozen Announces Trexima(TM) (Sumatriptan Succinate and Naproxen Sodium) Amended Response Accepted for Review by FDA[2007.11.1] POZEN Submits Response to Approvable Letter for Trexima(TM)[2007.10.15] POZEN Plans to Submit Response to Approvable Letter For Trexima(TM) Within the Next Ten Days[2007.10.5] FDA Issues Second Approvable Letter for Trexima (TM)[2007.8.2] Trexima (TM) (Sumatriptan/Naproxen Sodium) Superior Efficacy Data Published in JAMA[2007.4.3] POZEN Announces Trexima(TM) (Sumatriptan Succinate and Naproxen Sodium) Amended Response Accepted for Review by FDA[2007.3.22] Pozen Expects to Submit Revised Response to Trexima(TM) (Sumatriptan/Naproxen Sodium) Approvable Letter by Year End[2006.12.13] POZEN Submits Full Response to FDA Approvable Letter For Trexima(TM)[2006.11.9] New Analysis Shows Patients Who Treat Their Migraine Pain Early With Trexima(TM)
(Sumatriptan Succinate/Naproxen Sodium) Have Higher Sustained Pain-Free Rates Than Those Who Treat Late[2006.9.20] New Data Show Consistent Efficacy and Tolerability of Trexima(TM) (Sumatriptan
Succinate/Naproxen Sodium) Across Multiple Migraine Attacks[2006.9.20] New Data Show Peak Concentration of Sumatriptan Occurred Earlier With Trexima(TM)
(Sumatriptan Succinate/Naproxen Sodium) Compared to ImitrexR (Sumatriptan Succinate)[2006.9.20] September 13, 2006★POZEN To Present at the UBS 2006 Global Life Sciences Conference
July 31, 2006★POZEN to Submit Full Response to Trexima(TM) Approvable Letter During the Fourth Quarter
June 26, 2006★New Data Show Investigational Migraine Therapy Demonstrates Effective Treatment of Migraine-Associated Neck and Sinus Pain
June 26, 2006★New Data Demonstrate Sustained Efficacy of Single Tablet Combination Migraine Therapy Compared to Monotherapy
June 09, 2006★POZEN Inc. and Glaxosmithkline Report Receipt of Approvable Letter for Investigational Migraine Treatment
April 05, 2006★New Data Presented on Satisfaction, Productivity and Long-Term Safety of a Single Tablet Containing Sumatriptan Formulated With RT Technology(TM) and Naproxen Sodium
April 05, 2006★New Pivotal Trial Data Demonstrated Superior Clinical Benefits of Single Tablet Containing Sumatriptan Formulated With RT Technology(TM) and Naproxen Sodium
October 27, 2005★Pozen Reports Third Quarter 2005 Results; Trexima(TM) NDA Accepted for Filing by FDA in October
October 11, 2005★GlaxoSmithKline and POZEN Announce Trexima(TM) (Sumatriptan Succinate and Naproxen Sodium) New Drug Application Accepted for Review by FDA
August 08, 2005★POZEN Submits New Drug Application for Trexima(TM) (Sumatriptan Succinate and Naproxen Sodium) for the Acute Treatment of Migraine
August 05, 2005★POZEN Provides Results of FDA Advisory Committee Meeting on MT 100(TM) (Naproxen Sodium and Metoclopramide Hydrochloride)
July 28, 2005★POZEN Reports Second Quarter 2005 Results; Trexima(TM) NDA on Track for Q3 2005 Submission
April 21, 2005★POZEN Hits All Primary Endpoints in Second Phase III Pivotal Trial for Trexima; NDA Submission Scheduled for 3Q 2005
February 28, 2005★POZEN Reports Fourth Quarter and Year End 2004 Results; Completes First Trexima Phase III Study
January 25, 2005★European Patent Issued to POZEN for Treatment of Migraine
■Investors ●Fact Sheets VIMOVO(TM) Fact Sheet Treximet(TM) Fact Sheet ●Annual and Quarterly Reports 2009 Annual Report 2008 Annual Report 2007 Annual Report ●SEC Filings 10-K Annual Filings[2010.3.9] - [pdf] - [doc] - [xls] 10-K Annual Filings[2008.3.6] - [pdf] - [doc] - [xls]
■Praecis Pharmaceuticals,Inc[US]
- http://www.praecis.com/; 新薬ベンチャー 設立1993。従業員数146(2003末)。 [本社]米国Waltham, Massachusetts ●損益 ($000) 2003 2002 収入 - 1,029 純利益(純損失) (55,798) (46,075)
●Praecis Pharmaceuticals,Inc[US] ●http://www.plenaxis.com/ 前立腺癌薬 - Plenaxis Full prescribing information ●Research ★Product Pipeline ●Investors ★Financial Releases PRAECIS PHARMACEUTICALS INCORPORATED Reports Fourth Quarter and Year End 2003 Financial Results[2004.1.30] - Plenaxis 2004年売上見込$10.0-$20.0 million; 米国前立腺癌治療薬市場規模$1.2 Billion ★News ★Annual Reports ★SEC Filings
Presutti Laboratories, Inc.[US]
■Presutti Laboratories, Inc.[US]
設立 1998。 based in the northwest suburbs of Chicago. 詳細不明 Tindamax^(TM) (tinidazole) was recently divested to Mission pharmaceutical.
●Presutti Laboratories, Inc. - http://www.presuttilabs.com/ ; , Illinois Tindamax が新薬第一号で唯一の製品。 ●Products http://www.tindamax.com/ Tindamax[TM] U.S. Prescribing information[pdf] 本剤をオーファンドラッグとして開発していた。 ●News
■Procter &Gamble
- http://www.pg.com/; 従業員13.8万人 2006/6期 売上$68,222 Million うちHealthcare $8,964 million (12%)
●Procter &Gamble ■Investors ●Annual Reports ●SEC Filing Annual Filings 10-K[08/28/07] - [pdf]- [word] ●News ●P&G日本支社 - http://jp.pg.com/ ; 日本支社では医薬品は扱わない ニュースリリース～医薬品は除かれている 決算情報
●Procter &Gamble Pharmaceuticals - http://www.pgpharma.com/index.shtml ●P&GP Products Actonel ®(risedronate sodium tablets) - osteoporosis Asacol ® (mesalamine)Delayed-Release Tablets -ulcerative colitis Dantrium ® (dantrolene sodium) Capsules Dantrium ® IV (dantrolene sodium for injection) -Malignant hyperthermia (MH), Didronel ® [etidronate disodium] - osteoporosis Enablex ® (darifenacin) Extended Release Tablets -urge urinary incontinence (UUI) Macrobid ® (nitrofurantoin monohydrate/macrocrystals) Capsules Macrodantin ® (nitrofurantoin macrocrystals) ●News Archives ●Clinical Trials
■Progenics Pharmaceuticals Inc.[US]
- http://www.progenics.com/index.cfm ; NASDAQ:PGNX 1986.12 創立 unmet medical needs of patientsの革新的新薬の開発と商品化を目的とする バイオ製薬企業 Paul J. Maddon M.D., Ph.D.,CEO(コロンビア大Adjunct Assistant Professor)が設立。 1996.10 NASDAQ上場 2005.12 UR Labs, Inc(Relistorの権利保持)を買収。($18.7 million) 同社は、創立後１０年で株式公開、２２年目の2008年に初の新薬を発売した。 創薬ベンチャーの一典型である。 しかし第１号製品まで２０年以上を要したのは、複数プロジェクトを並行しながら、開発失敗を経た結果 そうなったという事。 ●会社決算合弁会社PSMA LLCは、2006.4.20 Cytogen社の持ち分買収。 ●Pipeline
($ 000) 2007 2006 2005 2004 2003 2002 2001 備考 (協力社から研究開発費) 65,455 58,415 - - - - - Wyeth (合弁会社から研究開発費) - - 988 2,,008 2,486 5,298 199 PSMA LLC (研究Grant/契約) 10,075 11,418 8,432 7,483 4,826 4,544 4,244 NIH(癌・HIV) (製品売上) 116 73 66 85 145 49 43 研究用試薬 収入 合計 75,646 69,906 9,486 9,576 7,461 10,085 8,883 営業利益 (51,458) (29,319) (71,527) (42,767) (31,607) (24,095) (15,049) 経常利益 (43,688) (21,618) (69,228) (42,018) (30,986) (20,789) (1,898) 当期純利益 (43,688) (21,618) (69,429) (42,018) (30,986) (20,789) (1,898) 研究開発費 95,123 61,711 43,419 35,673 26,374 23,761 14,501 取得研究開発費 - 13,209 - - - - - ライセンス料 1,053 390 20,418 390 867 - - 経費 合計 127,104 99,225 81,013 52,343 39,068 34,180 23,932 従業員数[連結] 245(研開200) 191(研開151) 149(研開124) 136(研開100) 115(研開83) 100(研開71) 80(研開59) ●研究開発費内訳 MNTX(RELISTOR) 41,500 32,100 43,800 19,700 11,700 7,000 - HIV 29,000 15,800 11,700 8,300 7,500 7,300 9,800 癌 16,100 23,200 6,600 5,900 4,500 7,000 4,200 その他 9,600 4,200 1,700 2,200 3,500 2,500 500 計 96,200 75,300 63,800 36,100 27,200 23,800 14,500 
●RELISTOR(R)メチルナルトレキソン臭化物（methylnaltrexone bromide 、MNTX） 皮下注射剤 難治性便秘 MNTXは、末梢のμオピオイド受容体に拮抗し、麻薬性鎮痛薬の鎮痛効果に影響を及ぼすことなく、麻薬性鎮痛薬の使用に伴う難治性の便秘を緩和します。 2008年4月、米国食品医薬品局（FDA）はRELISTOR(R)（methylnaltrexone bromide）皮下注射剤を、「既存の下剤による治療が十分でない末期癌患者等の緩和ケア患者における麻薬性鎮痛薬使用に伴う難治性便秘の治療」の適応症で承認しました。2008年6月より、プロジェニックス社とその欧米のパートナーであるワイス社がMNTXの皮下注製剤を「RELISTOR(R)」の商品名で、米国にて販売しております。また本剤は、2008年7月に欧州医薬品審査庁（EMEA）で承認を受け、欧州連合内の27の加盟国およびアイスランド、ノルウェー、リヒテンシュタインで承認されております。Progenics Pharmaceuticals, Inc
MNTXはUniversity of Chicagoが創製し、これをUR Labs, Inc.(2005.12Progenics社が買収)にライセンスし、更にUR Labs, Inc.は2001年10月Progenics社に全世界独占権をサブライセンスしたもの。
Wyeth and Progenics Pharmaceuticals Announce Worldwide Collaboration to Develop and Commercialize Methylnaltrexone[2005.12.23]
-Wyethは全世界の開発権を獲得、Progenicsは米国販売権のオプションを持つ。契約金は$60 million、以降最大$356.5 millionのマイルストーン支払い。【2007】2008年10月16日、Progenics Pharmaceuticals社はは小野薬品工業にRELISTORをライセンス。 2008年7月3日、Wyeth（ワイス）社とProgenics Pharmaceuticals社は、末期患者のオピオイド誘発性便秘の治療としてμオピオイド受容体アンタゴニスト・RELISTOR (メチルナルトレキソン；methylnaltrexone bromide) 皮下注射製剤がヨーロッパで承認されたと発表しました。 2008年5月22日、Wyeth（ワイス）社とProgenics Pharmaceuticals社は、術後腸閉塞を対象にしたRELISTOR (methylnaltrexone bromide) 静注製剤の第3相試験でプライマリーエンドポイントもセカンダリーエンドポイントも達成できなかったと発表しました。 2008年4月24日、Progenics Pharmaceuticals社とWyeth（ワイス）社は、緩和治療をうけている末期疾患患者の下剤無効オピオイド誘発性便秘の治療としてRELISTOR (methylnaltrexone bromide、メチルナルトレキソン) 皮下注射剤がアメリカFDAに承認されたと発表しました。 2008年4月24日、RELISTORはオピオイド誘発性便秘の治療でEMEA承認勧告。 2008年4月1日、RELISTORはカナダで承認。 2008年3月12日、RELISTORの術後イレウスＰ３試験の中間報告。 2008年1月10日、Wyeth（ワイス）社とProgenics Pharmaceuticals社は、特定の安全性データの更なるレビューのために、オピオイドによる便秘の治療薬候補・皮下注射メチルナルトレキソン（subcutaneous methylnaltrexone）のFDA承認審査期間が3ヶ月間延長されたと発表しました。 2007年7月20日、Wyeth Pharmaceuticals社とProgenics Pharmaceuticals社は、薬物依存の治療に使用されるオピオイド・メタドンを服用している患者を対象にした第1相試験でmethylnaltrexone（メチルナルトレキソン、MNTX）の新規経口製剤の便通促進効果が確認できたと発表しました。 2006年8月22日、Wyeth Pharmaceuticals社とProgenics Pharmaceuticals社は、オピオイドで慢性疼痛が治療されている患者のオピオイドによる便秘の治療薬として開発されている経口methylnaltrexone（メチルナルトレキソン）の第2相試験を開始したと発表した。 RELISTOR www.relistor.com 【2007競合】There are currently no FDA-approved products for reversing the debilitating side effects of opioid pain therapy (and specifically, opioid-induced constipation) or for the treatment of post-operative ileus, to which RELISTOR is directed. We are, however, aware of a product candidate that targets these therapeutic indications. This product, Entereg(TM) (alvimopan), is under development by Adolor Corporation, in collaboration with an affiliate of GlaxoSmithKline plc. Entereg is in advanced clinical development and Adolor has received an approvable letter from the FDA for Entereg regarding the treatment of post-operative ileus . ●PRO 140 HIV治療薬 P1b 【2007】PRO 140 is a humanized monoclonal antibody designed to block HIV infection by inhibiting the virus' ability to bind to and enter immune system cells and initiate the viral replication process. We have designed PRO 140 to target a distinct site on the co-receptor CCR5 without interfering with CCR5’s role, which includes, in part, directing the migration of immune cells to sites of inflammation in the body. PRO 140 has shown promising activity in pre-clinical studies. In in vitro studies, PRO 140 demonstrated potent, broad-spectrum antiviral activity against more than 40 genetically diverse “primary” HIV viruses isolated directly from infected individuals. Single doses of a murine-based PRO 140 reduced viral burdens to undetectable levels in an animal model of HIV infection. In mice treated with murine PRO 140, initially high HIV concentrations became undetectable for up to nine days after a single dose. Additionally, multiple doses of murine PRO 140 reduced and then maintained viral loads at undetectable levels for the duration of therapy in an animal model of HIV infection. Sustaining undetectably low levels of virus in the blood is a primary goal of HIV therapy.
In mid-2005, we completed a phase 1 study of humanized PRO 140 designed to evaluate the tolerability, safety, pharmacology and immunogenicity of PRO 140 in healthy volunteers. PRO 140 was generally well tolerated at all dose levels in this study. In February 2006, we received “Fast Track” designation from the FDA for PRO 140.
In December 2006, we completed enrollment and dosing in a phase 1b clinical trial of PRO 140. This clinical trial was designed to assess the tolerability, pharmacokinetics and preliminary antiviral activity of PRO 140 in 39 HIV-positive individuals. This multi-center, doubleblind, placebo-controlled, dose-escalation study was conducted in individuals who had not taken any anti-retroviral therapy within the previous three months and who had HIV plasma concentrations greater than or equal to 5,000 copies/mL. Subjects received a single intravenous dose of study medication . either placebo or one of three increasingly higher doses of PRO 140. PRO 140 blood levels and CCR5 coating were determined and compared with antiviral effects measured as changes in plasma HIV viral load following treatment. In May 2007, we announced positive results from this trial. Subjects receiving a single 5.0 mg/kg dose of PRO 140, which was the highest dose tested, achieved an average maximum decrease of viral concentrations in the blood of 98.5% (1.83 log 10 ). In these infected individuals, reductions in viral load of greater than 90% (1.0 log 10 ) on average persisted for two to three weeks after dosing. In addition, PRO 140 was generally well tolerated in this phase 1b proof-of-concept study.
In May 2007, we announced positive results from a phase 1b trial of an intravenous formulation of our monoclonal antibody, PRO 140, in HIV-infected individuals. We are also investigating a subcutaneous formulation of PRO 140 with the goal of developing a long-acting, self-administered therapy for HIV infection. In January 2008, we initiated the phase 2 clinical program for PRO 140, which will involve both the intravenous and subcutaneous formulations.●PMSA抗体医薬結合 前立腺癌 前臨床 【2007】In the area of prostate cancer, we are developing a human monoclonal antibody-drug conjugate, consisting of a selectively targeted cytotoxic antibody directed against prostate specific membrane antigen (“PSMA”), a protein found on the surface of prostate cancer cells. We are also developing vaccines designed to stimulate an immune response to PSMA. Our PSMA programs are conducted through our wholly owned subsidiary, PSMA Development Company LLC (“PSMA LLC”), which prior to April 2006 was a joint venture with Cytogen Corporation (“Cytogen”).
In February 2001, our joint venture with Cytogen entered into a worldwide exclusive licensing agreement with Abgenix to use Abgenix’XenoMouse(TM) technology for generating fully human antibodies to the joint venture’s proprietary PSMA antigen.●GMK Vaccine 黒色腫 P3中止 【2007】In the second quarter of 2007, we discontinued our GMK melanoma vaccine program. An independent data monitoring committee recommended that treatment in the European-based phase 3 trial, which began in 2001, be stopped because lack of efficacy was observed after an interim analysis. We have subsequently terminated our license agreement with Memorial Sloan-Kettering Cancer Center relating to this program. 【2003】GMK is a proprietary therapeutic vaccine that is designed to prevent recurrence of melanoma in patients who are at risk of relapse after surgery. We hold a worldwide exclusive license to GMK from Sloan-Kettering Institute for Cancer Research. We are currently conducting two phase 3 clinical trials of GMK. GMK is composed of the ganglioside GM2 joined to the carrier protein keyhole limpet hemocyanin, or KLH, and combined with the adjuvant QS-21. QS-21 is a compound in the Stimulon. family of adjuvants developed and owned by Aquila Biopharmaceuticals, Inc., a wholly owned subsidiary of Antigenics, Inc.. GMK is designed to stimulate the immune system to produce specific antibodies to the ganglioside antigens. These antibodies have been shown in vitro to recognize and destroy cancer cells. Based on the in vitro results and the clinical trial results described below, we believe that vaccination of cancer patients with ganglioside conjugate vaccines may delay or prevent recurrence of cancer and prolong overall survival. ●資金調達 【2007】We have, to date, generated no meaningful amounts of product revenue, and consequently we have relied principally on external funding to finance our operations. We have funded our operations since inception primarily through private placements of equity securities, payments received under collaboration agreements, public offerings of common stock, funding under government research grants and contracts, interest on investments, the proceeds from the exercise of outstanding options and warrants and the sale of our common stock under our Employee Stock Purchase Plans. At December 31, 2007, we had cash, cash equivalents and marketable securities, including non-current portion, totaling $170.4 million compared with $149.1 million at December 31, 2006. Our existing cash, cash equivalents and marketable securities at December 31, 2007 are sufficient to fund current operations for at least one year. Our cash flow from operating activities was negative for the years ended December 31, 2007, 2006 and 2005 due primarily to the excess of expenditures on our research and development programs and general and administrative costs related to those programs over cash received from collaborators and government grants and contracts to fund such programs, as described below. 【2003】We have funded our operations since inception primarily through three public offerings of common stock, private placements of equity securities, payments received under collaboration agreements, funding under government research grants and contracts, interest on investments, a line of credit that was repaid and terminated and the proceeds from the exercise of outstanding options and warrants. In November 2003, we completed a public offering of 3.33 million shares of our common stock at a price of $16.25 per share. The managing underwriters for this offering were Citigroup, CIBC World Markets Corp., Lazard, Legg Mason Wood Walker, Incorporated and Punk, Ziegel & Company. Net proceeds to the Company after expenses were $49.8 million. We are using the proceeds from the offering for the funding of clinical trials of product candidates, expansion of our manufacturing facilities and research and development projects as well as for working capital and other general corporate purposes.
At December 31, 2003, we had cash, cash equivalents and marketable securities, including non-current portion, totaling $65.7 million compared with $42.4 million at December 31, 2002. The cash used in operations for the year ended December 31, 2003 was $27.4 million compared with $17.3 million for the same period in 2002. The increase in cash used in operations for the year ended December 31, 2003 resulted primarily from higher net losses resulting from increased research and development activity in connection with MNTX, partially offset by an increase in accounts payable and accrued expenses.● 【】
●Progenics Pharmaceuticals Inc.[US] ●Products ★RELISTOR(methylnaltrexone bromide) 便秘 ★Pipeline ■Investor Relations ●SEC Filings 10-K annual report[Mar 17, 2008] - [pdf] - [doc] - [xls] ●Annual Reports ●Company News
■Prometheus Laboratories Inc[US]
- http://www.prometheuslabs.com/Default.asp 設立 California in December 1995 ●会社決算
($ 000) 2007 2006 2005 2004 2003 2002 2001 備考 売上高 220,940 187,411 138,943 89,601 69,588 ～医薬品 143,655 119,150 83,965 38,874 30,537 ～臨床試験事業 77,285 68,261 54,978 50,727 39,051 営業利益 56,370 55,771 39,205 (26,241) 11,112 経常利益 26,611 54,513 34,502 (35,708) 1,984 当期純利益 4,318 32,239 28,944 (35,737) 3,953 研究開発費 13,024 4,622 3,712 5,275 8,044 製品権利獲得
割賦償還3,255 3,255 3,255 4,335 5,432 従業員数[連結] Entocort EC 110,848(+30) 85,123(+85) 46,064 [budesonide]クローン病 Lotronex 2,471(-) - - - - - - [alosetron HCl]過敏性腸症候群(IBS);発売2007.11.1 Non-Promoted 30,336(-11) 34,027(-10) 37,901 mercaptopurine等 医薬品売上 計 143,655(+21) 119,150 ●販促を行わない製品群の個別製品売上 Imuran 7,700 8,400 9,000 [azathioprin]腎移植免疫抑制剤、関節リウマチ Helidac Therapy 10,400 11,100 9,400 [Bismuth Subsalicylate] H.pylori 除菌(H2拮抗剤と併用) Ridaura 3,900 3,700 3,900 [auranofin]関節リウマチ Mercaptopurine 6,500 9,000 13,400 [Mercaptopurine]リンパ性白血病 その他 1,900 1,900 2,200 []
Entocort EC(budesonide) クローン病 2005年1月1日にAstraZeneca LPから米国の独占販売権を獲得し、期限は2010末迄。 [2007]
【競合】軽～中等度のクローン病治療のFDA承認を認可されているのはEntocort ECだけだが、医師はsulfasalazine or mesalamineのようなアミノサリチル酸、hydrocortisone or prednisoneのようなステロイドを経口で炎症抑制に使用している。 しかしステロイドは一般にニキビや顔面の膨れ等副作用が強いので短期使用。
重症度によってはazathioprine, mercaptopurine or methotrexateのような免疫抑制剤を使用する。 中等度～重症のクローン病にはinfliximab and adalimumab等の生物製剤を使用する。Entocort EC is the only FDA-approved drug indicated for the induction and maintenance of clinical remission in mild to moderate active Crohn's disease involving the ileum and/or the ascending colon. The ileum and/or the ascending colon are affected in approximately 70% of Crohn's disease patients. Entocort EC consists of an encapsulated formulation of budesonide granules, a glucocorticosteroid. Entocort EC is designed to release primarily in the ileum and/or the ascending colon, so that as little as 10% of the drug enters systemic circulation. Entocort EC may benefit patients by reducing glucocorticosteroid-related side effects. In addition, studies have shown that Entocort EC can provide symptom control for flares that is not statistically different from prednisolone (a steroid used to treat Crohn's disease) at eight weeks. Entocort EC is also approved for long-term maintenance therapy for many people with mild to moderate Crohn's disease.
We believe Entocort EC competes on perceived value based on relative cost, product efficacy and safety. Entocort EC prescriptions have increased approximately 73.5% in 2007 over 2004, the year before we began selling the product, in a relatively flat market during the same period. Since we acquired promotion and distribution rights to Entocort EC, we have increased Entocort EC's share of the prescription market defined to include Entocort EC and the 5-ASAs from 6.1% in January 2005 to 9.2% in March 2008. We have priced Entocort EC treatment based on its value as the only approved product for the treatment of mild to moderate Crohn's disease, and its value relative to competing therapies.
LOTRONEX 錠(alosetron HCl) 過敏性腸症候群(IBS) GlaxoSmithKlineから米国の独占販売権を獲得(2008.1契約)、2007年11月販売開始。 There are five U.S. patents covering Lotronex, including a compound patent which expires in January 2013 and method of use patents which expire in October 2018. [2007]
【競合】IBSのFDA承認を認可されているのは３製剤のみ。 まずLotronexで、重症の下痢を主症状とするIBSの女性患者に認可されている唯一の薬剤。
２番目がZelnorm(R) (tegaserod maleate)で、米国では2007年に市場回収され、現在は生命にかかわる患者に対する治験用としてのみ使用。
３番手がAmitiza(R) (lubiprostone)で、2008年4月に１８才以上の女性の便秘型IBS治療でFDA承認。Prior to our acquisition of the exclusive rights to Lotronex in the United States, GlaxoSmithKline voluntarily withdrew Lotronex from the market in 2000 after failing to reach agreement with the FDA on how to best manage risks associated with the product. The FDA approved a supplemental NDA for Lotronex in 2002 with a more limited indication and a special warning referred to as a "black box" warning and it was subsequently re-introduced to the market. In order to reduce the potential for serious side effects of Lotronex, it is subject to a special prescribing program designed to ensure that only doctors who have enrolled in the Prescribing Program for Lotronex^(TM) write prescriptions for it. As of April 30, 2008, approximately 9,000 physicians in the United States were enrolled in the prescribing program. In connection with their enrollment into the prescribing program, the physicians must have an understanding of IBS and be familiar with the side effects and risks of Lotronex.
Since reintroduction of Lotronex in 2002, no lawsuits involving Lotronex have been filed against GlaxoSmithKline relating to adverse side effects of the product. Under our agreement to purchase Lotronex, we are not liable for claims related to Lotronex that arose prior to the date of the acquisition.
[2007]
●Prometheus Laboratories Inc[US] ●Products and Services ●News Releases Prometheus to Acquire Lotronex(R) From GlaxoSmithKline[2007.11.7] ENTOCORT(R) EC (budesonide) Capsules Recommended by the American Gastroenterology
Association as First-Line Therapy for the Treatment of Mild-to-Moderate Crohn's Disease[2006.6.5] Prometheus Announces FDA Approval For Additional Indication Of ENTOCORT(R) EC (Budesonide) Capsules[2005.5.10] Prometheus Launches ENTOCORT(R) EC (Budesonide) Capsules[2005.1.11] Prometheus Laboratories to Market Entocort(R) EC[2004.12.1] - AstraZenecaから米国販売権獲得。 販売は2005.1から。 AstraZenecaの2004年度Entocort(R) EC売上高は$30 million。 2001.11から販売されていた。 ●SEC Filings S-1/A, Securities Registration Statement[05/15/2008]
■ProStrakan Group plc[スコットランド]
- http://www.prostrakan.com/index.html 2004.12.1 Elfar 買収 2004.01.14 OTL Pharma 買収 ★子会社(2007末) Strakan International Ltd /Bermuda Licensing and commercialisation of pharmaceuticals Strakan Pharmaceuticals Ltd* /England Development and registration of pharmaceuticals ProStrakan Ltd* /England Registration, marketing and sale of pharmaceuticals Strakan GS Ltd /England Trustee for ProStrakan Group Employee Benefit Trust ProStrakan Pharma SAS* /France Registration, marketing and sale of pharmaceuticals ProStrakan Farmaceutica SLU* /Spain Marketing and sale of pharmaceuticals Arzneimittel ProStrakan GmbH* /Germany Marketing and sale of pharmaceuticals ProStrakan Pharma BV* /Netherlands Marketing and sale of pharmaceuticals ProStrakan AB* (50%) /Sweden Marketing and sale of pharmaceuticals ProStrakan Inc* (formerly Strakan Life Sciences Inc.) /US Registration, marketing and sale of pharmaceuticals * investment held indirectly ●会社決算●製品売上高
(￡ 000) 2007 2006 2005 2004 2003 2002 2001 売上高 45,596 38,459 売上原価 16,204 15,445 粗利益 29,392 23,014 流通コスト 26,164 21,455 管理費 10,992 9,127 その他経費 (99) 23 開発費 10,060 10,700 営業利益 (17,725) (18,291) 経常利益 (17,605) (17,318) 当期純利益 (17,348) (29,590) 従業員数[連結] 217 279
(￡million) 2007 2006 2005 2004 2003 備考 売上高 45.596 38.459 AdcalD3 14.8(+14) 13.0 10.1 6.8 3.7 [経口Ca&VD3]骨粗鬆症 Isotard XL 4.9(+7) 4.6 4.2 4.3 3.5 [Isosorbide mononitrate] Droperidol欧 4.3(+17) 3.6 3.3 2.8 2.3 [Droperidol]注射剤；術後めまい・嘔吐の予防・治療剤 Rectogesic欧 3.4(+87) 1.8 0.6 [nitroglycerin軟膏]肛門痛;米Cellegesic 2009発売予定 Tostran/Itnogen/Tostrex欧 0.6(+256) [経皮testosterone gel]米Fortigel 2009発売予定
●Sancuso(transdermal patch granisetron) 【2007】FDA承認2008.9.15;欧申請2007.7.16 ●Rapinyl/Abstral(sub-lingual tablet fentanyl) 疼痛 【2007】;スエーデンOrexo ABから欧州独占権獲得。[2005.12.21];
米国ライセンスを持つEndo Pharmaceuticals Incによる米国P3RCT中間報告[2007.12.17]よるとRapinylは優れた結果を示した。この時点ではEMEAで審査中。;スエーデンで承認2008.3.7;
●ProStrakan Group plc[スコットランド] - http://www.prostrakan.com/ - 協和醗酵キリンの子会社[2011.4.21] - [2011..4.20] ●Products ●Development～パイプライン <--- ●Investor Relations ★Press Releases ★Annual Report Annual Report 2007[pdf,80p] ---> ●Media Center - News ProStrakan Receives FDA Approval for Rectiv for the Treatment of Moderate to Severe Pain Associated with Chronic Anal Fissures[2011.6.22]～Rectiv&trade (nitroglycerin) Ointment 0.4%
ProStrakan Group Announces Canadian Launch of Abstral[2011.6.14]
～Abstral is a novel, rapidly-disintegrating, sublingual (under the tongue) formulation of fentanyl, a well-established opioid used for the management of breakthrough pain for cancer patients already receiving, and tolerant to, opioid analgesics for chronic pain. Abstral will be promoted in Canada alongside Paladin’s other pain products which include: Tridural®, Metadol® and Pennsaid®.
ProStrakan outlicensed the Canadian rights to Paladin in December 2008 and Abstral was granted Canadian regulatory approval in February 2011.
Abstral is already marketed by ProStrakan across the principal European markets and was launched earlier this year in the United States. In the top four European markets, Abstral achieved a 24% market share by tablet volume of short-acting fentanyl products (Source: IMS data February 2011).
Abstral Approved by Health Canada[2011.2.22]～Paladin Labs Inc(2008.12ライセンスアウト契約)販売予定
ProStrakanはOrexo ABから北米および欧州のライセンス契約取得
Trading Update and US FDA Approval of Abstral[2011.1.7]
ProStrakan Announces Canadian Regulatory Filing of Abstral[2010.2.4]
ProStrakan Announces FDA Acceptance of Abstral Filing[2009.10.6]
ProStrakan Announces Upcoming Launch of Abstral in France[2009.6.30]
Abstral Receives Marketing Approval in France and Spain[2009.3.2]
---------------------------------------------- ProStrakan Announces Outlicensing of Abstral(R) and Sancuso(R) in Canada[2008.12.22] ProStrakan Announces NewBridge Pharmaceuticals as Partner for Sancuso in the Middle East and Africa [2008.11.6] ProStrakan Launches Sancuso in US[2008.11.3] ProStrakan Receives US FDA Approval for Sancuso [2008.9.15] ProStrakan and JapanBridge Partner to Develop Sancuso in Japan, China & Parts of SE Asia[2008.5.23] - ジャパンブリッジKK under MPM Capital ProStrakan Announces Filing of MAA for Sancuso(R)[2007.7.16]
■PTC Therapeutics,Inc[US]
- http://www.ptcbio.com/big/indexhome.html 設立 1998 従業員100人 遺伝子転写後の制御プロセスをターゲットにした経口低分子化合物の研究、開発、販売に特化・2005.4.21 Muscular Dystrophy Association (MDA)から$1.5 millionのgrant獲得 (PTC124に関して) ・2005.2.23 Cystic Fibrosis Foundation (CFF)から$1.7 millionのgrant獲得
治験コード 段階 適応 作用 備考 PTC124 P2(05.12開始、06.12終了予定;24例) Duchenne muscular dystrophy (DMD)(ナンセンス変異によるデュシエンヌ型筋ジストロフィー);DMD(世界２万人)の15% 2005.7 EMEAオーファン指定
PTC124はナンセンス変異を目標とする経口薬。 ナンセンス変異は遺伝子内の遺伝暗号が変化し、翻訳が変異部位で中断・終了してしまい、結果として完全な蛋白が合成されず形質の変異が起こること。 PTC124はナンセンス変異を隠す遺伝病モデルでサイズ・機能面で完全なタンパク質に復元する能力を示す。P2(05.9開始、0610終了予定;24例) cystic fibrosis(ナンセンス変異による嚢胞性線維症);CF(米３万人)の10% 2004.12 FDAオーファン指定
2005.7 EMEAオーファン指定
2005.4.1 FDA FastTrack指定PTC299 P1a(2006.4開始) 癌
●PTC Therapeutics,Inc[US] ●Research and Development ●News PTC Therapeutics Announces Interim Phase 2 Results of PTC124 in Cystic Fibrosis[2006.4.4] PTC Therapeutics Receives Fast Track Designation for PTC124 in the Treatment of Duchenne Muscular Dystrophy[2006.3.30] - FDAの優先審査(通常１０か月を６か月)指定を認可。 European Medicines Agency (EMEA) Grants PTC Therapeutics Orphan Drug Designation
for PTC124 for the Treatment of Duchenne Muscular Dystrophy and Cystic Fibrosis[2005.7.7] ■PTC124治験プロトコール [ClinicalTrial.Gov]:Safety and Efficacy Study of PTC124 in Duchenne Muscular Dystrophy [ClinicalTrial.Gov]: PTC124 for Cystic Fibrosis [ClinicalTrial.Gov]: Safety and Efficacy of PTC124 for Cystic Fibrosis ■一般ニュースから Cystic Fibrosis Foundation Therapeutics, Inc. Awards $1.7 Million to PTC Therapeutics
for Development of PTC124 to Treat Cystic Fibrosis[2005.2.23] [EDGAR Online Pro]PTC THERAPEUTICS, INC MDA Research | PTC124 Trial Now Open to Boys With Duchenne Muscular Dystrophy Who Have Nonsense Mutations[2005.12.12] ■解説 [デュシェンヌ型筋ジストロフィー]
Duchenne型筋ジストロフィーはdystrophin遺伝子の変異によっておこる最も頻度が高く重症の筋ジストロフィーであり１０歳頃に独立歩行が困難となる。DMDのモデルマウスであるmdxマウスではdystrophin蛋白の欠損がみられる。mdxマウスやDMD患者においてはdystrophinの発現はrevertantな筋繊維の中に貯えられていて、これは変異を含んでいるexonのskippingが起こることによってin-frameの短い転写産物をつくり出されることに起因する。[ナンセンス変異 Nonsense mutations]
遺伝子の変異によって遺伝子内の遺伝暗号が変化し、アミノ酸に該当しない無意味（ナンセンス）なコドンが生じ、翻訳が変異部位で中断・終了してしまい、結果として完全な蛋白が合成されず形質の変異が起こること。[コドン Codon]
DNAあるいはメッセンジャーRNA上の3つの連続したヌクレオチドで表されたアミノ酸を指定する遺伝暗号（genetic code）[ジストロフィン]
筋肉の細胞膜の細胞骨格を構成するたんぱく質です。デュシェンヌ型筋ジストロフィーはジストロフィン遺伝子の変異によって細胞膜が不安定になり、結果的に筋繊維の壊死・萎縮が引き起こされると考えられています。細胞骨格系の異常という障害部位の特性から、現在のところ遺伝子治療が最も期待されている治療法とされています。
全身の筋細胞に存在する異常ジストロフィンを正常なものに「永続的に」置き換えることが遺伝子治療の理想です。しかしながら、体の一部の骨格筋でも遺伝子治療によって機能が回復したり、進行を遅らせることが出来れば、患者さんにとって福音であり将来の希望につながると言えます。[国立精神・神経センター]筋疾患のいろいろ [社団法人 日本筋ジストロフィー協会]筋疾患百科事典 「 DNA チップによる遺伝性筋疾患の 分子病態解明」[pdf,62p] 筋ジス研究の最近の進歩と治療
■Purdue Pharma L.P.[US]
- http://www.purduepharma.com/ ; 本社Stamford, Connecticut 1892 Dr. John Purdue Gray and George Frederick Bingham が創立(The Purdue Frederick CompanY)。 1952 Dr. Raymond Sackler and Dr. Mortimer Sackler(現在のオーナー)が買収。 1991 Purdue Pharma L.P.を設立。 2002 Purdue Products L.P.を設立。これはShire Pharmaceuticals GroupのOTC製品群の買収に伴うもの。 現在次の４社。 全て株式非公開の私企業。 Purdue Pharma L.P. Purdue Pharmaceutical Products L.P. Purdue Products L.P. The Purdue Frederick Company グループ従業員総数2200人。
●Purdue Pharma L.P.[US] ●Our Products ※以下、処方箋薬のみリストアップ
■QLT Photo Therapeutics[Ca]
1981 Province of British Columbia, Canadaで創業。 photosensitizers利用PDT製品が最初。 2004.11.19 Atrix Laboratories, Inc. 社(DDR技術専門バイオ)買収。 ●会社決算●製品売上高
(USD milllion) 2005 2004 2003 2002 2001 2000 売上高 242.0 186.1 146.8 110.5 83.4 32.4 うち(製品売上高) 210.0 179.3 142.1 104.1 79.5 24.9 うち(ロイヤリティ) 19.9 2.3 - - - 0.7 うち(契約研究開発) 11.3 4.4 4.6 6.4 3.9 5.1 うち(提携契約収入) 0.7 - - - - 1.7 営業利益 (347.9) (155.4) 58.0 経常利益 (336.8) (148.8) 68.8 当期純利益 (325.4) (165.7) 44.8 13.6 71.5 4.4 研究開発費 74.6 50.1 44.9 42.3 42.9 32.8 取得研究開発費 236.0 - - - - 従業員数[連結] 438 ●収入セグメント [SEGMENTED INFORMATION]
(USD 000) 2005 2004 2003 2002 2001 2000 Visudyne by Novartis Ophthalmics 483,762 448,277 356,948 Visudyne -QLT分(50%) 153,379 139,342 107,642 Visudyne -QLT計上売上高 187,238 177,457 142,125 Eligard他の製品売上高 22,786 1,841 - QLT製品売上高 210,024 179,298 142,125
(USD 000) 2005 2004 2003 2002 2001 2000 Visudyne 187,238 177,457 142,125 Eligard 31,576 3,270 - Generic dermatology products 7,672 501 - Dental products 2,434 408 - Other 1,046 - - 契約研究開発 11,283 4,436 4,625 ライセンス 724 - - 収入 合計 241,973 186,072 146,750
●QLT Photo Therapeutics[Ca] - http://www.qltinc.com/ ●COMMERCIAL CENTER～製品 Visudyne(verteporfin)黄斑変性治療薬(Novartisブランド) Eligard(leuprolide acetate)前立腺癌治療薬(Sanofi-Aventisブランド) Generic dermatology Photofrin(porfimer sodium)光力学療法薬 ～June 8, 2000 QLTはAxcan Pharma Incに全世界権利売却 ●INVESTMENT CENTER ★SEC / Financial Reports - EDGAR SEC Filing QLT's Annual Reports on Form 10-K 2005 - Form 10K[2006.3.15] - [html] ★Annual Reports ●Financial News QLT Announces Visudyne Sales for Fourth Quarter and Fiscal Year 2005[2006.1.19] - Visudyne全売上2005年度 US$484 million (+8%) QLT Announces Year-End Results for 2001 and Provides Guidance for 2002[2002.2.6] - Visudyne全売上2001年度 $346.3 million +134.8%(US$223.3 million)。 うち米国は、63% (前年66%)を占める。 ●Other News ●2005年度 Visudyne is commercially available in more than 75 countries, including the U.S., Canada, Japan and the European Union countries, for the treatment of a form of wet AMD known as predominantly classic subfoveal choroidal neovascularization, or CNV, and in over 50 countries for the form of wet AMD known as occult subfoveal CNV. Visudyne is reimbursed in the U.S. by the Centers for Medicare & Medicaid Services for certain patients with the occult and minimally classic forms of wet AMD. It is also approved in more than 60 countries, including the U.S., Canada and the European Union countries, for the treatment of subfoveal CNV due to pathologic myopia (severe near-sightedness). In some countries, including the U.S. and Canada, Visudyne is also approved for presumed ocular histoplasmosis or other macular diseases. QLT develops and commercializes Visudyne through a co-development, manufacturing and commercialization agreement with Novartis Ophthalmics of Switzerland (a division of Novartis Pharma AG).
In addition to our lead commercial product Visudyne, we now market (through commercial partners) the Eligard R line of products for the treatment of prostate cancer, and a line of dermatology products. The Eligard product line includes four different commercial formulations of our Atrigel R technology combined with leuprolide acetate for the treatment of prostate cancer. The U.S. Food and Drug Administration, or FDA, has approved all four products: Eligard 7.5-mg (one-month), Eligard 22.5-mg (three-month), Eligard 30.0-mg (four-month) and Eligard 45.0-mg (six-month). The Eligard 7.5-mg and Eligard 22.5-mg products are also approved in a number of other countries, including most European countries, Canada, Australia, New Zealand and a number of Latin American countries. In addition to the U.S., Eligard 3.0-mg (four-month) and Eligard 45.0-mg (six-month) are also approved in Canada, Australia and New Zealand. However, in connection with the ongoing patent litigation commenced by TAP Pharmaceuticals, Inc. and its co-plaintiffs in the United States and Canada, the marketing partner for Eligard in the United States, Sanofi-Sythelabo, Inc. or Sanofi-Synthelabo, has suspended the sales of Eligard in the United States from early March 2006 to May 1, 2006 (see Item 3. Legal Proceedings).
Our efforts to increase our portfolio of products are ongoing. We also have a number of product candidates that utilize the Atrigel drug delivery system in our pipeline. We carry out research and pre-clinical projects in our core therapeutic area of ophthalmology, and other areas such as dermatology. We also conduct contract research and development work on product candidates of third parties using the Atrigel drug delivery system in a number of therapeutic areas from which we can potentially derive royalty revenue upon commercialization.
Our portfolio of dermatology products consists of both proprietary and generic products that are commercialized, under regulatory review, or in various stages of development. Our most advanced proprietary dermatology product, Aczone?, was approved by the FDA in July 2005. Although Aczone is approved in the U.S, it is not yet marketed. A decision with respect to the commercialization of Aczone is pending the outcome of an additional Phase IV clinical study and submission to the FDA to remove a restriction currently on the approved label for the product (see Item 1. Business - Our Approved Products - Aczone). Our generic dermatology business, which is part of a development and commercialization arrangement with Sandoz, Inc., currently comprises seven approved products, six of which are currently marketed, two additional ones that are tentatively approved (final approval pending patent expiration of the original compounds) and four products under regulatory review. To further focus our business on the research and development of proprietary products in our core therapeutic areas, we have previously announced that we are planning to divest our non-core dermatology assets, including the generic dermatology business and our manufacturing facilities associated with the dermatology business.
■Q-Med AB[SW]
- http://www.q-med.com/ 1987設立。ヒアルロン酸商品化のためBengt Agerupにより。 世界６０カ国で販売 1996年末 最初の製品Restylane(皺取り用；ヒアルロン酸)が欧州で認可。 NASHA =Non-Aniaml Stabilized Hyaluronic Acid ●会社決算* 2004.3.14 [1 SEK=14円、0.1299USD} 607.4SEK Million=85億円 ●製品売上
(SEK milllion) 2005 2004 2003 2002 2001 2000 1999 備考 売上 976.0(+19) 823.2 607.4 517.8 380.2(+60) 237.2 143.7 粗利益 835.8(+16) 719.7 527.7(+13) 466.3 343.2(+62) 212.1(+91) 111.1 営業利益 111.7(-68) 345.2 821.0 9.5 23.7(-30) 33.7(+148) 13.6 経常利益 123.9 361.8 832.3 0.6 35.4(-20) 44.0(+252) 12.5 純利益 77.1 257.8 845.3 -3.6 35.3 35.1 15.7 研究開発費 201.4(+6) 189.7 166.1(+5) 157.5 122.1(+109) 58.5 従業員数 525 504 450 369 266 197 110 うちスエーデン 354 334 297 255 177 138 * 2004.3.14 [1 SEK=14円、0.1299USD} 607.4SEK=85億円 * Nuova ICT(エステ製品専業販売)を2001.9買収。 * Restylane - 同社第一号製品で、先ず欧州1996.9発売、2000.3にRESTYLANE Fine Lines and PERLANE. を発売。 70ヵ国で販売。 - 日本 1999.5 申請 対抗品Zyplastとの比較臨床試験実施 * DEFLUX - dextranomer+NASHAを含むゲル。1998年欧州でvesicoureteral refluxの適応で承認。 1999年stress urinary incontinence in womenで追加承認。
(SEK milllion) 2005 2004 2003 2002 2001 2000 1999 備考 売上 713.3(+9) 652.8 607.4 517.8 380.2 237.2 143.7 Esthetic 713.3(+9) 652.8 500.9(+9) 458.6(+24) 371.2(+59) 233.8(+87) 124.8 Restylane 713.3(+9) 652.8 500.9 458.6 371.2(+59) 233.8(+87) 124.8 (hyaluronate)しわ取り HospitalCare 262.7(+54) 170.4 106.5 59.2 9.0 3.4 2.1 (泌尿器) 92.0 51.4 9.0 (dextranomer)尿失禁 Zuidex 29.3(+46) 20.1 (dextranomer)尿失禁;発売2002.末 Deflux 178.4(+47) 121.6 9.0 3.1 2.1 (dextranomer)小児Vesicoureteral reflux[VUR]膀胱尿管逆流 Durolane 55.0(+91) 28.7 14.5 7.8 0.0 0.3 0.0 (hyaluronate)リウマチ
●Q-Med AB - http://www.q-med.com/ ●Our Technology ●Investors ★Fiancial Reports 同社年報はヒアルロン酸の開発・市場レポートとしても優れている。 Annual Report 2005 Q-Med AB (publ)[2006.4.7;pdf,84p] Annual Report 2004[2005.3.18;pdf,68p] Annual Report 2003[2004.3.25;pdf,69p] Annual Report 2002[2003.3.25;pdf,60p] Annual Report 2001[2002.3.25;pdf,56p] Annual Report 2000[2001.3.28;pdf,56p] ★Financial Review ★Press Releases Year-End Report 2005[2006.2.10;pdf,12p] REPORT ON OPERATIONS 2004[2005.2.11;pdf,13p] REPORT ON OPERATIONS 2003[2004.2.12;pdf,11p] REPORT ON OPERATIONS 2002[2003.2.10;pdf,11p] Continued strong growth 2001[2002.2.8;pdf,11p] Q-Med's turnover up 87 percent 2000[2001.2.8] ●Press Room - Press Releases ★Press Releases 2006 ★Press Releases 2005 ★Press Releases 2004 ★Press Releases 2003 ★Press Releases 2002 ★Press Releases 2001 ●製品 Restylane -http://www.restylane.com/ (hyaluronic acid)しわ取り Zuidex -http://www.zuidex.com/ (dextranomer and NASHA-gel) 尿失禁治療薬 Deflux -http://www.deflux.com/ (dextranomer and NASHA-gel)尿失禁治療薬 Durolane -http://www.durolane.com/ (hyaluronic acid)変形性膝関節症薬注射
■Reckitt Benckiser plc[UK]
-http://www.reckitt.com/ ; 英国。1999年Reckitt & Colman plc とBenckiser N.Vが合併して現社名に ●会社決算 (￡m) 2004 2003 2002
純収入 3,871(+4) 3,713(+7) 3,454 営業利益 749(+12) 679(+18) 577 経常利益 770(+17) 660(+21) 545 純利益 586(+20) 489(+20) 408
従業員数 20.4千人 22.3 ●セグメント別売上高 (￡m) 2004 2003 2002
純収入 3,871(+4) 3,713(+7) 3,454
Fabric Care 1,064(+5) 1,017 884 衣料ケア(洗剤等) Surface Care 773(+3) 748 738 殺菌、洗剤 Dishwashing 542(+1) 535 480 皿洗い Home Care 564(+4) 540 523 ホームケア 保健用品 599(+11) 539 453 Health&Personal
Core事業 3,542(+5) 3,379 3,245 他Household 139(-1) 140 167
純収入～継続 3,681(+5) 3,519 3,245 ●地域別売上高 (￡m) 2004 2003 2002
純収入 3,871(+4) 3,713(+7) 3,454
欧州 2,032(+6) 1,909 北米・豪州 1,196(+0) 1,197 その他 643(+6) 607
●Reckitt Benckiser plc[UK] ●Newsroom ★Press Releases Reckitt Benckiser announces Full Year Results 2004[2005.2.9] ●Investor relations ★Financial Results - Annual reports Annual Report 2003[pdf,74p] ●Our Brands～カタログなし、概況説明 ★Health and Personal Care
■RECORDATI IND.CHIMICA FARM. S.P.A[IT]
従業員2000人以上。うち研究開発150人。 ●会社決算 (Euro 000) 2004 2003
収入 483,308(+0.2) 487,535 EBITDA 111,566(+3.5) 107,773 営業利益 90,425(+11.6) 81,030 純利益 53,964(+127.2) 30,217 ●収入内訳 (Euro 000) 2004 2003
収入 483,308(+0.2) 487,535
医薬品 438,876(+3.5) 424,041 医薬原料 49,432(-22.1) 63,494 イタリア 218,797(+3.4) 211,580 国際 269,511(-2.3) 275,955 ●製品別売上高 (Euro 000) 2004 2003
Zanidip 114,709(+25.4) 91,485 [lercanidipine]高血圧;Ca拮抗剤;/Lercadip 伊 39,491(+17.3) 33,674 仏 22,994(+49.1) 15,419 スペイン 4,944(+15.9) 4,267 Elopram/Entact [citalopram/escitalopram]うつ病 伊 50,971(+12.9) 45,139 /2003.11発売 仏 スペイン Peptazol [pantoprazole] 潰瘍 伊 23,546(+19.4) 19,719 仏 - スペイン 15,085(+6.6) 14,146 Ulcotenalの商品名 Tora-dol []鎮痛 伊 19,544(+1.7) 19,220 仏 スペイン Isocef [ceftibuten]抗感染 伊 13,605(-7.8) 14,753 仏 スペイン Acequin/Acequide []高血圧 伊 7,250(-15.6) 8,595 仏 スペイン Octegra [moxifloxacin] 抗感染 伊 6,779(+3.5) 6,547 仏 スペイン Hexa-line [] 伊 - 仏 15,246(-12.9) 17,509 スペイン Exomuc [] 伊 - 仏 11,714(-10.4) 13,070 スペイン Abufene [beta-alanine]更年期障害 伊 - 仏 8,407(+47.7) 5,693 スペイン Dermatrans [nitroglycerin TTS Patch]狭心症 伊 - 仏 - スペイン 1,644(+73.4) 948 Alergoliber [rupatadine]抗ヒスタミン lic from Uriach 伊 仏 スペイン 1,159(-) 0
●RECORDATI IND.CHIMICA FARM. S.P.A[IT] ●Pharmaceuticals lercanidipine, flavoxate, fenticonazole Product pipeline ■Investors Relations & Press Room ●Press Releases ●Annual Reports Annual Report 2004[pdf,78p]
■Regeneron Pharmaceuticals, Inc.[US]
●会社決算EYLEA製品売上 2011Q4=$24.8 million
($ 000) 2011 2010 2009 2008 2007 うち提携収入 369,681 386,725 314,457 185,138 87,648 うち製品売上 44,686 22,254 18,364 6,249 - うちライセンス料 24,858 40,150 40,013 40,000 28,421 うち契約研究など 6,599 6,945 6,434 7,070 8,955 収入 合計 445,824 459,074 379,68 238,457 125,024 営業利益 (205,159) (97,472) (74,103) (86,249) (115,373) 経常利益 (222,892) (104,468) (71,952) (76,778) (106,519) 当期純利益 (221,760) (104,468) (67,830) (79,129) (106,519) 研究開発費 529,506 489,252 398,762 274,903 202,468 従業員数[連結] 1,704
●EYLEA®(aflibercept)黄斑変性 【2011】 We, together with our ex-U.S. collaborator Bayer HealthCare, are evaluating EYLEA® in Phase 3 programs in patients with central retinal vein occlusion (CRVO), diabetic macular edema (DME), and choroidal neovascularisation (CNV) of the retina as a result of pathologic myopia. We plan on initiating a Phase 3 study in branch retinal vein occlusion (BRVO) in the first quarter of 2012. Wet AMD, diabetic retinopathy (which includes DME), and retinal vein occlusion are three of the leading causes of adult blindness in the developed world. In these conditions, severe visual loss is caused by a combination of retinal edema and neovascular proliferation. The Phase 3 trials in wet AMD, known as VIEW 1 and VIEW 2 ( V EGF Trap: I nvestigation of E fficacy and Safety in W et age-related macular degeneration), compared EYLEA® and Lucentis® (ranibizumab injection), a registered trademark of Genentech, Inc. Lucentis® is an anti-VEGF agent approved for use and the current standard of care in wet AMD. VIEW 1 was conducted in North America and VIEW 2 was conducted in Europe, Asia Pacific, Japan, and Latin America. The VIEW 1 and VIEW 2 trials both evaluated EYLEA® doses of 0.5 milligrams (mg) and 2.0 mg at dosing intervals of four weeks and 2.0 mg at a dosing interval of eight weeks (following three initial monthly doses), compared with Lucentis® dosed according to its U.S. label, which specifies doses of 0.5 mg administered every four weeks over the first year. The primary endpoint of these non-inferiority studies was the proportion of patients treated with EYLEA® who maintain visual acuity at the end of one year compared to patients dosed monthly with Lucentis® . Visual acuity is defined as the total number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart, a standard research tool for measuring visual acuity. Maintenance of vision is defined as losing fewer than three lines (equivalent to 15 letters) on the ETDRS chart. Secondary endpoints included the mean change from baseline in visual acuity as measured by ETDRS, the proportion of patients who gained at least 15 letters of vision at week 52, and the amount of fluid under the retina.
We and Bayer HealthCare announced week 52 results from the VIEW 1 and VIEW 2 studies in November 2010. In these studies, all regimens of EYLEA® , including EYLEA® dosed every two months, successfully met the primary endpoint of statistical non-inferiority compared to Lucentis® dosed every month. A generally favorable safety profile was observed for both EYLEA® and Lucentis® . The incidence of ocular treatment emergent adverse events was balanced across all four treatment groups in both studies, with the most frequent events associated with the injection procedure, the underlying disease, and/or the aging process. The most frequent ocular adverse events were conjunctival hemorrhage, macular degeneration, eye pain, retinal hemorrhage, and vitreous floaters. The most frequent serious non-ocular adverse events were typical of those reported in this elderly population who receive intravitreal treatment for wet AMD; the most frequently reported events were falls, pneumonia, myocardial infarction, atrial fibrillation, breast cancer, and acute coronary syndrome. There were no notable differences among the study arms.
Based on these positive results, we submitted a Biologics License Application (BLA) to the FDA in February 2011 for marketing approval of EYLEA® in wet AMD in the United States. In April 2011, the FDA accepted the BLA for filing and granted our request for Priority Review. In June 2011, the Dermatologic and Ophthalmic Drugs Advisory Committee of the FDA unanimously recommended that the FDA approve our BLA. In 2011, Bayer HealthCare submitted regulatory applications for marketing approval of EYLEA® in wet AMD in the European Union, Japan, and other countries. In November 2011, we received U.S. marketing approval from the FDA for EYLEA® Injection for the treatment of patients with wet AMD.
In December 2011, we and Bayer HealthCare announced Year 2 results from the VIEW 1 and VIEW 2 studies. In the second year of the studies, patients were treated with the same dose per injection as in the first year and were evaluated monthly to determine need for retreatment. Patients were treated at least every 12 weeks. All Year 2 analyses were considered exploratory. In an integrated analysis of the VIEW 1 and VIEW 2 studies, the visual acuity gain from baseline in the EYLEA® 2.0 mg every eight week group at week 96 was 7.6 letters compared to 8.4 letters at week 52, with an average of 11.2 injections over two years and 4.2 injections during the second year. The visual acuity gain from baseline in the monthly Lucentis® group at week 96 was 7.9 letters compared to 8.7 letters at week 52, with an average of 16.5 injections over two years and 4.7 injections during the second year. The results of each of the VIEW 1 and VIEW 2 studies were consistent with the integrated analysis.
The overall fewer average number of injections in the second year in the EYLEA® 2.0 mg every eight week group compared to the Lucentis® group (4.2 versus 4.7; nominal p<0.0001) was driven by the fact that fewer patients needed more intense therapy in the EYLEA® group and those patients required fewer injections.
The proportion of patients who required frequent injections (six or more) during Year 2 was lower in the EYLEA® 2.0 mg every eight week group compared to the Lucentis ® group (15.9% versus 26.5%). In the 25% of patients who required the most intense therapy (the greatest number of injections), patients in the EYLEA® 2.0 mg every eight week group required an average of 1.4 fewer injections in Year 2 compared to the Lucentis® group (6.6 versus 8.0). In the 25% of patients in each group who had the fewest number of injections in Year 2, the average number of injections was similar (approximately 3 for both groups, corresponding to the protocol-mandated minimum number of injections).
A generally favorable safety profile was observed for both EYLEA® and Lucentis® . The incidence of ocular treatment emergent adverse events was balanced across all four treatment groups in both studies. The most frequent ocular adverse events (greater than 10% of patients for the overall study population) were conjunctival hemorrhage, eye pain, retinal hemorrhage, and visual acuity reduced. The most frequent serious non-ocular adverse events were typical of those reported in this elderly population who receive intravitreal treatment for wet AMD; the most frequently reported events (greater than 1% of patients for the overall study population) were falls, pneumonia, myocardial infarction and atrial fibrillation. There were no notable differences among the study arms. The incidence of arterial thrombotic events as defined by the "Anti-Platelet Trialists" group criteria was 3.2% of patients for Lucentis® and 3.3% of patients in the combined EYLEA® groups.
In the fourth quarter of 2011, we and Bayer HealthCare initiated a Phase 3 trial, known as SIGHT, evaluating the efficacy and safety of EYLEA® in the neovascular form of wet AMD in China. EYLEA® will be evaluated for its effect on improving and maintaining vision when dosed as an intravitreal injection on a schedule of 2.0 mg every two months (following three initial monthly doses), as compared with Photodynamic Therapy (PDT) with verteporfin. After assessment of the primary endpoint at week 28, all patients, including those on PDT, will receive EYLEA® treatment until the end of the study at week 52. The trial will include approximately 300 patients and will be the largest retinal trial conducted in China. The SIGHT trial is being led by Bayer HealthCare.
EYLEA® was also in Phase 3 clinical studies for the treatment of CRVO, another cause of visual impairment. We led the COPERNICUS ( CO ntrolled P hase 3 E valuation of R epeated i N travitreal administration of VEGF Trap-Eye I n C entral retinal vein occlusion: U tility and S afety) study, and Bayer HealthCare led the GALILEO ( G eneral A ssessment L imiting I nfi L tration of E xudates in central retinal vein O cclusion with VEGF Trap-Eye) study. Patients in both studies receive d six monthly intravitreal injections of either EYLEA® at a dose of 2.0 mg or sham control injections. The primary endpoint of both studies was improvement in visual acuity versus baseline after six months of treatment as measured by the ETDRS eye chart. At the end of the initial six months, patients were dosed on an as-needed (PRN) basis for another six months. All patients were eligible for rescue laser treatment. In the COPERNICUS study, patients who were randomized to sham injections in the first six months were eligible to cross over to EYLEA® PRN dosing in the second six months.
In December 2010, we and Bayer HealthCare announced that in the COPERNICUS study, EYLEA® demonstrated a statistically significant improvement in visual acuity at six months compared to sham injections, the primary endpoint of the study. In this study, 56.1% of patients receiving EYLEA® gained at least 15 letters of vision from baseline, compared to 12.3% of patients receiving sham injections (p<0.0001). In the study, EYLEA® was generally well tolerated. The most common adverse events were those typically associated with intravitreal injections or the underlying disease. Serious ocular adverse events in the EYLEA® group were uncommon (3.5%), consisting of individual reports of corneal abrasion, endophalmitis, retinal vein occlusion, and reduced visual acuity, and were more frequent in the control group (13.5%). The incidence of non-ocular serious adverse events was generally well-balanced between the treatment arms. There were no deaths among the 114 patients treated with EYLEA® and two (2.7%) in the 73 patients treated with sham injections.
The one-year COPERNICUS results showed that 55.3% of patients receiving EYLEA® dosed monthly for 24 weeks, then on a PRN basis (guided by anatomic and visual acuity monitoring) over the next 28 weeks, gained at least 15 letters from baseline on an ETDRS eye chart compared to 30.1% of patients who received sham injections for the first 24 weeks followed by EYLEA® PRN from week 24 to week 52 (p=0.0006). In terms of gain in visual acuity from baseline to week 52, patients receiving EYLEA® monthly for 24 weeks followed by EYLEA® PRN gained, on average, 16.2 letters of vision compared to a mean gain of 3.8 letters for patients who switched at week 24 from sham to EYLEA® PRN (p<0.0001). These results demonstrate that the benefits achieved with monthly EYLEA® treatment through week 24 were maintained out to week 52. At week 24, patients receiving EYLEA® had a mean gain of 17.3 letters, while patients receiving sham had a mean loss of 4.0 letters (p<0.0001). Patients who received EYLEA® monthly followed by EYLEA® PRN, were administered a mean of 2.7 EYLEA® injections from week 24 to 52, while patients who switched from sham to EYLEA® PRN received a mean of 3.9 EYLEA® injections. EYLEA® was generally well tolerated in the study. At week 52, the most frequently reported adverse events in patients who went from monthly EYLEA® to EYLEA® PRN were reduction of visual acuity, conjunctival hemorrhage, eye pain, and intraocular pressure increased. The most frequently reported adverse events in patients who switched from sham to EYLEA® PRN were reduction of visual acuity, conjunctival hemorrhage, intraocular pressure increased, and retinal hemorrhage. At week 52, 5.3% of patients receiving EYLEA® who switched to EYLEA® PRN and 16.2% of patients who switched from sham to EYLEA® PRN reported at least one ocular serious adverse event.
In April 2011, we and Bayer HealthCare announced that in the GALILEO study, EYLEA® also demonstrated a statistically significant improvement in visual acuity at six months compared to sham injections, the primary endpoint of the study. In this trial, 60.2% of patients receiving 2.0 mg of EYLEA® monthly gained at least 15 letters of vision from baseline, compared to 22.1% of patients receiving sham injections (p<0.0001). Patients receiving 2.0 mg of EYLEA® monthly gained, on average, 18 letters of vision compared to a mean gain of 3.3 letters with sham injections (p<0.0001), a secondary endpoint.
As in the COPERNICUS trial, EYLEA® was generally well tolerated in the GALILEO study and the most common adverse events were those typically associated with intravitreal injections or the underlying disease. Serious ocular adverse events in the EYLEA® group were 2.9% and were more frequent in the control group (8.8%). The most frequently reported adverse events overall in the EYLEA® arm were eye pain, conjunctival hemorrhage, and elevated intraocular pressure. The most frequently reported adverse events in the control group were macular edema, eye irritation, and reduced visual acuity. The incidence of non-ocular serious adverse events was generally well-balanced between the treatment arms. The most frequent non-ocular adverse events were headache and nasopharyngitis. There were no deaths in the study.
The one-year GALILEO results showed that 60.2% of patients receiving EYLEA® dosed monthly for 24 weeks, then on a PRN basis (guided by anatomic and visual acuity monitoring) over the next 28 weeks, gained at least 15 letters from baseline on an ETDRS eye chart compared to 32.4% of patients receiving sham injections (p=0.0004). In terms of gain in visual acuity from baseline to week 52, patients receiving EYLEA® gained, on average, 16.9 letters of vision compared to a mean gain of 3.8 letters for patients receiving sham injections (p<0.0001). These results demonstrate that the benefits achieved with monthly EYLEA® treatment through week 24 were maintained out to week 52. At week 24, patients receiving EYLEA® had a mean gain of 18 letters compared to a mean gain of 3.3 letters for patients with sham injections (p<0.0001). Patients treated with EYLEA® received an average of 2.5 EYLEA® injections from week 24 to week 52. EYLEA® was generally well tolerated in the study. At week 52, the most frequently reported adverse events overall in the EYLEA® arm were macular edema, elevated intraocular pressure, eye pain, conjunctival hemorrhage, and retinal hemorrhage. The most frequently reported adverse events in the sham group were macular edema, retinal hemorrhage, retinal vascular disorder, reduction of visual acuity and eye irritation. At week 52, 9.6% of patients in the EYLEA® arm and 8.8% of patients in the sham arm presented with at least one ocular serious adverse event.
Based on the positive six-month results in the COPERNICUS and GALILEO studies , we submitted a supplemental BLA for U.S. regulatory approval of EYLEA® in CRVO in November 2011. Under the Prescription Drug User Fee Act (PDUFA), we were granted a target date for an FDA decision on our EYLEA® supplemental BLA of September 23, 2012. Bayer HealthCare plans to submit regulatory applications in this indication in Europe in late 2012 or early 2013.
In the second quarter of 2011, we and Bayer HealthCare initiated Phase 3 studies to evaluate the safety and efficacy of EYLEA® in DME. These clinical trials have three study arms. In the first arm, patients will be treated every month with 2.0 mg of EYLEA® . In the second arm, patients will be treated with 2.0 mg of EYLEA® every two months after an initial phase of monthly injections. In the third arm, the comparator arm, patients will be treated with macular laser photocoagulation. The primary endpoint of the study is mean change in visual acuity from baseline as measured by the ETDRS eye chart. All patients will be followed for three years. We are conducting one of these studies, called VISTA-DME ( V EGF Trap-Eye: I nvestigation of S afety, T reatment effect, and A natomic outcomes in DME ), with study centers in the United States. Bayer HealthCare is conducting the second study, named VIVID-DME ( V EGF Trap-Eye I n V ision I mpairment D ue to DME ), with study centers in Europe, Japan, and Australia. The VISTA-DME trial was fully enrolled in early 2012.
In the first quarter of 2011, we and Bayer HealthCare initiated a Phase 3 trial in Asia in collaboration with the Singapore Eye Research Institute (SERI) investigating the efficacy and safety of EYLEA® in patients with CNV of the retina as a result of pathologic myopia. The study, which will enroll approximately 110 patients, has started in Japan and is scheduled to run until June 2013.
In the first quarter of 2012, we plan to initiate a multinational study of EYLEA® in patients with BRVO (VIBRANT).
Collaboration with Bayer HealthCare
In October 2006, we entered into a license and collaboration agreement with Bayer HealthCare for the global development and commercialization outside the United States of EYLEA® . Under the agreement, we and Bayer HealthCare collaborate on, and share the costs of, the development of EYLEA® through an integrated global plan. Bayer HealthCare will market EYLEA® outside the United States, where the companies will share equally in profits from any future sales of EYLEA® . Commencing on the first commercial sale of EYLEA® in a major market country outside the United States, we will be obligated to reimburse Bayer HealthCare for 50% of the development costs that it has incurred under the agreement from our share of the collaboration profits. The reimbursement payment in any quarter will equal 5% of the then outstanding repayment obligation, but never more than our share of the collaboration profits in the quarter unless we elect to reimburse Bayer HealthCare at a faster rate. Within the United States, we retain exclusive commercialization rights to EYLEA® and are entitled to all profits from any such sales. We have received $60 million in development milestone payments and can earn up to $50 million in future milestone payments related to marketing approvals of EYLEA® in major market countries outside the United States. We can also earn up to $135 million in sales milestone payments if total annual sales of EYLEA® outside the United States achieve certain specified levels starting at $200 million.
Competition
EYLEA® . The market for eye disease products is very competitive. Novartis and Genentech are collaborating on the commercialization and further development of a VEGF antibody fragment (Lucentis® ) for the treatment of wet AMD, DME, RVO, and other eye indications. Lucentis® was approved by the FDA in June 2006 for the treatment of wet AMD and in June 2010 for the treatment of macular edema following retinal vein occlusion (RVO). Lucentis® was approved by the European Medicines Agency (EMA) for wet AMD in January 2007, for the treatment of DME in January 2011, and for the treatment of RVO in June 2011. Many other companies, including Genentech, are working on the development of product candidates and extended delivery devices for the potential treatment of wet AMD, DME, and RVO including those that act by blocking VEGF and VEGF receptors, as well as use of small interfering ribonucleic acids (siRNAs) that modulate gene expression. For example, in January, 2012, Genentech submitted an IND for an extended delivery device. In addition, ophthalmologists are using off-label, with success for the treatment of wet AMD, DME, and RVO, a third-party repackaged version of Genentech’s approved VEGF antagonist, Avastin® (bevacizumab). The relatively low cost of therapy with Avastin® in patients with wet AMD presents a significant competitive challenge in this indication. The National Eye Institute (NEI) and others are conducting long-term, controlled clinical trials comparing Lucentis® to Avastin® in the treatment of wet AMD. One-year data from the Comparison of Age-Related Macular Degeneration Treatments Trial (CATT) were reported in April 2011 and indicated that Avastin® dosed monthly was non-inferior to Lucentis® dosed monthly in the primary efficacy endpoint of mean visual acuity gain at 52 weeks. Avastin® is also being evaluated in eye diseases in trials that have been initiated in the United Kingdom, Canada, Brazil, Mexico, Germany, Israel, and other areas. It may be difficult for EYLEA® to compete in this or other eye indications for which it may be approved against Lucentis® and off-label use of Avastin® because doctors and patients have had significant experience using these medicines and because of the relatively low cost of Avastin® . Moreover, the recently reported results of the CATT study, combined with the relatively low cost of Avastin® in treating patients with wet AMD, may well exacerbate the competitive challenge which EYLEA® will face in this or other eye indications for which it may be approved. In addition, while we believe that ZALTRAP® would not be well tolerated if administered directly to the eye, if ZALTRAP® is approved for the treatment of certain cancers, there is a risk that third parties will attempt to repackage ZALTRAP® for off-label use and sale for the treatment of wet AMD and other diseases of the eye, which would present a potential low-cost competitive threat to EYLEA® for wet AMD or other eye indications.
●ZALTRAP® (aflibercept) also known as VEGF Trap kｿ Oncology 【2011】 ZALTRAP® (aflibercept) is a fusion protein that is designed to bind all forms of VEGF-A, VEGF-B, and PlGF, and prevent their interaction with cell surface receptors. VEGF-A (and to a lesser degree, PlGF) is required for the growth of new blood vessels (a process known as angiogenesis) that are needed for tumors to grow.
ZALTRAP® is being developed globally in cancer indications in collaboration with Sanofi. In April 2011, we and Sanofi announced that the Phase 3 VELOUR trial evaluating ZALTRAP® in combination with the FOLFIRI chemotherapy regimen [folinic acid (leucovorin), 5-fluorouracil, and irinotecan] versus a regimen of FOLFIRI plus placebo met its primary endpoint of improving overall survival (OS) in previously treated metastatic colorectal cancer (mCRC) patients. The VELOUR data were presented in June 2011 at the European Society of Medical Oncology World Congress on Gastrointestinal Cancer. In this study, the addition of ZALTRAP® to the FOLFIRI chemotherapy regimen significantly improved both overall survival (HR=0.817; p=0.0032) and progression-free survival (HR=0.758; p=0.00007) compared to FOLFIRI plus placebo. A similar effect was seen with ZALTRAP® therapy whether or not patients had received prior bevacizumab therapy.
In the VELOUR study, grade 3 or 4 adverse events that occurred with a more than two percent greater incidence in the ZALTRAP® arm than in the placebo arm included diarrhea, asthenia/fatigue, stomatitis/ulceration, infections, hypertension, GI/abdominal pains, neutropenia, neutropenic complications and proteinuria. Deaths on study treatment due to adverse events occurred in 2.4 percent of patients in the ZALTRAP® arm and in 1.0 percent of patients in the placebo arm.
Based upon these positive findings, Sanofi submitted regulatory applications for marketing approval of ZALTRAP® for the treatment of previously-treated mCRC patients to the European Medicines Agency (EMA) in December 2011, and to the FDA in early February 2012.
Another randomized, double-blind Phase 3 trial (VENICE), which is fully enrolled, is evaluating ZALTRAP® as a first-line treatment for hormone-refractory metastatic prostate cancer in combination with docetaxel/prednisone. The VENICE trial is being monitored by an Independent Data Monitoring Committee (IDMC), a body of independent clinical and statistical experts. The IDMCs meet periodically to evaluate data from the trial and may recommend changes in study design or study discontinuation. In July 2011, the study’s IDMC met for a scheduled interim analysis and recommended that the trial continue to completion. A final analysis will be conducted when a pre-specified number of events have occurred in this trial, which is anticipated in the second quarter of 2012.
In December 2011, we announced initial data from the Phase 2 AFFIRM study in the first-line mCRC setting of ZALTRAP® in combination with the modified FOLFOX6 [folinic acid (leucovorin), 5-fluorouracil, and oxaliplatin] chemotherapy regimen. The primary endpoint of the study was the Progression Free Survival (PFS) rate at one year. The results showed that in patients who received ZALTRAP® , the PFS rate at one year was similar to that seen in the standard therapy arm for patients who received modified FOLFOX6 alone. The study was not designed for a direct statistical comparison between arms. The control arm was used as an internal benchmark only. The side effect profile of ZALTRAP® was similar to what has been seen in prior trials with ZALTRAP® .
ZALTRAP® Collaboration with Sanofi
We and Sanofi globally collaborate on the development and commercialization of ZALTRAP® . Under the terms of our September 2003 collaboration agreement, as amended, we and Sanofi will share co-promotion rights and profits on sales, if any, of ZALTRAP® outside of Japan for disease indications included in our collaboration. In Japan, we are entitled to a royalty of approximately 35% on annual sales of ZALTRAP® , subject to certain potential adjustments. We may also receive up to $400 million in milestone payments upon receipt of specified marketing approvals, including up to $360 million related to the receipt of marketing approvals for up to eight ZALTRAP® oncology and other indications in the United States or the European Union and up to $40 million related to the receipt of marketing approvals for up to five oncology indications in Japan.
Under the ZALTRAP® collaboration agreement, as amended, agreed upon worldwide development expenses incurred by both companies during the term of the agreement will be funded by Sanofi. If the collaboration becomes profitable, we will be obligated to reimburse Sanofi out of our share of ZALTRAP® profits for 50% of the development expenses that they funded. The reimbursement payment in any quarter will equal 5% of the then outstanding repayment obligation, but never more than our share of the ZALTRAP® profits in the quarter unless we elect to reimburse Sanofi at a faster rate.
Competition
ZALTRAP® . Many companies are developing therapeutic molecules designed to block the actions of VEGF specifically and angiogenesis in general. A variety of approaches have been employed, including antibodies to VEGF, antibodies to the VEGF receptor, small molecule antagonists to the VEGF receptor tyrosine kinase, and other anti-angiogenesis strategies. Many of these alternative approaches may offer competitive advantages to aflibercept in efficacy, side-effect profile, durability of effect, or method of delivery. Additionally, some of these molecules are already approved for marketing and have a broader range of indications than our product candidate.
In particular, Genentech has an approved VEGF antagonist, Avastin® , on the market for treating certain cancers and a number of pharmaceutical and biotechnology companies are working to develop competing VEGF antagonists, including Novartis, Amgen, Imclone LLC/Eli Lilly, Pfizer, AstraZeneca, and GlaxoSmithKline. Many of these molecules are further along in development than ZALTRAP® and may offer competitive advantages over our molecule. Pfizer, Onyx (together with its partner Bayer HealthCare), and GlaxoSmithKline are selling and marketing oral medications that target tumor cell growth and new vasculature formation that fuels the growth of tumors.
Monoclonal Antibodies. Our clinical candidates in development are all fully human monoclonal antibodies which were generated using our VelocImmune® technology. Our antibody generation technologies and clinical candidates face competition from many pharmaceutical and biotechnology companies using various technologies.
Numerous other companies are developing therapeutic antibody products. Companies such as Pfizer, Johnson & Johnson, AstraZeneca, Amgen, Biogen Idec, Inc., Novartis, Genentech, Bristol-Myers Squib, Abbott, and GlaxoSmithKline have generated therapeutic products that are currently in development or on the market that are derived from recombinant DNA that comprise human antibody sequences. As noted above, Astellas has licensed our VelocImmune® technology as part of their internal antibody development programs.
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●Regeneron Pharmaceuticals, Inc.[US] ●PRODUCTS ●Pipeline ●Science ■Investors ●Press Releases ●SEC Filings 10-K annual report[21-Feb-2012] - [pdf] - [xls]
■Repros Therapeutics Inc.[US]
- http://www.reprosrx.com/ 2006.5 Zonagen Inc.からRepros Therapeutics Inc.に社名変更(Nasdaq: RPRX) ●会社決算
($ 000) 2007 2006 2005 2004 2003 2002 2001 ライセンス収入 - - - - - 研究開発グラント - - 4 118 595 利子収入 1,508 596 630 104 318 資産からの収入 - - - - 102 他の収入 - - - 35 - 売上高 合計 1,508 596 634 257 1,015 当期純利益 (13,700) (14,195) (7,391) (3,697) (3,329) 研究開発費 12,420 11,912 6,101 2,471 2,161 従業員数[連結] 7
●Repros Therapeutics Inc.[US] ●Product Pipeline ★Proellex(R) 慢性uterine fibroids(子宮筋腫) P3/子宮筋腫に伴う貧血P3/子宮内膜症P2 (an orally active, small molecule, selective blocker of the progesterone receptor) ★Androxal(R) (a single isomer of clomiphene citrate and an orally active small molecule ) Idiopathic hypogonadotropic hypogonadism (IHH)特発性低ゴナドトロピン性性腺機能低下症 P2b Secondary Hypogonadism with Male Fertility Maintenance & Improvement P2 Hypogonadism Associated with Metabolic Syndrome/ Secondary Hypogonadism and AIHH P2 ■Investors & Media ●SEC Filings ★10-K Annual report[2008.3.17] ●News
■Roche AG
●主要系列会社 Genentech [2008末持株比率55.8%] 中外製薬 [2008末持株比率61.5%] ●Boehringer Mannheim Roche acquires Boehringer Mannheim Group[1997.5.26] - 1997.5.24 RocheはB-M社の単独株主Corange Ltdから全株を買収。 ●会社決算From Financial data[xls] 註) 欧米企業は前年の数値を比較する時に、成績を強調するため実際の決算数値 ではなく継続事業[Continuing business]のみの数値を参照することが多い。 Rocheの場合これを多用するが、上記数値は決算値。 ●個別製品売上高
(CHF milllion) 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 売上高 49,051(+) 45,617(-1) 46,133(+10) 42,041(+18) 35,511 31,273 31,220 29,453 29,163 28,672 EBITDA 15,012 16,637 17,068 14,436(+25) 11,404 9,566 8,609 6,032 6,438 11,126 営業利益 12,277 13,896 14,468(+23) 11,730(+28) 8,669 8,979 5,592 1,335 3,247 7,131 純利益 8,510 10,844(-5) 11,437(+25) 9,171(+34) 6,866
旧5,7876,641 3,069 (4,026) 3,697 8,647 研究開発費 9,874 8,845 8,385(+14) 6,589 5,705 5,093 4,766 4,257 3,893 3,950 うち医薬 8,896(+13) 7,904(+4) 7,598(+15) 従業員数[年度末] 80,080 78,604 74,372 68,218 64,703 65,357 69,659 63,717 64,758 ■事業別売上高 Pharmaceuticals 38,996(+8) 35,961 36,783(+10) 33,294(+22) 27,268 21,695 19,781 17,294 17,062 15,992 うちRoche 22,164 22,970(+11) 20,666(+22) 16,955 13,970 13,243 Genentech 10,461 10,414(+14) 9,125(+38) 6,614 4,522 3,382 Chugai 3,336 3,399(-3) 3,503(-5) 3,699 3,203 3,156 Diagnostics 10,055 9,656(+3) 9,350(+7) 8,747 8,243 7,827 7,409 7,194 6,900 6,252 Consumer Health (OTC) - - - - - 1,751 1,770 1,578 1,661 1,694 Vitamins等精密化学 - - - - - 2,260 3,387 3,540 3,571 Fragrances and Flavours - - - - - - - - - 1,163 ■地域別売上高 Switzerland 509 489 472 501 442 529 529 513 509 European Union 15,601 15,,465 13,627 11,570 10,563 9,681 9,011 9,000 9,012 Rest of Europe 1,521 1,620 1,503 1,206 993 1,520 1,439 1,282 1,266 Europe 計 17,631 17,574 15,601 13,277 11,998 11,730 10,979 10,795 10,787 米国 16,362 17,069 15,685 12,667 10,430 他の北米 932 1,004 985 812 595 North America計 17,294 18,073 16,670 13,479 11,025 10,789 11,102 11,264 10,636 Latin America 2,975 2,784 2,539 2,033 1,825 2,076 2,376 2,827 2,928 Japan 3,532 3,562 3,713 3,948 3,875 3,948 2,243 1,589 1,580 Rest of Asia 2,920 2,681 2,384 1,803 1,553 1,697 1,804 1,829 1,814 Asia 計 6,452 6,243 6,097 5,751 5,428 5,645 4,047 3,418 3,394 Africa,豪州・太平洋 1,265 1,,459 1,134 971 997 980 949 859 927 ■[医薬]薬効別売上高 腫瘍 19,210(+2)[59%] 21,252[57%] 19,654(+15)[55%] ウイルス 2,663(-16)[8%] 3,543[10%] 3,408(-27)[9%] 炎症・自己免疫・移植 2,816(+7)[9%] 2,950[8%] 3,264(+19)[9%] 代謝・骨 2,015(-12)[6%] 2,568[7%] 2,839(+7)[8%] 眼科薬 1,523(+23)[5%] 1,458[4%] 呼吸器官薬 1,095(+10)[3%] 1,154[3%] 腎貧血 1,018(-9)[3%] 1,207[3%] 1,318(-11)[4%] 循環器系薬 901(+4) 962 神経系薬 851(-2) 966 感染症 355(-7) 422 その他 347(-31) 556 5,478(-5)[5%] 医薬 計 32,794(+0) 37,058 35,961(+5)[100%] ■換算レート(年度末) 1 USD 1.06SFr 1.13SFr 1 Eur 1.49SFr 1.66SFr 100 JPY 1.17SFr 1.00SFr 1) Roche and Genentech combined 2) Marketed by Chugai. 3) Jointly marketed by Genentech and Novartis.
(CHF milllion) 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 備考 ★癌 Mabthera/Rituxan 1) 5,027(+7)
978(+19)5,363
9936,087(+6) 5,923(+16) 5,516(+15) 4,839(+15) 4,154(+22) 3,378(+28) 2,775(+34) 2,332(+48) 1,695(+90) 900(84%) ??? rituximab(リンパ腫)米・日を除く全世界 米国 2,722(+6) 3,026 3,015(+3) 西欧 1,574(+7) 1,639 1,643(+10) 日本 254(-1) 273 244(+3) 国際 1,455(+14) 1,418 1,185(+8) Avastin 5,292(-7) 6,461 6,222(+21) 5,207(+37) 4,106(+41) 2,962(+76) 1,665(+141) 690 - - - - - bevacizumab(大腸癌)米国を除く全世界 米国 2,343(-14) 3,190 3,315(+14) 西欧 1,448 1,762 1,790(+24) 日本 627 625 404(+74) 国際 874 884 713(+35) Herceptin 1) 5,253(+9) 5,429 5,266(+8) 5,092(+12) 4,852(+23) 3,927(+81) 2,146(+48) 1,435(+26) 1,177(+27) 1,007(+33) 806(+52) 540(77%) ??? trastuzumab(乳がん)米国を除く全世界 米国 1,422 1,591 1,566(+4) 西欧 1,941 2,075 2,125(+2) 日本 288 300 345(+25) 国際 1,602 1,463 1,230(+18) Tarceva 1,251(+7) 1,325 1,304(+10) 1,215(+23) 1,062(+31) 813(+108) 387(+2,224) - - - - - - erlotinib[肺癌、膵臓癌] 米国 484 523 521(+5) 西欧 370 432 475(+11) 日本 92 94 67(+28) 国際 305 276 241(+18) Xeloda 1,354(+6) 1,426 1,260(+7) 1,211(+13) 1,151(+19) 971(+20) 796(+47) 534(+7) 515(+29) 444(+82) 260(+74) --- ??? capecitabine(乳がん)(大腸癌) 米国 517 5360 473(+10) 西欧 264 305 311(-3) 日本 112 128 77(+40) 国際 461 463 399(+9) Neutrogin 2) 278(-10) 331 - 404(-3) 405(+13) 379(+9) 364(+15) 322(+2) 318(+265) - - - - lenograstim[化学療法に伴うneutropenia] Furtulon - - - - - - ? 248(-9) 303(0) 340(23%) 280 doxifluridine(主に大腸癌,ほかに乳癌胃癌) Kytril - - 425(-12) 498(+0) 500(+9) 457(+8) 437(+7) 451(+12) 437(-) [GSK] GSK granisetrone(化学療法・放射線によるめまい・吐気) Neupogen - - - - - - ? ? 316(+6) 300(19%) 250 filgrastim [neutropeniaによる感染抑制] ★ウイルス Pegasys 1,438(-3) 1,645 1,655(+5) 1,635(+6) 1,637(+11) 1,467(+3) 1,403(+17) - - - - - - peginterferon alfa-2a[B,C型肝炎] 米国 343 389 404(+2) 西欧 297 352 398(-2) 日本 93 124 129(+14) 国際 705 780 724(+8) Pegasys + Copegus - - - - - 1,562(+72) 942(+1010) - - - - peginterferon alfa-2a + ribavirin(C肝炎) Copegus 164(-14) 212 - - - - 407(+6) - - - - - - ribavirin(C型肝炎) Tamiflu 359(-53) 873 3,200(+435) 609(-68) 2,085(-19) 2,627(+68) 1,558(+370) 330(-22) 431(+184) - - - - oseltamivir(インフルエンザA,B) 米国 160 243 906(+110) 西欧 53 2 784(+5080) 日本 97 216 884(+808) 国際 49 412 626(+829) Cymevene/Valcyte 569(+7) 605 - 553(+10) 542(+12) 488(+22) 394(+19) 329(+22) 281(+6) 296(+8) 292(+28) --- 210 valganciclovir [CMV,HIV] Roferon-A - - - - - - ? ? ??? 260(-9%) 280 IFN-α-2a [B,C肝炎] Viracept - - - - - - 276(-12) 320(-26) 452(-8) 500(15%) 430 nelfinavir [HIV] Fortovase/Invirase - - - - - - ? ? ??? 280(-20%) 350 saquinavir [HIV] ★炎症・自己免疫・移植－拒絶反応抑制 CellCept 991(-14) 1,290 1,576(-22) 2,099(+13) 2,012(+10) 1,842(+7) 1,705(+20) 1,403(+10) 1,335(+27) 1,173(+18) 1,056(+36) 790(40%) 560 [mycophenolate moxetil]拒絶反応抑制 米国 203 275 549(-47) 西欧 284 451 494(+1) 日本 64 61 51(+12) 国際 440 503 482(+0) ★腎・貧血 NeoRecormon,Epogin 222(-22)
674(-22)333
9521,560(-11) 1,774(-13) 2,094(-7) 2,227(-1) 2,252(+8) 2,082(+1) 2,051(+77) 1,192(+67) 746(+19) 650(34%) 480 epoetin beta(貧血) 米国 - - - 西欧 310 474 679(-19) 日本 320 476 515(-1) 国際 266 335 366(-5) Mircera 344(+50) 255 ★代謝疾患・骨 Bonviva/Boniva 696(-22) 1,013 - 1,108(+35) 887(+85) 488(+462) ibandronic acid [骨粗鬆症] Xenical 238(-21) 337 - 502(-13) 632(-10) 693(+7) 635(+5) 593(-2) 618(-13) 763(+16) 963(+4) 950(1) 940 orlistat [肥満症] Rocaltrol - - - - - - ? ? 242(-8) 280(13%) 250 calcitriol [骨粗鬆症] Nutropin/Protropin 1) 317(-8) 405 - 413(-2) 470(-1) 494(+3) 476(+6) 448(+9) 442(+8) 477(+19) 435(+11) 390(16%) ??? somatropin/somatrem 成長ホルモン Evista 206(-1) 222 [raloxifene] ★循環器 Activase/TNKase 1) 453(+15) 460 - 342(-1) 382(+9) 362(+15) 310(+11) 275(+6) 278(+1) 322(-6) 371(-5) 330(-16%) ??? alteplase 心筋梗塞 Dilatrend - - - - 326(-11) 361(-8) 392(+19) 329(+18) 289(+23) 240(36%) ??? carvedilol 心不全、高血圧、冠動脈疾患 Inhibase - - - - - - ? 223(-2) cilazapril(降圧剤) Torem - - - - - - ? 216(-4) torasemide(降圧剤) ★呼吸器 Pulmozyme 1) 492(+10) 513 - 496(+12) 483(+12) 436(+10) 393(+15) 338(+8) 328(+14) 320(+7) 319(+7) 300(15%) ??? dornase alpha /DNase [Cystic fibrosis膵嚢胞性線維症] Xolair 3) 603(+11) 641 560(+10) 567(+10) 537(+31) 408(+74) - - - - - - omalizumab[喘息] ★神経系 Madopar 294(+6) 308 - 311(+4) - - - 245(+2) 241(+4) 239(+2) 246(+4) 250(4%) 240 levodopa+benserazide[抗parkinson] Lexotan - - - - - - 214(-9) 244(-6) 274(-3) 290(2%) 280 bromazepam(抗不安剤) Dormicum/Versed - - - - - - ? ? ??? 470(-45%) 840 midazolam (催眠、麻酔) Rivotril 187(-3) 218 [clonazepan] RoActemra 618(+73) 397 146(+289) [tocilizumab]関節リウマチ;EU承認2009.1 日本 195 167 98(+146) ★眼科 Lucentis 3) 1,523(+23) 1,458 1,198(+24) 960(+7) 991(+117) 478(-) ranibizumab [黄斑変性AGMD] 米国 1,523 1,458 1,198(+24) 西欧 - 日本 - 国際 - ★感染症 Rocephin 265(-6) 311 - 344(-10) 399(-4) 416(-56) 927(-29) 1,302(0) 1,375(0) 1,548(-2) 1,698(+1) 1,710(-3%) 1,760 ceftriaxone ★皮膚 Roaccutane/Accutane - - - - - 316(-37) 515(-17) 911(-16) 1,166(-8) 1,280(23) 1,040 isotretinoin(重症ざ瘡Acne) 上位２０製品 30,758(+8)[86%] その他 5,203(-12)[14%] 医薬品 計 32794 37058 35,961(+5)[100%] 米国 西欧 日本 国際
●Herceptin(trastuzumab) 乳癌 【2008】
Growth continued to be driven by increasing adoption in adjuvant (early stage) HER2-positive breast cancer. Roche estimates that by the end of 2008 the product’s market share in the adjuvant setting was approximately 75% (versus 70% a year earlier) in the five largest European markets. Elsewhere, market penetration in this setting also continues to build. In the US penetration into this market flattened during 2008 due to earlier, more rapid adoption of Herceptin for adjuvant treatment. In the metastatic setting, adoption rates and treatment duration remained stable both in the US and in the top five European markets.【2007】
Sales of Herceptin (trastuzumab), which is designed to treat a particularly aggressive form of tumour (HER2-positive) that accounts for 20.30% of all breast cancers, continued to deliver strong growth throughout the year. This performance was primarily driven by growth in the adjuvant (earlystage) breast cancer segment in Germany, France, Italy, Spain and the United Kingdom, the top five European markets. Due to earlier, rapid adoption of Herceptin for adjuvant treatment, the product’s market penetration in the United States stabilised at a high level during 2007. In the metastatic setting, adoption rates and treatment duration remained stable both in the US and in the top five European markets. New data from the NeoAdjuvant Herceptin (NOAH) study released in June show that treatment with Herceptin to reduce tumour size before surgery helps eradicate HER2- positive tumours and may reduce the need for breast removal. These results add to the substantial evidence supporting Herceptin as the foundation of care for women with HER2-positive breast cancer at all stages of the disease. In May Roche gained EU approval for the use of Herceptin in combination with hormonal therapy (aromatase inhibitor) for the treatment of patients with metastatic breast cancer that is both HER2-positive and hormone receptor-positive.●MabThera/Rituxan (rituximab) 非ホジキンリンパ腫 【2008】
Double-digit sales growth was driven by increasing use in oncology indications and rheumatoid arthritis. In Europe and the US most of the oncology sales growth was due to increasing usage of MabThera/Rituxan following first-line therapy of indolent non-Hodgkin's lymphoma (NHL), including maintenance use. The already high penetration rates for first-line treatment of indolent and aggressive NHL were sustained in the US and Europe’s five largest markets (France, Germany, Italy, Spain and the United Kingdom), while increasing adoption in these settings was seen in emerging markets. Adoption in rheumatoid arthritis (RA) continued to increase in both the US and Europe/Rest of World (RoW). An estimated 800 million Swiss francs of sales were generated in the RA indication.【2007】
MabThera/Rituxan (rituximab), for the treatment of patients with non-Hodgkin's lymphoma (NHL), maintained strong sales growth throughout 2007. Increases were driven by the use of MabThera for maintenance treatment in follicular lymphoma, the most common form of indolent lymphoma, as well as first-line treatment for indolent forms of the disease in all markets, particularly in Europe/ Rest of World (RoW). This growth was supported by strong uptake of first-line treatment of patients with aggressive NHL in emerging markets. In January 2008 the European Commission approved an application filed by Roche last July to extend the product’s existing first-line indolent lymphoma indication to include the use of MabThera with any chemotherapy combination. The expanded indication makes treatment with MabThera available to a wider group of patients across Europe.【2007～リウマチ】
Adoption by physicians of MabThera/Rituxan, the first and only selective B cell therapy for the treatment of rheumatoid arthritis (RA) in patients who have an inadequate response to or can not tolerate TNF inhibitors, continued to increase throughout 2007. The product has now been launched in the major European markets, North and Latin America, and other markets worldwide. Data published in May show that, in patients whose RA had not responded adequately to TNF inhibitor therapy, treatment with MabThera controlled disease activity more effectively than switching to an alternative TNF inhibitor. In February new data were added to the European prescribing information on the ability of MabThera to significantly slow progression of joint damage in patients with inadequate response or intolerance to TNF inhibitor therapy. In August MabThera was recommended by the National Institute for Clinical Excellence (NICE) in England and Wales, making it the first and only therapy recommended by the Institute for patients with an inadequate response to at least one TNF inhibitor.●Avastin (bevacizumab), 【2008】
Sales increased 37% worldwide compared to 2007, with strong growth in all regions, particularly Europe/RoW (+67%). In the US growth was driven primarily by increased usage in metastatic breast cancer following accelerated approval by the US Food and Drug Administration (FDA) in February. Sales growth in Europe was driven primarily by increased use of the medicine for metastatic colorectal and breast cancer.
Sales in Europe also benefited from the rollout of new indications and increasing uptake for non-small cell lung cancer and renal cell carcinoma.【2007】
Avastin (bevacizumab), the first antiangiogenic therapy to demonstrate overall and/or progressionfree survival benefits in patients with colorectal, lung, breast and kidney cancer, continued to record strong sales growth in all regions. Sales growth in the United States was driven primarily by increased use in advanced non-small cell lung cancer (NSCLC). In Europe sales growth was boosted by further uptake of the product in the metastatic colorectal cancer setting. In March the European authorities approved Avastin for the treatment of metastatic breast cancer in combination with chemotherapy (paclitaxel). The approval is based on clinical trial data showing that patients have the chance to live twice as long without their cancer progressing if treated with Avastin plus paclitaxel, compared with paclitaxel alone. Avastin was approved in April in Japan for advanced or recurrent colorectal cancer and in August in Europe, in combination with platinum-based chemotherapy, for the treatment of advanced NSCLC. Avastin is the first medicine to prolong the life of NSCLC patients beyond one year. In December the EU authorities approved Avastin in combination with interferon for the treatment of advanced renal cell carcinoma, the most common form of kidney cancer. Also in December the EU’s Committee forMedicinal Products for Human Use (CHMP) recommended widening the product’s existing marketing authorisation in advanced colorectal cancer to allow it to be combined with any chemotherapy in any line of therapy; subject to final approval by the European Commission, the updated marketing approval will offer patients a significantly greater range of treatment options.In August Genentech resubmitted its supplemental marketing application to the US Food and Drug Administration (FDA) for use of Avastin in combination with paclitaxel as first-line treatment of patients with locally recurrent or metastatic breast cancer. In December the agency’s Oncologic Drugs Advisory Committee voted five to four that the data are not sufficient to establish a favourable risk/ benefit analysis for Avastin in this setting. Genentech will continue to work with the FDA to make Avastin available for US breast cancer patients. The FDA is expected to make a decision on the application by 23 February 2008.
【2007～開発】
The ongoing clinical development programme for Avastin is expected to include over 40,000 patients worldwide. In addition to further trials with the aim of broadening the product’s use in breast and lung cancer, Avastin is also being studied in potential new indications, including prostate, ovarian, gastric and brain (glioblastoma) cancers, as well in aggressive non-Hodgkin’s lymphoma (in combination with MabThera/Rituxan). Major phase III trials are currently also investigating Avastin in the adjuvant setting in colon, lung and HER2-negative breast cancer.A phase III trial of the medicine in HER2-positive adjuvant breast cancer is scheduled to begin in 2008.●Xeloda (capecitabine), 【2008】
Xeloda recorded sustained double-digit sales growth throughout 2008. Growth in Japan was particularly strong at 74%, and solid increases were also recorded in the US (+9%) and Europe/RoW (+14%). Sales were driven by expanded indications approved in 2007 and 2008, notably stomach cancer and advanced colorectal cancer, along with uptake in breast cancer.【2007】
Xeloda (capecitabine), an oral anticancer medicine that greatly simplifies treatment, recorded doubledigit sales growth in 2007, with the main contributions coming from the US (+19%) and Europe/ RoW (+19%). Sales were boosted by EU approval of Xeloda for the treatment of advanced gastric (stomach) cancer and by positive data on its use in colorectal cancer. In December the CHMP recommended approval of an application filed by Roche in April to broaden the product’s EU marketing authorisation to allow Xeloda to be used in any therapeutic combination in any line of metastatic (advanced) colorectal cancer treatment, including combinations with Avastin. The FDA is currently reviewing Roche’s application for US approval of Xeloda in combination with oxaliplatin, with or without Avastin, for first-line treatment and in combination with oxaliplatin for second-line treatment of metastatic colorectal cancer. In December Chugai received approval in Japan for Xeloda as therapy for adjuvant (post-surgery) colon cancer. Five-year follow-up data from the X-ACT trial presented at the European Cancer Conference (ECCO) in September show that patients with advanced colon cancer whose disease has progressed live longer when taking Xeloda compared with intravenous 5-fluorouracil plus folinic acid, the current standard treatment. In addition, data from a major trial in breast cancer published in December show that Xeloda in combination with Herceptin and docetaxel extended survival in HER2-positive patients by a further five months.●Tarceva (erlotinib) 【2008】
Tarceva recorded strong growth in 2008 (+23%), particularly in the Europe/RoW sales region (+27%), which now accounts for 55% of overall sales. US sales increased by 10% in a competitive market environment. Tarceva is still the only epidermal growth factor receptor inhibitor with a proven survival benefit in advanced lung and pancreatic cancer.【2007】
Tarceva (erlotinib), a targeted drug with proven survival benefit in advanced non-small cell lung cancer (NSCLC) and advanced pancreatic cancer, grew strongly over the previous year, mainly thanks to increased uptake in NSCLC and launches in additional countries. Tarceva was launched in China early in 2007, and in December Chugai launched the product in Japan for the second- and third-line treatment of NSCLC. Tarceva is now approved in 87 countries worldwide for the second- and third-line treatment of patients with advanced NSCLC. The EU launch in pancreatic cancer also contributed to Tarceva’s strong performance.
Tarceva is currently approved in more than 60 countries for patients with this difficult to treat disease, with further approvals anticipated in 2008.【2007～開発】
Tarceva is currently being evaluated in an extensive clinical development programme by a global alliance comprising OSI Pharmaceuticals, Genentech, Chugai and Roche. The programme of almost 20 clinical studies is investigating the benefits of Tarceva in lung cancer (including early-stage NSCLC) and other solid tumours.●EPO (NeoRecormon/Epogin) 【2008】
Combined sales of Roche's NeoRecormon and Chugai's Epogin (epoetin beta) were down 13% in a market that remains highly competitive due to pricing pressure from branded competitors and the entry of biosimilar versions of epoetin alfa in Europe. The market share of NeoRecormon has decreased only slightly, with global sales down 10% in 2008. In Japan, where Epogin remains the market leader, a decline in sales of 18% for the medicine was due primarily to sustained pricing pressure.【2007】
Combined sales of the erythropoietin-stimulating agents (ESAs) NeoRecormon and Epogin (epoetin beta) from Roche and Chugai, respectively, declined in a market that remains highly competitive due to pricing pressure from branded competitors and the entry of biosimilar versions of epoetin alfa in Europe. While the decline in NeoRecormon sales was slight, sales of Epogin in Japan were affected by competitive pricing pressures and, in the first quarter, the residual impact of government-mandated price cuts and reimbursement changes.●CellCept 【2008】
The immunosuppressant CellCept continued to record double digit sales growth worldwide (+13%), driven by solid demand in both the US and Europe. Growth continues to be driven by physicians' recognition of the long-term protective benefits of CellCept in transplant patients compared with other,more toxic therapeutic options.●Pegasys 【2008】
In 2008 Pegasys maintained its clear leadership of the global pegylated interferon market and continued to gain market share. Global sales increased 6% to 1.6 billion Swiss francs, driven by strong growth in Japan of 54% and growth in key emerging markets. This was combined with solid growth in the United States, where Pegasys now accounts for 70% of new prescriptions for hepatitis C.●Bonviva/Boniva 【2008】
In a highly competitive market, sales of Bonviva/Boniva (ibandronic acid) for the treatment of postmenopausal osteoporosis, increased by 221 million Swiss francs to 1.1 billion Swiss francs compared with 2007. The majority of sales come from the US, where the product’s market share remained robust despite the entry of generic versions of competitor products. Bonviva gained reimbursement status and was launched in many European markets in 2006.●Lucentis 【2008】
Sales of Lucentis for the treatment of neovascular (wet) age-related macular degeneration (wet AMD) in the US grew 7% in 2008, driven primarily by an increased number of Lucentis dosage per patient. New patient share was broadly stable as off-label usage of an unapproved therapy in wet AMD remained high. Outside the US, Lucentis is marketed by Novartis.●Tamiflu 【2008】
Sales of Tamiflu in 2008 declined by 1.5 billion Swiss francs or 68% versus 2007. Seasonal sales were 143 million Swiss francs higher and pandemic sales decreased by 1.6 billion Swiss francs compared to 2007, as most stockpiling programmes from governments and corporations were completed in 2007. Seasonal sales of Tamiflu in Japan were negatively affected by the mild 2007/2008 flu season. In addition, there was a substantial decrease in pandemic sales to the Japanese government.●Mircera(methoxy polyethylene glycol-epoetin beta) 【2007】
Following EU marketing approval in July, Mircera (methoxy polyethylene glycol-epoetin beta), Roche’s innovative continuous erythropoietin receptor activator for the treatment of anemia associated with chronic kidney disease (CKD), has now been launched in Germany, the United Kingdom, Ireland, Sweden, Austria, Slovenia and Hungary, as well as Norway and Switzerland. Initial sales have been in line with expectations. In November, the FDA approved Mircera for the same indication, and further applications for marketing approval are pending worldwide. Mircera allows stable hemoglobin levels with once-monthly dosing during maintenance treatment. It enables correction of anemia with twice-monthly dosing and direct conversion from dosing schedules of up to three times a week with other ESAs to once-monthly dosing in all CKD patients.●Actemra (tocilizumab) リウマチ 【2008】
Actemra/RoActemra (tocilizumab) is a first-in-class therapy based on IL-6 inhibition, representing a novel approach to the treatment of patients with moderate to severe RA. Following approval in April of Actemra for RA in adults and for related pediatric disorders and the subsequent rollout by Chugai, sales uptake in Japan has been very encouraging. In December the Swiss authorities approved RoActemra for the treatment of moderately severe to severe, active rheumatoid arthritis in adult patients who have not responded adequately to treatment with DMARDs or TNF inhibitors. Roche received EU marketing approval for RoActemra in the same indication in January 2009. In September, in a complete response letter to Roche’s US marketing application for Actemra, the FDA requested additional documentation.Following further discussions and as a result of the FDA’s evolving Risk Evaluation and Mitigation Strategy (REMS) requirements for medications, in December the agency asked Roche to prepare a REMS plan for Actemra. In addition, based on the evolving requirements for approval of new biologics, the FDA has asked Roche for non-clinical animal model data, beyond that which was included in the original marketing application. Roche is performing the requested preclinical studies and expects to submit the complete response for Actemra to the FDA in the third quarter of 2009. The FDA has not requested additional clinical studies prior to approval.
【2007】
Actemra (tocilizumab) is a first-in-class humanised monoclonal antibody designed to block the effects of interleukin-6 (IL-6), a key protein involved in the inflammation that drives RA. In 2007 four phase III trials reported significant clinical benefits for a wide range of RA patients who received Actemra. Based on these results, Roche filed marketing applications for Actemra in RA in the US and the EU in November. The Japanese authorities are reviewing an application filed by Chugai in 2006 for approval of Actemra in adult RA and systemic onset juvenile idiopathic arthritis.●Ocrelizumab(R-1594) リウマチ(ヒト化抗CD-20抗体) P3 【2008】 【2007】
Ocrelizumab is a humanised anti-CD20 monoclonal antibody being developed by Roche and Genentech for the treatment of autoimmune diseases. Like MabThera/Rituxan, ocrelizumab also targets B cells. As a humanised antibody, it has the potential to be less immunogenic, better tolerated and more convenient to administer. An extensive global phase III clinical development programme was started in 2007, including three phase III trials in rheumatoid arthritis and phase III trials in systemic lupus erythematosus and lupus nephritis. A phase II programme in relapsing-remitting multiple sclerosis will be initiated in the first half of 2008.●Pertuzumab (R1273) 乳癌 【2008】Pertuzumab (R1273), currently being studied in combination with Herceptin and standard chemotherapy in HER2-positive breast cancer, entered phase III development in 2008. Pertuzumab inhibits the pairing of HER2 with other HER receptors, a key mechanism of tumour growth. CLEOPATRA, a phase III study evaluating the addition of pertuzumab to Herceptin and chemotherapy in first-line treatment of patients with advanced disease, commenced in the first quarter of 2008. In addition, NEOSPHERE, a phase II trial investigating neoadjuvant (presurgical) treatment with pertuzumab, started in the first half of the year. Data from a phase II trial (17929) presented at ASCO 2008 showed that half of the patients with advanced HER2- positive breast cancer whose disease had progressed during previous treatment with a regimen including Herceptin benefited from a combination of Herceptin and pertuzumab. ●Trastuzumab-DM1 (T-DM1,R3502) 乳癌 【2008】Trastuzumab-DM1 (T-DM1, R3502) is a novel antibody.drug conjugate linking trastuzumab (the active ingredient of Herceptin) and the cytotoxic agent DM1. By targeting the HER2 proteins expressed by tumours, the conjugate delivers chemotherapy to the cancer cells in a precise manner. T-DM1 has shown promising clinical efficacy and good tolerability in phase II clinical trials in women with HER2-positive metastatic breast cancer. Roche and Genentech have decided to move T-DM1 into phase III development for second-line HER2-positive metastatic breast cancer; the first trial in this programme is scheduled to start in the first half of 2009. ●R1507 乳癌、肺癌 【2008】R1507 is a monoclonal antibody targeting the IGF-1R receptor. The IGF pathway is important for the growth and survival of a variety of cancers. R1507 is well tolerated and is currently in phase II development for sarcoma, non-small cell lung cancer, and breast cancer. ●R7159 (GA101) 悪性リンパ腫 【2008】R7159 (GA101), a fully humanised, type II, glycoengineered third-generation anti-CD20 monoclonal antibody developed by GlycArt and Roche, is being co-developed with Chugai, Genentech and Biogen Idec for the treatment of CD20-positive hematological malignancies, including CLL and NHL. R7159 targets the same B cell protein (CD20) as MabThera/Rituxan and has been engineered to increase both direct and indirect tumour cell death, thereby enhancing efficacy. In phase I studies R7159 has shown good tolerability and very encouraging clinical activity in patients with no other treatment options who have previously received MabThera/Rituxan. Phase II development in NHL commenced in December. ●R1583 (BIM 51077, licensed from Ipsen)(Taspoglutide) 糖尿病 【2008】Taspoglutide (R1583, BIM 51077, licensed from Ipsen), the first once-weekly human glucagon-like peptide-1 (GLP-1) hormone analogue, is being developed by Roche for type 2 diabetes. The structure of the molecule is similar to that of the natural human hormone. In clinical trials to date, taspoglutide was generally well tolerated and significantly improved glucose control and weight loss after only eight weeks of treatment. Roche initiated an extensive phase III clinical development programme with taspoglutide in July. In late 2008 the FDA issued new guidance on the clinical testing of new treatments for type 2 diabetes. Roche is reviewing the taspoglutide programme to comply with these recommendations. 【2007】
R1583 (BIM 51077, licensed from Ipsen) is a longacting glucagon-like peptide-1 (GLP-1) analogue being developed for the treatment of type 2 diabetes. The structure of the molecule is similar to that of the natural human hormone GLP-1, with potential for weekly or longer administration intervals.
Phase II testing of R1583 was completed in 2007, and the initial data are very encouraging.
Roche expects to make a decision on entry into phase III clinical trials in the first half of 2008.●R1579 糖尿病, a dipeptidyl peptidase IV (DPP-IV) inhibitor 【2008】Phase II development of R1579, a dipeptidyl peptidase IV (DPP-IV) inhibitor, was completed in the second half of the year. While demonstrating adequate glucose reduction and excellent tolerability, the compound did not satisfy Roche’s internal clinical differentiation criteria for transition into phase III testing, and Roche has therefore decided to outlicense it. 【2007】
R1579, a dipeptidyl peptidase IV (DPP-IV) inhibitor being developed for the treatment of type 2 diabetes, moved into phase II clinical testing in 2007. DPP-IV is an enzyme responsible for the breakdown of GLP-1, a hormone involved in blood sugar regulation.●R7204 糖尿病 【2008】R7204 is a novel inhibitor of B-Raf kinase being co-developed by Plexxikon and Roche. Currently in phase I testing, R7204 selectively targets the product by 2025. According to the WHO, type 2 (adult onset) diabetes accounts for around 90% of all cases. ●aleglitazar(R1439) 糖尿病PPAR agonist 【2008】aleglitazar (R1439), is a dual PPAR agonist that has demonstrated effects on blood fats, blood pressure and blood glucose. Phase II clinical testing is nearing completion, and Roche expects to make a decision in the first half of 2009 on phase III development of the compound. ● 【2008】
●Roche AG ●Products ●Research and Development ★Pharmaceuticals Pipeline ●Media ★Media Releases ●Investor Relations ★Investor Update～ニュースリリース Strong operating performance for Roche in 2009[2010.2.3] Reminder: Roche's Full Year Results for 2008[2009.2.3] Reminder: Roche`s Full Year Results and Report for 2007[2008.1.29] Record operating results for Roche again in 2007[2008.1.30] Chugai: A Revision of Financial Outlook for Fiscal Year 2005 (January 1 ~ December, 2005)[2005.4.5] Reminder - Roche´s Full Year Results and Report for 2004[2005.2.1] Roche's Full Year Results and Report 2003[2004.1.26] Roche in 2003: growth significantly outpaces global market - strong operating performance - net income of 3.1 billion Swiss francs[2004.2.4] ★Annual Reports Annual Results 2011 Annual Results 2010 - [Business Report,pdf] - [Finance Report,pdf] Annual Results 2009 [Business Report,pdf,126p] - [Finance Report,pdf,148p] --[Business Report]Pharmaceuticals 39p- にTop-selling products Annual Results 2008 [Business Report,pdf,126p] - [Finance Report,pdf,148p] --[Business Report]Pharmaceuticals 39p- にTop-selling products Annual Results 2007 [Business Report] - [Finance Report]
●Roche -USA ●Products| Newsroom| New Products| Product pipeline Business.com :Roche
●中外製薬 医療関係者向けページ ●ニュースリリース 決算補足資料 平成14年3月 --- 損益計算書の状況②主要製商品別売上高 新製品開発状況 平成14年10月3日[pdf] ●日本ロシュ ★→サイト閉鎖 ニュース ●医療医薬品情報 ・製品学術情報 ---使用上の注意解説(副作用初期症状等含む)、添付文書、インタビューフォーム、くす りのしおり等の日本ロシュ製品の適正使用に関する情報を掲載しています。 ・FAX情報サービス ---日本ロシュの情報提供サービスの総合案内的ページです。こちらから適正使用に関す る情報のダウンロードやFAX自動配信サービスの申し込みもできます。 ・腫瘍領域 ---ラジオ番組 Roche Cancer Today、 腫瘍関連リンク集；Her2Net ・骨代謝領域 ---Bone-Net Osteoprosis患者教育スライド、RICH BONE ・肝炎領域 ---C型肝炎・B型肝炎に関する情報、東京肝臓友の会 ・HIV関連 ---ロシュ・グループ全体のHIV関連情報、米国ガイドライン等 ・インフルエンザ領域 インフルエンザのすべて、素材集、関連リンク ・中枢神経領域 ---パーキンソン病、脳のクリップアート ・治験について ●「日本ロシュ 飛翔の年を迎えて」2001年の業績と2002年の見通し[02.2.13] --- http://www.nipponroche.co.jp/news/2002/n020213.html 2001年売上は750億円、対前年比14.1%増、うち医療用医薬品は720億円、17.3%増を記録。 このうち直販が577億円、21.3%もの大幅増となった。 売り上げ増に貢献したのは、昨年上市の三品目（薬価ベース) 「タフミル」 78億円 01.2発売 Ａ型・Ｂ型抗インフルエンザ薬 「ハーセプチン」 17億円 01.6発売 抗ＨＥＲ２ヒト化モノクローナル抗体 「リツキサン」 24億円 01.9発売 Ｂ細胞性非ホジキンリンパ腫治療薬 「カイトリル」 119億円 01.2継承 制吐剤。スミスクライン・ビーチャムから継承 「フルツロン」 236 抗悪性腫瘍剤 脳血管障害性精神症状改善剤ドラガノンが市場撤退したが、カイトリルがドラガノンの穴 を埋めた格好となっている。 開発品では、抗悪性腫瘍剤カペシタビンの申請を完了し、現在、承認を待っている状態で す。C型肝炎治療剤ペグ・インターフェロンは今年中に申請の予定です。また、肥満症治 療薬オルリスタットは開発に着手いたしました。現在、フェーズＩＩが進行中です。 開発部門では、二次性副甲状腺機能亢進症治療剤のロカルトロール（注射）と抗悪性腫瘍 剤のハーセプチンが四月に承認を受けました。 抗A型・B型インフルエンザ・ウィルス剤のタミフルはドライシロップ剤を昨年七月に申請 し、今年一月に承認を受けました。同じくタミフルのカプセル剤は一部変更申請を行い、 37.5Kg以上の小児への投与が昨年十二月に承認されました ●Roche: UBS Warburg Global Pharma Conference ,Tokyo 20 June 2002[pdf, 全76pの] - 60p "Nippon Roche - Historical Sales" (JPY Million) 2001 2000 1999 Fultulon 19,576(-) 19,575(+2.3) 19,136 5'DFUR 制癌剤 Kytril 9,430 308(-) - granisetrone 制吐剤 Rhypnol 4,236(+2.9) 4,115(+8.8) 3,782 flunitrazepam 抗不安、催眠鎮静 Rocephin 4,063(+0.4%) 4,048(+11.3) 3,637 Rocaltrol oral 3,251(+0.1) 3,248(+4.2) 3,116 Madopar 1,599(+3.2) 1,550(+6.9) 1,450 Tigason 1,429(-9.3) 1,575(+5.6) 1,491 Rivotril 1,287(+4.0) 1,237(+9.4) 1,131 Tamiflu 6,283(-) - - Herceptin 1,399(-) - - Rituxan 2,023(-) - - CellCept 1,101(+67.6) 657() 43 Draganon - 8,404 12,558
●Genentech, Inc
- http://www.gene.com/gene/index.jsp; 創薬バイオ企業として成功伝説トップ３の一つ。 近年は抗体医薬で次々と大型新薬を創出し 特にRoche社製品の中核を構成。 Roche社は1999年から積極的にGenentechへの資本参加を求め、2007.12末 Roche社が株式の55.8%を支配。 2008年7月に全株式買収に両社が合意した。 1976.4.7 創立(ベンチャー投資家Robert A. Swansonと生化学者Dr. Herbert W. Boyer) 1977. somatostatinの生産開始 1980 株式公開 1982 初のDNA 組織培養human insulinを発売、Eli Lilly に供給 1984 初のFactor VIII生産に成功、Cutter Biologicalに世界生産・販売権をライセンス 1985 初のバイオ技術による人成長ホルモンProtropin(R) (somatrem for injection)のFDA承認 1986 interferon alpha-2a (ヘアリーセル白血病)のFDA承認。 Rocheにライセンス(Roferon) 1987 Activase(R)(Alteplase, recombinant), a tissue-plasminogen activator (t-PA)のFDA承認 1987 再組織化 本社Delaware 1990 Hepatitis B vaccineのFDA承認。 GSKにライセンス。 Genentech and Roche Holding Ltd. of Basel, Switzerland completed a $2.1 billion merger1993
- Genentech received FDA approval to market Nutropin® [somatropin (rDNA origin) for injection] for treating growth failure in children with chronic renal insufficiency before they undergo kidney transplantation.
- Genentech received approval to market Pulmozyme® (dornase alfa) for treating cystic fibrosis from regulatory agencies in the United States, Canada, Sweden, Austria and New Zealand.
- Genentech's Factor VIII — licensed to Miles Inc. (formerly Cutter Biological) in 1984 — received FDA approval for the treatment of hemophilia-A.
1994
- Genentech announced it would locate its new manufacturing facility in Vacaville, California.
- Genentech received FDA approval to market Nutropin for the treatment of children with growth failure due to inadequate levels of the natural growth hormone in their bodies.
1995
- Genentech announced an agreement with Roche Holding, Ltd. to extend for four years Roche's option to purchase the outstanding redeemable common stock of the company at a predetermined price that escalates quarterly up to $82.50 a share. As part of the agreement, Genentech began receiving royalties rather than recording sales on European sales of Pulmozyme and Canadian sales of all Genentech products as Roche assumed responsibility for those sales.
- Genentech received FDA approval to market an accelerated infusion regimen of Activase® for the management of acute myocardial infarction.
1996
- Genentech celebrated the 20-year anniversary of its founding.
- Genentech received FDA approval to market Nutropin AQ® [somatropin (rDNA origin) injection] for the treatment of growth failure in children with chronic renal insufficiency before they undergo kidney transplantation and for the treatment of growth hormone deficiency in children.
- Genentech received FDA approval to market Activase for the treatment of acute ischemic stroke or brain attack.
- Genentech received FDA approval to market Pulmozyme for treating cystic fibrosis patients with advanced disease.
1997
- Genentech and partner IDEC Pharmaceuticals (now Biogen Idec Inc.) received FDA approval to market Rituxan® (Rituximab) for the treatment of patients with relapsed or refractory low-grade or follicular, CD20 positive, B-cell non-Hodgkins lymphoma.
- Genentech received FDA approval to market Nutropin AQ® for the treatment of short stature associated with Turner syndrome.
- Genentech received FDA approval to market Nutropin® and Nutropin AQ® for the treatment of growth hormone deficiency in adults.
- Genentech launched a service for patients and their physicians called SPOC — Single Point of Contact — to provide customer-focused reimbursement assistance. The program became Genentech Access Solutions in 2008.
- In recognition of the importance of Genentech in establishing the biotechnology industry in South San Francisco, the city renamed the 400 block of Point San Bruno Boulevard to DNA Way, giving Genentech the new street address 1 DNA Way.
1998
- Genentech received approval from the FDA to market the humanized antibody Herceptin® (Trastuzumab) as a first-line therapy in combination with paclitaxel and as a single agent in second- and third-line therapy for patients with metastatic breast cancer who have tumors that overexpress the HER2 (human epidermal growth factor receptor2) protein.
- Genentech dedicated its new $250 million manufacturing facility in Vacaville.
1999
- Genentech co-founder Robert Swanson was awarded (posthumously) the National Medal of Technology for his foresight and leadership in recognizing the commercial promise of recombinant DNA technology and his seminal role in the establishment and development of the biotechnology industry.
- Genentech reached a settlement agreement with the U.S. Attorney for the Northern District of California regarding Genentech's promotion of human growth hormone in the late 1980s and early 1990s.
- Roche exercised its option to cause Genentech to redeem all of its outstanding special common shares not owned by Roche. Roche announced its intent to publicly sell up to 19 percent of Genentech shares and continue Genentech as a publicly traded company with independent directors.
- Genentech received FDA approval of additional efficacy results for its growth hormone products - Nutropin® and Nutropin AQ® - on the effects of growth hormone replacement therapy on spine bone mineral density in young adults with childhood-onset growth hormone deficiency (GHD).
- On July 20, after about a month-long hiatus due to the Roche redemption, Genentech returned to the New York Stock Exchange (NYSE) with a public reoffering of 22 million shares by Roche, in what is considered the largest public offering in the history of the U.S. health care industry. The stock closed the first day of trading at $127, over 31 percent above the public offering price of $97. This was also the first introduction of Genentech's new NYSE trading symbol, DNA.
- Roche conducted a secondary offering of 20 million Genentech shares on October 20. The shares were priced at $143.50 per share, making it the largest secondary offering in U.S. history.
- Genentech and the University of California (UC) agreed to a settlement of the patent infringement lawsuit brought by UC relating to the company's human growth hormone product, Protropin. Both parties agreed that this settlement was not an admission that Genentech infringed UC's patent or used the genetic material in question.
- Genentech and partner Alkermes, Inc. received FDA approval to market Nutropin Depot® [somatropin (rDNA origin) for injectable suspension] for the long-term treatment of growth failure due to a lack of adequate endogenous GH secretion.
2000
- Roche conducted a third offering of up to 19 million shares of Genentech stock at $163 per share.
- Genentech announced the purchase of a cell culture manufacturing facility in Porriño, Spain. Genentech sold the facility to Lonza in 2006.
- Genentech's state-of-the-art manufacturing facility in Vacaville, Calif., received FDA licensure as a multi-product facility.
- Genentech received FDA approval of TNKase® (Tenecteplase) for the treatment of acute myocardial infarction (heart attack).
2001
- Genentech celebrated the 25th anniversary of its founding.
- Cathflo® Activase® (Alteplase) was approved by the FDA for the restoration of function to central venous access devices (CVADs).
2002
- The FDA approved Nutropin AQ PEN® for delivery of Nutropin AQ® recombinant growth hormone.
- A Los Angeles County Superior Court jury voted to award the City of Hope (COH) $300 million in additional royalties and $200 million in punitive damages in the retrial of a contract dispute lawsuit brought by COH against Genentech. Genentech announced it would appeal the judgment in the case to the California Court of Appeal.
- Genentech received FDA approval to include HER2 gene detection test in Herceptin product labeling.
2003
- Genentech received FDA approval for Xolair® (Omalizumab) for Subcutaneous Use for moderate-to-severe persistent asthma in adults and adolescents. Xolair is the first humanized therapeutic antibody for the treatment of asthma and the first approved therapy designed to target the antibody IgE, a key underlying cause of the symptoms of asthma that has an allergic component.
- Genentech received FDA approval for Raptiva® (efalizumab) for the treatment of chronic moderate-to-severe plaque psoriasis in adults age 18 or older who are candidates for systemic therapy or phototherapy. Raptiva is the first biologic therapy that is designed to provide continuous control of chronic moderate-to-severe plaque psoriasis and can be self-administered by patients as a single, once-weekly, subcutaneous injection.
2004
- Genentech received FDA approval for Avastin® (bevacizumab) for use in combination with 5-Fluorourcil-based chemotherapy in the treatment of first-line metastatic cancer of the colon or rectum. Avastin is the first FDA-approved therapy designed to inhibit angiogenesis, a process fundamental to cancer growth and metastasis.
- Genentech broke ground on an expansion of the Vacaville site. When completed, the new facility will be configured with an additional eight 25,000-liter fermentation tanks and, when combined with our existing facility, will be the largest biotechnology cell culture manufacturing site of its kind in the world.
- OSI Pharmaceuticals and Genentech announced that the FDA approved, after priority review, Tarceva® (erlotinib) for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one prior chemotherapy regimen. Tarceva is an oral tablet indicated for daily administration.
2005
- Genentech purchased Biogen Idec's Oceanside, California, biologics manufacturing facility.
- Genentech received FDA approval for Tarceva (100 mg) in combination with gemcitabine chemotherapy for the treatment of locally advanced, inoperable or metastatic pancreatic cancer in patients who have not received previous chemotherapy.
2006
- Genentech celebrated the 30th anniversary of its founding.
- Genentech received approval from the FDA for Lucentis® (ranibizumab injection) for the treatment of neovascular (wet) age-related macular degeneration.
- Genentech received FDA approval for Rituxan for use in combination with methotrexate for reducing signs and symptoms in adult patients with moderately- to severely-active rheumatoid arthritis who have had an inadequate response to one or more tumor necrosis factor antagonist therapies.
- Genentech received FDA approval for Herceptin as part of a treatment regimen containing doxorubicin, cyclophosphamide and paclitaxel, for the adjuvant treatment of patients with HER 2-positive, node-positive breast cancer.
- Genentech and Lonza finalized an agreement for Lonza to purchase Genentech's manufacturing facility in Porriño and to continue to supply Avastin for Genentech under a supply agreement. Concurrently, Genentech entered into a supply agreement for the manufacture of certain Genentech products at Lonza's facility currently under construction in Singapore, with the right to exercise an exclusive option to purchase the facility between 2007 and 2012.
2007
- In August 2007, Genentech finalized its acquisition of Tanox, enabling Genentech to improve the Xolair business and acquire Tanox's product pipeline.
- Genentech was named by Science magazine as a top employer and most admired company in the in the biotechnology, biopharmaceutical, pharmaceutical and related industries for the sixth year in a row.
- Genentech was named one of the "100 Best Companies for Working Mothers" by Working Mother Magazine for the 15th year.
2008
- FORTUNE named Genentech one of the "100 Best Companies to Work For" for the tenth consecutive year. This year Genentech was number five on the list.
- Genentech received FDA approval for Herceptin as a singe agent, for the adjuvant treatment of HER2-overexpressing node-negative (ER/PR-negative or with one high risk feature) or node-positive breast cancer, following multi-modality anthracycline-based therapy.
- Genentech received FDA approval for its supplemental Biologics License Application (sBLA) to expand the label for Rituxan to treat adult patients with moderate-to-severe rheumatoid arthritis (RA) in combination with methotrexate (MTX) to slow the progression of structural damage.
- In April 2008, The California Supreme Court overturned the award of $200 million in punitive damages resulting from the contract dispute lawsuit brought by City of Hope against Genentech.
- In July 2008, Genentech received a proposal from Roche to acquire all of the outstanding shares of Genentech stock not owned by Roche at a price of $89.00 in cash per share. A special committee of independent directors concluded that Roche's proposal substantially undervalues the company but stated it would consider a proposal that recognizes the value of the company.
●会社決算●Products ●Press Release ●Financials Annual Report 2008 Annual Report 2007 Annual Report 2006 Annual Report 2005 Annual Report 2004 ★SEC Filings Form 10-K[2009.2.20;pdf,140p] Form 10-K[2008.2.26;pdf,122p] Form 10-K[2007.2.23;pdf,103p] 2005 Form 10-K[2006.2.17;pdf,103p] 10-K[2005.2.28,pdf,110p] Historical Product Sales ●Pipeline ●売上
($ milllion) 2008 2007 2006 2005 2004 2003 2002 収入 合計 13,418(+14) 11,724(+26) 9,284(+40) 6,633.4(+44) 4,621.2(+40) 3,300.2(+28) 2,583.7 製品売上高 計 10,531(+12) 9,443(+24) 7,640(+39) 5,488.1(+46) 3,748.9(+43) 2,621.4(+21) 2,163.6 ロイヤリティ 2,539(+28) 1,984(+47) 1,354(+45) 935.1(+46) 641.1(+28) 500.9(+37) 365.6 契約収入 348(+17) 297(+2) 290(+38) 210.2(-9) 231.2(+30) 177.9(+226) 54.5 営業利益 5,329(+26) 4,229(+34) 3,152(+64) 1,921.9(+69) 1,136.8(+41) 804.6 (78.0) 経常利益 5,431(+23) 4,426(+30) 3,403(+69) 2,012.9(+65) 1,219.4(+36) 897.4(+2911) 30.0 純利益 3,427(+24) 2,769(+31) 2,113 1,279.0(+63) 784.8(+40) 562.5(+782) 63.8 研究開発費 2,800(+14)[21%] 2,446(+38)[21%] 1,773(+40)[19%] 1,261.8(+33) 947.5(+31) 722.0(+16) 623.5 従業員数 11,186 11,174 10,533 9,563 7,646 6,226 5,252 ●導出先一覧 [2007年報より]
($ milllion) 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 備考 製品売上高 計 10,531(+12) 9,443(+24) 7,640(+39) 5,488.1(+46) 3748.9(+43) 2621.4(+21) 2163.6 1,742.9 1,278.4 1,039.1 717.7 Avastin 2,908 2,453 1,853 1,182.5 554.5 - (発売2004.2) - - - (bevacizumab)大腸癌 米国内 2,686(+17) 2,296(+32) 1,746(+54) 1,132.9(+108) 544.6 - - - - - - 提携先向 222 157 107 49.6 9.9 - - - - - - Roche(米国外) Rituxan 2,851 2,515 2,252 1,989.3 1711.2(+15) 1489.1(+28) 1162.9 818.6 444.1 279.4 162.6 rituximab 悪性リンパ腫 米国内売上 2,587(+13) 2,285(+10) 2,071(+13) 1,831.4(+16) 1,574.0 1,360.2 1080.2 779.0 424.2 262.7 152.1 提携先向 264 230 181 157.9 137.2 128.9 82.7 39.6 19.9 16.7 10.4 Roche(米日外) Herceptin 1,819 1,704 1,330 764.2 483.2(+14) 424.8(+10) 385.2 346.7 276.0 188.4 30.5 [trastuzumab]乳癌治療剤 米国内売上 1,382(+7) 1,287(+4) 1,234(+65) 747.2(+56) 479.0 406.0 344.9 315.4 249.7 183.7 30.5 提携先向 437 417 96 17.0 4.2 18.8 40.3 31.3 26.3 4.7 0.0 Roche(米国外) Lucentis 887 825 381 - - - - - - - - [ranibizumab]AMD(黄斑変性)FDA承認2006.6.30 米国内 875(+7) 815(+114) 380(-) - - - - - - - - 提携先向 12 10 1 - - - - - - - - Novartis(米国外) Xolair 517 472 429 327.6 188.5(+645) 25.3(-) - - - - - (Omalizumab)喘息;抗IgE抗体 米国内 517(+10) 472(+11) 425(+33) 320.6(+70) 187.6 25.1 - - - - - 提携先向 - - 4 7.0 1.0 0.2 - - - - - Novartis(米国外) Tarceva米国内 457(+10) 417(+4) 402(+46) 274.9(-) 13.3 - (発売2004.11.22) - - (erlotinib)肺癌;(米国外Roche) Protropin/Nutropin 375 384 386 375.3 353.6 321.9 297.2 250.2 226.6 221.2 214.0 HGH;ヒト成長ホルモン 米国内 358(-4) 371(-2) 378(+2) 370.5(+6) 348.8 319.5 294.6 248.6 225.3 220.2 213.2 提携先向 17 12 8 4.8 4.8 2.5 2.6 1.6 1.4 1.0 0.8 Roche(加) Thrombolytics 286 288 259 226.8 200.0(+8) 185.2(+3) 180.2 197.1 206.2 236.0 213.0 (Activase/TNKase/Cathflo Activase) 米国内 275(+3) 268(+10) 243(+11) 218.5(+12) 194.5 181.2 175.0 187.4 202.1 232.7 210.2 提携先向 11 20 16 8.3 5.5 4.0 5.2 9.7 4.1 3.3 2.7 Roche(加) Pulmozyme 305 266 244 221.9 177.7(+6) 167.2(+21) 138.1 122.9 121.8 111.4 93.8 (dornase alfa) cystic fibrosis 米国内 257(+15) 223(+12) 199(+7) 186.5(+18) 157.1 143.7 123.3 110.2 105.9 95.8 79.6 提携先向 48 43 45 35.4 20.6 23.5 14.8 12.8 15.8 15.5 14.3 Roche(米国外) Raptiva 125 119 104 94.1 56.3(+3921) 1.4(-) - - - - - (efalizumab) Psoriasis 米国内 108(+1) 107(+19) 90(+14) 79.2(+52) 52.4 1.4 - - - - - 提携先向 17 12 14 14.9 3.9 - - - - - - Enbrel提携先向 - - - 31 11 - - - - - - [Etanercept]関節リウマチ その他 - - - 31.5 10.6 6.5 - 7.3 3.7 2.7 3.9 米国内 - - - - - - - - - - - 提携先向 - - - 31.5 10.6 6.5 - 7.3 3.7 2.7 3.9 製品売上高 計 10,531(+12) 9,443(+24) 7,640(+39) 5,488.1(+46) 3,748.9 2,621.4 2,163.6 1,742.9 1,278.4 1,039.1 717.7 米国内 9,503(+11) 8,540(+19) 7,169(+39) 5,161.7(+45) 3,551.2 2,437.6 2,018.0 1,640.6 1,207.3 995.0 685.5 提携先向 1,028(+14) 903(+92) 471(+44) 326.4(+65) 197.7 183.8 145.6 102.3 71.1 44.1 32.1 []
製品名 商品名 導出先企業 地域 Trastuzumab Herceptin Hoffmann-La Roche 米国を除く全世界 Rituximab Rituxan/MabThera Hoffmann-La Roche 米・日を除く全世界 Bevacizumab Avastin F. Hoffmann-La Roche 米国を除く全世界 Dornase alfa,recombinant Pulmozyme Hoffmann-La Roche 米国を除く全世界 Alteplase and Tenecteplase Activase and TNKase Hoffmann-La Roche Canada Somatropin Nutropin F. Hoffmann-La Roche Canada Daclizumab Zenapax F. Hoffmann-La Roche 米国を除く全世界 Ranibizumab Lucentis Novartis 米国を除く全世界 Etanercept ENBREL Immunex Corporation
(権利はAmgenにより買収)Worldwide adalimumab Humira Abbott Worldwide Infliximab Remicade Celltech Pharmaceuticals plc (権利はCentocor /Johnson & Johnsonに移転) Worldwide ●以下は旧データ[2005年報より] Antihemophilic factor,recombinant(Factor VIII) Kogenate/Helixate Bayer Corporation Worldwide Alteplase, recombinant Actilyse Boehringer Ingelheim 米・加・日以外の多数 Tenecteplase Metalyse Boehringer Ingelheim 米・加・日以外の多数 Cetuximab ERBITUX(R) ImClone Systems, Inc. Worldwide
★Herceptin(trastuzumab) 【2007】
Net U.S. sales of Herceptin increased 4% to $1,287 million in 2007 and 65% to $1,234 million in 2006. The sales growth in 2007 and 2006 was due to price increases that occurred from 2005 through 2007, and increased use of Herceptin in the treatment of early-stage HER2-positive BC (approved on November 16, 2006). We estimate Herceptin’s penetration in the adjuvant setting was approximately 75% at the end of 2007. In first-line HER2-positive metastatic BC patients, we estimate Herceptin’s penetration remained flat at approximately 70% from the end of 2006.
On January 18, 2008, the FDA expanded the Herceptin label, based on the HERA study, for the treatment of patients with early-stage HER2-positive BC to include treatment for patients with node-negative BC. Herceptin also may now be administered for one year in an every-three-week dosing schedule, instead of weekly.【2007競合】
Herceptin: Herceptin faces competition in the relapsed metastatic setting from Tykerb(R) (lapatinib ditosylate), manufactured by GSK. On March 13, 2007, the FDA approved Tykerb(R), in combination with capecitabine, for the treatment of patients with advanced or metastatic BC whose tumors overexpress HER2 and who have received prior therapy, including an anthracycline, a taxane, and Herceptin. Market research indicates that lapatinib use in the fourth quarter was primarily within the later lines of metastatic BC. We will continue to monitor the clinical development of lapatinib in early lines of metastatic and adjuvant breast cancer.★Xolair(omalizumab) 【2007】
Net U.S. sales of Xolair increased 11% to $472 million in 2007 and 33% to $425 million in 2006. Sales growth in 2007 and 2006 was driven by increased penetration in the asthma market and, to a lesser extent, price increases effective between 2005 and 2007. At the FDA’s request, we and Novartis, our co-promotion collaborator, updated the Xolair product label in June 2007 with a boxed warning regarding the risk of anaphylaxis in patients receiving Xolair. We believe that this update had a minimal effect on sales of Xolair in 2007. Genentech is working with the FDA to finalize a Risk Minimization Action Plan that emphasizes the incidence of anaphylaxis and instructs physicians that patients should be closely observed for an appropriate period of time after Xolair administration.【2006】
Net U.S. sales of Xolair increased 33% to $425 million in 2006 and 70% to $320 million in 2005. Sales growth in 2006 and 2005 were driven by increased penetration in the asthma market and, to a lesser extent, price increases effective on July 21, 2005, April 4, 2006, and October 17, 2006.
On February 21, 2007, the FDA announced it requested that Genentech strengthen the existing warning on the potential risk for anaphylaxis in patients receiving Xolair by adding a boxed warning to the product label and implementing a Risk Mitigation Action Plan, including providing a medication guide for patients. Genentech and Novartis will be working with FDA on its request.【2007競合】
Xolair faces competition from other asthma therapies, including inhaled corticosteroids, long-acting beta agonists, combination products such as fixed-dose inhaled corticosteroids/long-acting beta agonists and leukotriene inhibitors, as well as oral corticosteroids and immunotherapy.【competition 2006】
Xolair: Xolair faces competition from other asthma therapies, including inhaled corticosteroids, long-acting beta agonists, combination products such as fixed dose inhaled corticosteroids/long-acting beta agonists and leukotriene inhibitors, as well as oral corticosteroids and immunotherapy.【acquisition 2006】
On November 9, 2006 we and Tanox Inc. announced that we entered into an agreement to acquire Tanox, a biotechnology company specializing in the discovery and development of biotherapeutics based on monoclonal antibody technology, for $20 per share for a total cash value of approximately $0.9 billion.We and Tanox have been working together in collaboration with Novartis since 1996 to develop and commercialize Xolair. The terms of the acquisition have been unanimously approved by the Boards of Directors of both companies and approved by the stockholders of Tanox. We received a request for additional information from the U.S. Federal Trade Commission (or “second request”) in connection with the proposed acquisition. The second request extends the waiting period imposed by the Hart-Scott-Rodino Antitrust Improvements Act of 1976 (or “Hart-Scott-Rodino Act”). The transaction is expected to be completed within the first half of 2007, subject to satisfaction of certain closing conditions, including the absence of a material adverse effect with respect to Tanox and the expiration or termination of the waiting period under the Hart-Scott-Rodino Act. Funds will be provided from Genentech’s cash on hand at the time of closing. We are currently evaluating the effects of the acquisition on our results of operations and financial condition and expect that if the transaction closes a substantial portion of the purchase price will be expensed as in-process research and development (or “R&D”).【Novartis 2006】
We, along with Novartis Pharma AG and Tanox, Inc., are co-developing Xolair in the U.S., and we and Novartis are co-promoting Xolair in the U.S. and both make certain joint and individual payments to Tanox; our joint and individual payments are in the form of royalties. We record all sales and cost of sales in the U.S. and Novartis markets the product in and records all sales and cost of sales in Europe.We and Novartis share the resulting U.S. and European operating profits, respectively, according to prescribed profit-sharing percentages. On January 20, 2006, Novartis received FDA approval to manufacture bulk supply of Xolair at their Huningue production facility in France. We now acquire bulk supply of Xolair from Novartis and compensate them on a cost plus mark up basis.●Avastin (bevacizumab) 【2007】
Net U.S. sales of Avastin increased 32% to $2,296 million in 2007 and 54% to $1,746 million in 2006. Net U.S. sales in 2007 included the net recognition of $7 million of previously deferred revenue, mostly due to lower than expected enrollment in our Avastin Patient Assistance Program. The increase in sales in 2007 was primarily a result of increased use of Avastin in first-line metastatic NSCLC, approved on October 11, 2006, and in metastatic BC, an unapproved use of Avastin during 2007.
Among first-line metastatic NSCLC patients, we estimate that Avastin penetration was approximately 35% in the fourth quarter of 2007. Among the approximately 50%-60% of patients in first-line metastatic lung cancer who are eligible for Avastin therapy, we estimate that penetration was approximately 60%. With respect to dose, use of the 15mg/kg/every-three-weeks dose during the fourth quarter of 2007 remained stable relative to the third quarter of 2007 at approximately 60%-65%.We expect dose in metastatic NSCLC to continue to be a source of uncertainty for Avastin. The Roche-sponsored BO17704 study, which was presented at the American Society of Clinical Oncology in June 2007, evaluated a 15mg/kg/every-three-weeks dose of Avastin (the dose approved in the U.S. for use in combination with carboplatin and paclitaxel) and a 7.5mg/kg/every-three-weeks dose of Avastin (a dose not approved for use in the U.S.) in combination with gemcitabine and cisplatin chemotherapy compared to chemotherapy alone in patients with previously untreated, advanced NSCLC. Both doses met the primary endpoint of prolonging PFS compared to chemotherapy alone. Although the study was not designed to compare the Avastin doses, a similar treatment effect in PFS was observed between the two arms. We also expect overall survival data from the BO17704 study during the first half of 2008. Depending on these results, additional physicians may adopt Avastin at the lower dose of 7.5mg/kg/every-three-weeks.
In first-line metastatic CRC, penetration in the fourth quarter of 2007 was in line with penetration in the fourth quarter of 2006. In second-line CRC, we estimate that Avastin penetration in the fourth quarter of 2007 was consistent with that seen in the fourth quarter of 2006. Increased competition in second-line CRC negatively affected Avastin use in the first half of 2007 but use in CRC has since returned to fourth quarter 2006 levels.
In first-line metastatic BC patients, Avastin adoption in the fourth quarter of 2007 was approximately 25%. Avastin use in this setting has been supported by favorable reimbursement, which is partially due to its Compendia listing.
On February 12, 2008, we announced that AVADO, Roche’s study evaluating two doses of Avastin in first-line metastatic BC, met its primary endpoint of prolonging PFS. Both doses of Avastin in combination with chemotherapy showed statistically significant improvement in the time patients lived without their disease advancing compared to chemotherapy and placebo, although the study was not designed to compare the Avastin doses. The FDA notified us on February 22, 2008 that Avastin received accelerated approval for use in combination with paclitaxel chemotherapy, for patients who have not received prior chemotherapy for metastatic HER2-negative BC. We anticipate increased use of Avastin in breast cancer as a result of this favorable decision.
The increase in sales in 2006 was primarily a result of increased use of Avastin in metastatic NSCLC and metastatic BC, an unapproved use of Avastin during 2006. In addition, the increase reflected modest gains in the treatment of first-line metastatic CRC. These increases were partially offset by declining revenue in metastatic renal cell carcinoma and metastatic pancreatic cancer, which are both unapproved uses.【2007競合】
Avastin: Avastin competes in metastatic colorectal cancer (CRC) with Erbitux(R) (Imclone/Bristol-Myers Squibb), which is an epidermal growth factor receptor (EGFR) inhibitor approved for the treatment of irinotecan refractory or intolerant metastatic CRC patients; and with VectibixTM (Amgen), which is indicated for the treatment of patients with EGFR-expressing metastatic CRC who have disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan- containing regimens. Avastin could also face competition from Erbitux(R) in metastatic NSCLC. In the third quarter of 2007, ImClone Systems Incorporated and Bristol-Myers Squibb Company announced that a Phase III study of Erbitux(R) in combination with vinorelbine plus cisplatin met its primary endpoint of increasing overall survival compared with chemotherapy alone in patients with advanced NSCLC. Data from this study are expected in 2008. In addition, Avastin competes with Nexavar(R) (sorafenib, Bayer Corporation/Onyx Pharmaceuticals, Inc.), Sutent(R) (sunitinib malate, Pfizer, Inc.), and Torisel(R) (Wyeth) for the treatment of patients with advanced renal cell carcinoma (an unapproved use of Avastin).
Avastin could face competition from products in development that currently do not have regulatory approval.
Sanofi-Aventis is developing a VEGF inhibitor VEGF-Trap in multiple indications, including metastatic CRC and metastatic NSCLC. There are also ongoing head-to-head clinical trials comparing both Sutent(R) and AZD2171 (AstraZeneca) to Avastin. Likewise, Amgen has initiated head-to-head clinical trials comparing AMG 706 and Avastin in NSCLC and metastatic breast cancer (BC). Overall, there are more than 65 molecules in clinical development that target VEGF inhibition, and over 130 companies are developing molecules that, if successful in clinical trials, may compete with Avastin.●Rituxan (rituximab) 【2007】
Net U.S. sales of Rituxan increased 10% to $2,285 million in 2007 and 13% to $2,071 million in 2006. Sales growth in 2007 and 2006 resulted from increased use of Rituxan in the oncology setting and in the rheumatoid arthritis setting, and from price increases in both years.
In the oncology setting, the increases came from Rituxan’s use following chemotherapy in indolent NHL, including areas of unapproved use, and chronic lymphocytic leukemia (CLL), an unapproved use.We estimate that Rituxan’s overall adoption rate in combined markets of NHL and CLL increased slightly to approximately 85% at the end of 2007 from approximately 80% at the end of 2006.
Primary drivers of growth in the rheumatoid arthritis setting were increased new patient starts, increased total numbers of prescribers to an estimated 80% of targeted rheumatologists, and a retreatment interval averaging between six and seven months. It remains difficult to precisely determine the sales split between Rituxan use in oncology and immunology settings since many treatment centers treat both types of patients, but we estimate that sales in the immunology setting represented approximately 11% of total Rituxan sales for 2007.
On January 25, 2008, the FDA approved our sBLA to expand the label for Rituxan to include slowing the progression of structural damage in adult patients with moderate-to-severe rheumatoid arthritis who have failed anti- tumor necrosis factor (TNF) therapies. In January 2008, results from Rituxan Phase III SUNRISE trial met its primary endpoint. This study was a controlled retreatment study for patients with rheumatoid arthritis who have had an inadequate response to previous treatment with one or more TNF antagonist therapies. A preliminary review of the safety data revealed no new safety signals. On January 24, 2008 we announced that the SERENE Phase III clinical study of Rituxan in patients who have not been previously treated with a biotherapeutic met its primary endpoint of a significantly greater proportion of Rituxan-treated patients achieving an American College of Rheumatology (ACR) 20 response at week 24, compared to placebo. In this study, patients who received a single treatment course of two infusions of either 500 mg or 1,000 mg of Rituxan in combination with a stable dose of methotrexate displayed a statistically significant improvement in ACR20 scores compared to patients who received placebo in combination with methotrexate. Although the study was not designed to compare the Rituxan doses, treatment efficacy appears to be similar between both Rituxan doses.【2007競合】
Rituxan: Rituxan’s current competitors in hematology-oncology include Bexxar(R) (GlaxoSmithKline [GSK]) and Zevalin(R) (Cell Therapeutics), both of which are radioimmunotherapies indicated for the treatment of patients with relapsed or refractory low-grade, follicular, or transformed B-cell NHL. Other potential competitors include Campath(R) (Bayer Corporation/Genzyme) in previously untreated and relapsed chronic lymphocytic leukemia (CLL) (an unapproved use of Rituxan); Velcade(R) (Millennium Pharmaceuticals, Inc.), which is indicated for multiple myeloma and more recently, mantle cell lymphoma (both unapproved uses of Rituxan); and Revlimid(R) (Celgene), which is indicated for multiple myeloma and myelodysplastic syndromes (both unapproved uses of Rituxan).
Rituxan’s current competitors in rheumatoid arthritis (RA) include Enbrel(R) (Amgen/Wyeth), Humira(R) (Abbott Laboratories), Remicade(R) (Johnson & Johnson), Orencia(R) (Bristol-Myers Squibb), and Kineret(R) (Amgen). These products are approved for use in a RA patient population that is broader than the approved population for Rituxan. In addition, molecules in development that, if approved by the FDA, may compete with Rituxan in RA include: ActemraTM, an anti-interleukin-6 receptor being developed by Chugai and Roche; CimziaTM (certolizumab pegol), an anti-TNF antibody being developed by UCB; and CNTO 148 (golimumab), an anti-TNF antibody being developed by Centocor, Inc. (a wholly owned subsidiary of Johnson & Johnson).
Rituxan may face future competition in both hematology-oncology and RA from Humax CD20TM (Ofatumumab), an anti-CD20 antibody being co-developed by Genmab and GSK. Genmab and GSK announced their plans to file for approval of HumaxTM in 2008 for monotherapy use in refractory CLL and to complete a monotherapy trial for refractory indolent NHL. In addition, we are aware of other anti-CD20 molecules in development that, if successful in clinical trials, may compete with Rituxan. Rituxan could also face competition from Treanda(R) (Cephalon, Inc.), a NHL treatment candidate that showed positive results in Phase III clinical trials for refractory indolent NHL patients and previously untreated CLL patients. There are several therapeutic vaccines currently in development that may seek approval in indolent NHL in the future.●Lucentis (ranibizumab) 【2007】
Lucentis was approved by the FDA for the treatment of neovascular (wet) AMD on June 30, 2006. Net U.S. sales of Lucentis increased 114% to $815 million in 2007 from $380 million in 2006, and sales in the fourth quarter of 2007 decreased 9% to $197 million from the comparable period in 2006. We believe that approximately 50% of newly diagnosed patients were treated with Lucentis during the fourth quarter of 2007, which was flat compared to the third quarter of 2007, and a decrease from 55% in the fourth quarter of 2006. We believe that the main factors affecting Lucentis sales in 2007 were the continued unapproved use of Avastin and reimbursement concerns from retinal specialists. Lucentis received a permanent J-code classification from the Centers for Medicare and Medicaid Services in January 2008, which we believe may address some of the reimbursement concerns. In October 2007 we announced that we planned to no longer allow compounding pharmacies the ability to purchase Avastin directly from wholesale distributors, and this change in distribution was made effective on January 1, 2008. However, physicians can purchase Avastin from authorized distributors and ship to the destination of the physicians' choice.
The unapproved use of Avastin and the change in distribution for Avastin, as well as reimbursement concerns have created a difficult environment for the promotion of Lucentis and the building of relationships with retinal specialists We expect these factors to persist and limit Lucentis sales growth.【2007競合】
Lucentis: We are aware that retinal specialists are currently using Avastin to treat the wet form of AMD, an unapproved use for Avastin, which results in significantly less revenue to us per treatment compared to Lucentis. As of January 1, 2008, we no longer directly supply Avastin to compounding pharmacies. After discussions with the leadership of the American Society of Retina Specialists and the American Academy of Ophthalmology, we expect ocular use of Avastin to continue as physicians can purchase Avastin from authorized distributors and ship to the destination of the physicians’ choice. Additionally, an independent head-to-head trial of Avastin and Lucentis in wet AMD is being partially funded by the National Eye Institute, who announced that it expects to begin enrollment in the next few months. Lucentis also competes with Macugen(R) (Pfizer/OSI Pharmaceuticals), and with Visudyne(R) (Novartis) alone, in combination with Lucentis, in combination with Avastin, or in combination with the off-label steroid triamcinolone in wet AMD. In addition, VEGF-Trap-Eye, a vascular endothelial growth factor blocker being developed by Bayer Corporation and Regeneron, is in Phase III clinical trials for treatment of wet AMD.●Tarceva (erlotinib) Tarceva (erlotinib), which we commercialize with OSI Pharmaceuticals, Inc., is a small-molecule tyrosine kinase inhibitor of the HER1/epidermal growth factor receptor signaling pathway. Tarceva is approved for the treatment of patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen. It is also approved, in combination with gemcitabine chemotherapy, for the first-line treatment of patients with locally advanced, unresectable, or metastatic pancreatic cancer. 【2007】
Net U.S. sales of Tarceva increased 4% to $417 million in 2007 and 46% to $402 million in 2006. Sales in 2007 were positively affected by price increases during 2007 and 2006. These increases, however, were partially offset by product returns and return reserve requirements (which were higher than expected in the second and third quarters of 2007) and by modest decreases in volume in 2007.We estimate that Tarceva’s penetration in second-line NSCLC was 30% in 2007, which was stable compared to 2006. In the first-line pancreatic cancer setting, we estimate that Tarceva’s penetration was 40% in 2007, which was stable compared to 2006.
The increase in product sales in 2006 was due to price increases in 2006 and 2005, and growth in penetration and duration of treatment in both second-line NSCLC and first-line pancreatic cancer.【2007競合】
Tarceva: Tarceva competes with the chemotherapy agents Taxotere(R) (Sanofi-Aventis) and Alimta(R) (Eli Lilly and Company), both of which are indicated for the treatment of relapsed NSCLC. Astra Zeneca recently announced completion of enrollment in their Phase III study comparing ZactimaTM head-to-head with Tarceva in second-line NSCLC (ZEST). In September 2007, Astra Zeneca announced comparable survival data for Iressa(R) versus Taxotere(R) for the treatment of relapsed NSCLC in an international study. The results of this study have not yet been published, and it is unclear whether a re-filing of Iressa(R) with U.S. regulatory authorities is pending. Eli Lilly recently announced positive Phase III maintenance therapy data for Alimta(R). Since Alimta(R) has not yet been approved in this setting, its potential impact on treatment is uncertain. BMS/ImClone/Merck KGaA announced positive data on the use of Erbitux(R) in combination with chemotherapy for the front-line treatment of NSCLC (an unapproved use of Tarceva). This may have a material impact on the landscape of treatment options for the management of patients with relapsed NSCLC. In front-line pancreatic cancer, Tarceva primarily competes with Gemzar(R) (Eli Lilly) monotherapy and Gemzar(R) in combination with other chemotherapeutic agents. Tarceva also faces competition in the future from products in late-phase development, such as Erbitux(R), in the treatment of relapsed NSCLC and Xeloda(R) (Roche), in the treatment of pancreactic cancer; none of these products currently has regulatory approval for use in NSCLC or pancreatic cancer.●Nutropin (somatropin [rDNA origin] for injection) and Nutropin AQ growth hormone products approved for the treatment of growth hormone deficiency in children and adults, growth failure associated with chronic renal insufficiency prior to kidney transplantation, short stature associated with Turner syndrome, and long-term treatment of idiopathic short stature. 【2007】
Combined net U.S. sales of our Nutropin products decreased 2% to $371 million in 2007 and increased 2% to $378 million in 2006. Sales in 2007 and 2006 were positively affected by price increases in 2005 through 2007.
However, decreases in sales volume resulting from increased managed care contracting and increased competitive activity offset the price increase in 2007 and partially offset the price increase in 2006.【2007競合】
Nutropin faces competition in the growth hormone market from five (5) branded competitors: . Humatrope(R) (Lilly) . Genotropin(R) (Pfizer) . Norditropin(R) (Novo Nordisk) . Saizen(R) (Merck Serono) . Tev-Tropin(R) (Teva) Nutropin also faces competition from three (3) follow-on biologics: . Omnitrope(R) (Sandoz) . Valtropin(R) (LG Life Sciences) . Accretropin(R) (Cangene)●Activase (alteplase, recombinant) a tissue plasminogen activator (t-PA) approved for the treatment of acute myocardial infarction (heart attack), acute ischemic stroke (blood clots in the brain) within three hours of the onset of symptoms, and acute massive pulmonary embolism (blood clots in the lungs). 【2007】
Combined net U.S. sales of our three thrombolytics products .Activase, Cathflo Activase, and TNKase .
increased 10% to $268 million in 2007 and 11% to $243 million in 2006. Sales growth in 2007 and 2006 was due to growth in Cathflo Activase sales in the catheter clearance market and increased Activase sales in the acute ischemic stroke market. Also contributing to the increases in product sales for 2007 and 2006 were price increases in 2005 through 2007.【2007競合】
Thrombolytics: Our thrombolytic products face competition in the acute myocardial infarction market, with sales of TNKase and Activase affected by the adoption by physicians of mechanical reperfusion strategies. We expect that the use of mechanical reperfusion, in lieu of thrombolytic therapy for the treatment of acute myocardial infarction, will continue to grow. TNKase, for acute myocardial infarction, also faces competition from Retavase(R) (PDL BioPharma Inc.).●TNKase (tenecteplase) a modified form of t-PA approved for the treatment of acute myocardial infarction (heart attack). 【2007】 ●Cathflo Activase (alteplase, recombinant) a t-PA approved in adult and pediatric patients for the restoration of function to central venous access devices that have become occluded due to a blood clot. 【2007】 ●Pulmozyme (dornase alfa, recombinant) an inhalation solution of deoxyribonuclease I, approved for the treatment of cystic fibrosis. 【2007】
Net U.S. sales of Pulmozyme increased 12% to $223 million in 2007 and 7% to $199 million in 2006. The sales growth in both 2007 and 2006 reflects price increases in 2005 through 2007, as well as a focus on earlier, more aggressive treatment of cystic fibrosis.【2007競合】
Pulmozyme currently faces competition from the use of hypertonic saline, an inexpensive approach to clearing sputum from the lungs of cystic fibrosis patients. Approximately 25% of cystic fibrosis patients receive hypertonic saline and it is estimated that in a small percentage of patients (less than 5%), this use will impact how a physician may prescribe or a patient may use Pulmozyme.●Raptiva (efalizumab) a humanized anti-CD11a antibody approved for the treatment of chronic moderate-tosevere plaque psoriasis in adults age 18 or older who are candidates for systemic therapy or phototherapy. 【2007】
Net U.S. sales of Raptiva increased 19% to $107 million in 2007 and 14% to $90 million in 2006. The majority of growth in 2007 and 2006 was due to price increases in 2005 through 2007 and more favorable sales allowance in 2007.【2007競合】
Raptiva competes with established therapies for moderate-to-severe psoriasis, including oral systemics such as methotrexate and cyclosporin as well as ultraviolet light therapies. In addition, Raptiva competes with biologic agents Amevive(R) (Astellas), Enbrel(R) (Amgen), and Remicade(R) (Centocor). Raptiva also competes with the biologic agent Humira(R) (Abbott), which was approved by the FDA for use in moderate-to-severe psoriasis on January 18, 2008, and was used off-label in psoriasis prior to FDA approval. Raptiva may face future competition from the biologic Ustekinumab/CNTO-1275 (Centocor), which was filed with the FDA for approval in the treatment of psoriasis on December 4, 2007.● 【2007】
●Roche Diagnostics -http://www.roche-diagnostics.com/; Switzerland Roche Diagnostics is a division of F. Hoffmann-La Roche Ltd, Basel, Switzerland. ●Products & Services ●[Press Lounge] Press Releases
●ロシュ・ダイアグノスティックス株式会社 -http://www.rochediagnostics.jp/ 売上高358億円;従業員数730人(2005年2月現在) ●製品情報 ★研究用試薬・機器 ★生化学・免疫・血液凝固検査 ★POC検査 ★血糖自己測定システム ★遺伝子診断[PCR] 世界シェア70%のPCR遺伝子検査 その世界的な遺伝子診断[PCR]技術を生かした、遺伝子検出による臨床検査製品群 性感染症関連 肝炎関連 結核関連 PCR検査用自動測定装置 TaqMan PCR 自動測定装置 ●プレスリリース ●企業情報
■Salix Pharmaceuticals, Inc
- http://www.salix.com/index.aspx ; NASDAQ; 米国Raleigh, North Carolina 消化器官用薬専門メーカー; ・2002.7 we acquired the exclusive development rights in the United States to a granulated mesalamine product from Dr. Falk Pharma GmbH, ・2003.11 we acquired from aaiPharma LLC the exclusive right to sell 25, 75 and 100 milligram dosage strengths of azathioprine tablets in North America under the brand name Azasan. ・2004.6 we acquired the exclusive right to sell Anusol-HC 2.5% (hydrocortisone USP) cream, Anusol-HC 25 mg (hydrocortisone acetate) rectal suppositories, Proctocort 1% (hydrocortisone USP) cream and Proctocort 30 mg (hydrocortisone acetate) rectal suppositories from King Pharmaceuticals, Inc. ・2005.9 InKine Pharmaceutical Company, Inc.を買収。 $210.0 million. ・2005.9 we acquired Visicol with the completion of the acquisition of InKine Pharmaceutical Company, Inc. Visicol tablets are indicated for cleansing of the colon as a preparation for colonoscopy in adults 18 years of age or older. Visicol was the first, and it and OsmoPrep are the only, tablet bowel cleansing products approved by the FDA and marketed in the United States. OsmoPrep is a patented, second-generation tablet bowel cleansing product approved by the FDA in March 2006. ・2005.12 we acquired exclusive rights to sell MoviPrep in the United States from Norgine B.V. MoviPrep is a patent-protected, liquid PEG bowel cleansing product that was approved by the FDA in August 2006. ・2006.9 we acquired exclusive marketing rights for Sanvar(R) from Debiovision Inc. and paid an up-front payment of $0.5 million. Sanvar is currently undergoing a confirmatory Phase III trial for the treatment of acute esophageal variceal bleeding secondary to portal hypertension. ・2007.02 We added Pepcid(R) Oral Suspension and Diuril(R) Oral Suspension to our line of products by acquiring the U.S. rights to both products from Merck & Co., Inc. ●決算[12月]●製品売上高
($000) 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 収入 製品売上 232,890 178,766 232,880 208,533 154,703 101,697 55,807 33,456 14,129 6,307 491 契約収入他 - - 2,912 - 200 3,799 - - 8,221 8,235 2,602 総収入 232,890 178,766 235,792 208,533 154,903 105,496 55,807 33,456 22,350 14,542 3,093 研究開発費 89,466 76,630 71,947 47,917 34,547 20,366 23,654 17,967 6,629 3,844 4,787 営業利益 (40,106) (46,658) 11,852 30,334 (61,068) 6,649 (19,833) (25,832) (18,045) (3,174) (4,801) 純利益 (43,619) (47,037) 8,225 31,510 (60,585) 6,839 (20,101) (24,742) (17,498) (2,975) (4,611) 従業員数 395 280 270 240 215 150 132 - - - - *Colazalは2007.12.28のジェネリック３品出現により売上激減。
($000) 2009 2008 2007 2006 2005 2004 2003 2002 2001 備考 Xifaxan 117,939[51%] 79,928[45%] 64,260[28%] 51,600(+72)[25%] 30,051 9,821 - - - 2004.7発売[rifamixin]旅行者用下痢 Purgatives . Visicol/OsmoPrep/MoviPrep 76,287[33%] 62,862[35%] 47,693[20%] 45,502[22%] 5,137 - - - - うちVisicol 2,200 18,000 19,900 20,700 14,400 7,500 4,300 [sodium phosphate monobasic monohydrate, USP, sodium phosphate dibasic anhydrous, USP)]腸管洗浄剤 by InKineが2001発売 うちOsmoPrep 25,400 22,500 - - - - - [(sodium phosphate monobasic monohydrate, USP, and sodium phosphate dibasic anhydrous,USP) tablets;]腸管洗浄剤/米発売2006Q2 うちMoviprep 20,100 5,000 - - - - - [(PEG 350, sodium sulfate, sodium chloride, potassium chloride, sodium ascorbate and ascorbic acid) oral solution]腸管洗浄剤/米発売2006.10 Inflammatory Bowel Disease-Colazal/Aproso 5,782[2%] 10,545[6%] 92,401[40%] [] うちApriso 9,123[5%] - - - - - - - [顆粒mesalamine]潰瘍性大腸炎;米承認2008.10 うちColazal 1,422[1%] 92,401[40%] 103,500(-6)[49%] 110,250 85,434 55,807 33,456 14,129 2001.1発売(balsalazide disodium)潰瘍性大腸炎 Other 32,882[14%] 25,431[14%] 28,526[12%] 7,925[4%] 9,265
旧14,4026,442 - - - うちPepcid 22,191 - - - - - - [famotidine]潰瘍;Merck&Coから2007.2米販売権 うちAzasan 3,400 4,800 4,400 2,300 - - - [azathioprine]免疫抑制剤、重症関節リウマチ；;2003.11 aaiPharma LLCから北米独占権獲得;発売2004.2 うちAnusol-HC/Proctocort 2,900 3,000 4,800 4,100 [hydrocortisoneクリーム・坐剤]King Pharmaceuticals, Incから2004.6販売権 製品売上 232,890 178,766 232,880 208,533 154,703 101,697 55,807 33,456 14,129 [] ★Norgine B.V. [2006] In December 2005, we acquired the exclusive rights to sell NRL944 (now marketed by us under the trade name MoviPrep), a proprietary, liquid PEG bowel cleansing product in the United States from Norgine B.V. The agreement gives us the exclusive rights to develop and market the product in the United States. In return we will make upfront and milestone payments to Norgine that could total up to $37.0 million over the term of the agreement. As of December 31, 2006, $17.0 million of milestone payments had been made. The remaining milestone payments are contingent upon reaching sales thresholds. Because milestone payments are conditioned upon events that might never occur, the Company does not consider the potential milestone payments as purchase obligations nor a commitment to be reported in our contractual commitments table in its Management’s Discussion and Analysis of Financial Condition and Results of Operations. ★ALW Partnership [2006] In connection with Salix’s acquisition of InKine Pharmaceutical Company, Inc. in September 2005, Salix assumed a license agreement with ALW Partnership for the worldwide rights, in perpetuity, to develop, use, market, sell, manufacture, have manufactured and sub-license Visicol and improvements, including OsmoPrep, in the field of colonic purgatives, along with ALW Partnership’s body of proprietary technical information, trade secrets and related know-how. Pursuant to this license agreement, Salix pays to ALW, on a quarterly basis, a percentage royalty payment based on Salix’s net sales of these products. As the amounts of the royalty payments are based on net sales during a quarter Salix is unable to prospectively disclose the amount of such royalty payments. The agreement does provide a minimum annual royalty payment of $0.1 million. In December 2005, ALW sold the royalty stream to Clinical Development Capital. ★COMPETITION(2006) For example, many large, well capitalized companies already offer products in the United States and Europe that target the indications for balsalazide, including mesalamine and the granulated mesalamine product (GlaxoSmithKline plc, Giuliani S.p.A., Axcan Pharma, Inc., Solvay S.A., The Procter & Gamble Company and Shire Pharmaceuticals Group plc), sulfasalazine (Pharmacia & Upjohn, Inc.), and olsalazine (Pharmacia & Upjohn, Inc.). Asacol, marketed by Proctor & Gamble, is currently the most prescribed product for the treatment of ulcerative colitis in the United States, and Shire recently introduced once-a-day Lialda. Several prescription, liquid PEG products compete with Visicol, OsmoPrep and MoviPrep in the bowel cleansing market. These prescription products include Colyte, Golytely, Halflytely, and Nulytely (Braintree) and Trilyte (Schwarz Pharma). Generic prescription, liquid PEG products are also available. An over-the-counter product, Fleets Phospho-Soda also competes in the bowel cleansing market. The most frequently prescribed product for treatment of travelers’ diarrhea in the United States currently is ciprofloxacin, commonly known as “CiproR” and marketed by Bayer AG. The most frequently prescribed products that compete with Azasan are ImuranR, marketed by Prometheus Laboratories, Inc., and its various generics and PurinetholR, marketed by GATE Pharmaceuticals, and it’s various generics. The most frequently prescribed products that compete with Anusol-HC and Proctocort are AnaMantle HC, marketed by Bradley Pharmaceuticals; Analpram HC, marketed by Ferndale Laboratories; Proctofoam-HC and Proctocream-HC, marketed by Schwartz Pharma; Procto- Kit, marketed by Ranbaxy Pharmaceuticals; and various generics.
●Visicol(R) and OsmoPrep(R) (sodium phosphate monobasic monohydrate, USP, sodium phosphate dibasic anhydrous, USP) tablets 腸管洗浄剤 ・2005.9 InKine Pharmaceutical Company, Inc.を買収。 $210.0 million. ・2005.9 we acquired Visicol with the completion of the acquisition of InKine Pharmaceutical Company, Inc. Visicol tablets are indicated for cleansing of the colon as a preparation for colonoscopy in adults 18 years of age or older. Visicol was the first, and it and OsmoPrep are the only, tablet bowel cleansing products approved by the FDA and marketed in the United States. OsmoPrep is a patented, second-generation tablet bowel cleansing product approved by the FDA in March 2006. 【特許失効】Visicol 2013. OsmoPrep 2013. Additional patent protection is being sought on OsmoPrep that, if approved, will expire in 2024.
【2009】
In September 2005, we acquired Visicol with the completion of the acquisition of InKine Pharmaceutical Company, Inc. Visicol and OsmoPrep tablets are indicated for cleansing of the colon as a preparation for colonoscopy in adults 18 years of age or older. Visicol was the first, and it and OsmoPrep are the only, tablet bowel cleansing products approved by the FDA and marketed in the United States. OsmoPrep is a patented, second-generation tablet bowel cleansing product approved by the FDA in March 2006. OsmoPrep offers potential benefits compared to Visicol such as its lack of microcrystalline cellulose, smaller tablet size and possible lower dose administration.CDC, LLC, owns U.S. Patent No. 5,616,346, or the ‘346 patent, for the formulation and use of OsmoPrep, which CDC licensed to us for commercialization in the United States. The ‘346 patent is listed with the FDA as protecting our OsmoPrep product to 2013. In 2008, Novel Laboratories, Inc., filed an ANDA with the FDA seeking approval to market a generic version of OsmoPrep in the United States prior to the May 18, 2013 expiration of the ‘346 patent. On September 8, 2008, we filed a lawsuit in the United States District Court for the District of New Jersey against Novel for the infringement of the ‘346 patent and seeking a declaratory judgment confirming the validity of the patent. The lawsuit also joins CDC as a party. This lawsuit prevents Novel from marketing a generic version of OsmoPrep for up to 30 months, unless Novel receives an earlier non-appealable judgment to the contrary. On February 4, 2010 the Court conducted a patent claim construction, or Markman, hearing. No trial date has been set. An additional U.S. patent application for OsmoPrep is pending that, if issued, could provide patent protection through 2024.
On December 11, 2008, the FDA announced a proposed boxed warning for OsmoPrep and Visicol that addresses the potential risk of acute kidney injury. During 2009, working with the FDA, we revised the labels to include the boxed warning, and developed a risk evaluation and mitigation strategy, or REMS, including a medication guide. We plan to conduct postkｿmarketing clinical trials as part of this strategy.
【2007】
Approximately 5.2 million prescriptions for bowel cleansing products were written in 2007, representing a market value of $191 million. In terms of prescription dollar sales, the market for bowel cleansing products has been growing at a 28% annual compound rate for the last 5 years. Visicol and OsmoPrep compete with a number of liquid polyethylene glycol-salt (PEG-salt solution) bowel cleansing products and an over-the-counter oral sodium phosphate solution bowel cleansing product. Net product sales for Visicol were $14.4 million, $20.7 million, $19.9 million, $18.0 million and $2.2 million in 2003, 2004, 2005, 2006 and 2007, respectively. Net product sales for OsmoPrep were $22.5 million in 2006 and $25.4 million in 2007.【競合品】Several prescription, liquid PEG products compete with Visicol, OsmoPrep and MoviPrep in the bowel cleansing market. These prescription products include Colyte, Golytely, Halflytely, and Nulytely (Braintree) and Trilyte (Schwarz Pharma). Generic prescription, liquid PEG products are also available. An over-the-counter product, Fleets Phospho-Soda, also competes in the bowel cleansing market.
【2006】
VisicolR and OsmoPrep. (sodium phosphate monobasic monohydrate, USP, sodium phosphate dibasic anhydrous, USP) tablets. In September 2005, we acquired Visicol with the completion of the acquisition of InKine Pharmaceutical Company, Inc. Visicol tablets are indicated for cleansing of the colon as a preparation for colonoscopy in adults 18 years of age or older. Visicol was the first, and it and OsmoPrep are the only, tablet bowel cleansing products approved by the FDA and marketed in the United States. OsmoPrep is a patented, second-generation tablet bowel cleansing product approved by the FDA in March 2006. OsmoPrep tablets are indicated for cleansing of the colon as a preparation for colonoscopy in adults 18 years of age or older. OsmoPrep offers potential benefits compared to Visicol such as being microcrystalline cellulose-free, smaller tablet size and possible lower dose administration. The patent for the formulation and use of OsmoPrep expires in 2013. An additional U.S. patent application for OsmoPrep is pending that, if issued, could provide patent protection through 2024.Approximately 4.4 million prescriptions for bowel cleansing products were written in 2006, representing a market value of $148 million. In terms of prescription dollar sales, the market for bowel cleansing products has been growing at a 26% annual compound rate for the last 5 years. Visicol and OsmoPrep compete with a number of liquid polyethylene glycol-salt (PEG-salt solution) bowel cleansing products and an over-the-counter oral sodium phosphate solution bowel cleansing product.
●MoviPrep(R) (PEG 3350, sodium sulfate, sodium chloride, potassium chloride, sodium ascorbate and ascorbic acid) oral solution 腸管洗浄剤 ・2005.12 we acquired exclusive rights to sell MoviPrep in the United States from Norgine B.V.
MoviPrep is a patent-protected, liquid PEG bowel cleansing product that was approved by the FDA in August 2006. 【特許失効】The patent for MoviPrep will expire in 2024. In January 2007 the United States Patent Office issued a patent covering composition of matter and kit claims.【2009】
In December 2005, we acquired exclusive rights to sell MoviPrep in the United States from Norgine B.V. MoviPrep is a patent-protected, liquid polyethylene glycol-salt , or PEG, bowel cleansing product that was approved by the FDA in August 2006 and competes with a number of liquid PEG bowel cleansing products. MoviPrep is differentiated from other liquid PEG bowel cleansing products by the inclusion of ascorbic acid in its formulation. MoviPrep is indicated for bowel cleansing prior to colonoscopy, intestinal surgery and barium enema X-ray examinations.Norgine, B.V. and Norgine Europe, B. V. own U.S. Patent No. 7,169,381, or the ‘381 patent, which is listed with the FDA as protecting our MoviPrep product to September 2024. Norgine licensed MoviPrep and the ‘381 patent to us for commercialization in the United States. In 2008, Novel Laboratories, Inc., filed an Abbreviated New Drug Application, or ANDA, with the FDA seeking approval to market a generic version of MoviPrep in the United States prior to the September 1, 2024 expiration of the ‘381 patent. On May 14, 2008, we and Norgine filed a lawsuit in the United States District Court for the District of New Jersey against Novel for infringement of the ‘381 patent and seeking a declaratory judgment confirming the validity of the patent. This lawsuit prevents Novel from marketing a generic version of MoviPrep for up to 30 months, unless Novel receives an earlier non-appealable judgment to the contrary. Novel filed an Answer and Counterclaim on June 20, 2008. On June 25, 2009, we and Norgine amended the complaint to add a claim for correction of inventorship for the ‘381 patent. No trial date has been set. On February 9, 2010 U.S. Patent No. 7,658,914 was issued and listed in the Orange Book for MoviPrep.
【2007】
Net product sales for MoviPrep were $5.0 million in 2006 and $20.1 million in 2007.【2006】
MoviPrep(R) (PEG 350, sodium sulfate, sodium chloride, potassium chloride, sodium ascorbate and ascorbic acid) oral solution In December 2005, we acquired exclusive rights to sell MoviPrep in the United States from Norgine B.V. MoviPrep is a patent-protected, liquid PEG bowel cleansing product that was approved by the FDA in August 2006.
MoviPrep is differentiated from currently marketed, liquid PEG bowel cleansing products because it has ascorbic acid in its formulation. MoviPrep is indicated for bowel cleansing prior to colonoscopy, intestinal surgery and barium enema X-ray examinations. In January 2007 the United States Patent Office issued a patent providing coverage to September 1, 2024. Net product sales for MoviPrep were $5.0 million in 2006, despite not having launched it until October 2006.●Colazal(R) (balsalazide disodium) capsules 米国・欧州の競合品
the granulated mesalamine product (GlaxoSmithKline plc, Giuliani S.p.A., Axcan Pharma, Inc., Solvay S.A., The Procter & Gamble Company and Shire Pharmaceuticals Group plc), sulfasalazine (Pharmacia & Upjohn, Inc.), and olsalazine (Pharmacia &Upjohn, Inc.). Asacol, marketed by Proctor & Gamble, is currently the most prescribed product for the treatment of ulcerative colitis in the United States, and Shire recently introduced once-a-day Lialda. In addition, on December 28, 2007, the Office of Generic Drugs approved three generic balsalazide capsule products.In clinical trials, Colazal demonstrated at least comparable efficacy and had an improved safety profile as compared to some other oral 5-ASA products. Other 5-ASA products often do not deliver optimal doses of the active therapeutic agent to the colon. However, because Colazal’s proprietary formulation allows approximately 99% of the drug to reach the colon, it can work more quickly and effectively than comparable doses of other 5-ASA products that deliver less drug to the diseased area. In addition, some other 5-ASA products have historically been associated with side effects that cause up to 15-40% of patients to discontinue treatment.
The number of prescriptions written in 2002, 2003, 2004, 2005 and 2006 for Colazal was approximately 210,000, 314,000, 374,000, 399,000 and 440,000, respectively, making Colazal the fastest-growing oral 5-ASA product in the marketplace during that time period.★特許
The patents for the balsalazide composition of matter and method of treating ulcerative colitis with balsalazide expired in July 2001 in the United States; however, we were granted five years of new chemical entity data exclusivity for balsalazide until July 2005 and an extension of such patent under the Waxman-Hatch Act through July 2006. We also obtained patent extensions for the composition of balsalazide in Italy and the United Kingdom until July 2006. We have filed applications for patents for additional indications using balsalazide and related chemical substances.
【2009】
Our first drug, Colazal, was approved by the FDA in 2000 for the treatment of mildly to moderately active ulcerative colitis. We launched Colazal to physicians in the United States in January 2001 using our own sales force. In December 2006, the FDA approved Colazal for use in pediatric patients between 5 to 17 years of age with ulcerative colitis. The pediatric use of Colazal has been granted orphan drug designation. On December 28, 2007, the Office of Generic Drugs, or OGD, approved three generic balsalazide capsule products, and we announced that we had entered into an agreement with Watson Pharma, Inc. to market and sell an authorized generic of Colazal. We do not anticipate significant Colazal sales in 2010 or beyond.【2008】
Our first drug, Colazal, was approved by the FDA in 2000 for the treatment of mildly to moderately active ulcerative colitis. We launched Colazal to physicians in the United States in January 2001 using our own sales force. In December 2006, the FDA approved Colazal for use in pediatric patients between 5 to 17 years of age with ulcerative colitis. The pediatric use of Colazal has been granted orphan drug designation. On December 28, 2007, the Office of Generic Drugs, or OGD, approved three generic balsalazide capsule products, and we announced that we had entered into an agreement with Watson Pharma, Inc. to market and sell an authorized generic of Colazal.We had net product sales of $1.4 million, $92.4 million and $103.5 million of Colazal in the United States in 2008, 2007 and 2006, respectively. Colazal net product revenues for 2007 include a $34.6 million reduction representing our estimate of Colazal previously sold to wholesalers that may be returned to us under our return policy as a result of the generic approvals discussed above. We do not anticipate significant Colazal sales in 2009 or beyond.
DEVELOPMENT PROGRAMS
Balsalazide Disodium tablets
We have developed an 1100 mg tablet formulation of balsalazide disodium. We believe the convenience the balsalazide tablet formulation is designed to provide, by means of twice-a-day dosing and a reduced number of pills, demonstrates our ongoing commitment to bring products to market that better serve the needs of gastroenterologists and their patients. On July 17, 2007 we submitted an NDA to the FDA seeking approval to market an 1100 mg tablet formulation of balsalazide disodium. On May 16, 2008 we received an approvable letter from the FDA. We submitted a complete response to the approvable letter on June 30, 2008. On December 22, 2008, the FDA issued a complete response letter. Based on its review, the FDA has determined that the application cannot be approved in its present form and that clinical data from an additional adequate and well-controlled clinical trial will be required in order to conduct further review on the NDA. We have been granted a Type A meeting with the FDA and will meet with the FDA to discuss appropriate next steps and determine if the issues described in the December 22, 2008 complete response letter can be resolved and the product can be approved for marketing. We do not intend to conduct additional clinical investigation of balsalazide tablets in this indication. The patent for balsalazide disodium tablets will expire in 2018.
★特許
The patents for the balsalazide composition of matter and method of treating ulcerative colitis with balsalazide expired in July 2001 in the United States; however, we were granted five years of new chemical entity data exclusivity for balsalazide until July 2005 and an extension of such patent under the Waxman-Hatch Act through July 2006. We also obtained patent extensions for the composition of balsalazide in Italy and the United Kingdom until July 2006. We have filed applications for patents relating to additional indications using balsalazide and related chemical substances. In November of 2008, the United States Patent and Trademark Office issued a patent covering methods for increasing the bioavailability of balsalazide.
【2007】
2007.12.28 the Office of Generic Drugs(OGD)は３つのジェネリックを承認。 同日に当社はそのうちの１社Watson Pharma, Incと合意に達した。
We had net product sales of $55.8 million, $85.4 million, $110.3 million, $103.5 million and $92.4 million of Colazal in the United States in, 2003, 2004, 2005, 2006 and 2007 respectively. Colazal net product revenues for 2007 include a $34.6 million reduction representing our estimate of Colazal previously sold to wholesalers that may be returned to us under our return policy as a result of the generic approvals discussed above.【2006】
Ulcerative colitis is a chronic form of inflammatory bowel disease characterized by inflammation of the lining of the colon. Symptoms of active ulcerative colitis include rectal bleeding, abdominal pain, increased stool frequency, loss of appetite, fever and weight loss. The cause of ulcerative colitis is unknown and no known cure exists except for the removal of the colon. It is estimated that as many as 500,000 people in the United States have ulcerative colitis. People are most often diagnosed with the disease in their mid-30's, although the disease can occur at any age.In clinical trials, Colazal demonstrated at least comparable efficacy and had an improved safety profile as compared to some other oral 5-ASA products. Other 5-ASA products often do not deliver optimal doses of the active therapeutic agent to the colon. However, because Colazal’s proprietary formulation allows approximately 99% of the drug to reach the colon, it can work more quickly and effectively than comparable doses of other 5-ASA products that deliver less drug to the diseased area.
●Azasan(R) (azathioprine) tablets 【2009】
In November 2003, we acquired from aaiPharma LLC the exclusive right to sell 25, 75 and 100 milligram dosage strengths of azathioprine tablets in North America under the brand name Azasan. Azasan is an FDA-approved drug that suppresses immune system responses and is indicated for preventing rejection of kidney transplants and treatment of severe arthritis. In February 2004, we launched the 75 and 100 milligram dosage strengths of Azasan in the United States. The patents and data exclusivity for Azasan have expired.【2006】 ●Anusol-HC(R) and Proctocort(R) (hydrocortisone) creams and suppositories 【2009】
In June 2004, we acquired the exclusive right to sell Anusol-HC 2.5% (hydrocortisone USP) cream, Anusol-HC 25 mg (hydrocortisone acetate) rectal suppositories, Proctocort 1% (hydrocortisone USP) cream and Proctocort 30 mg (hydrocortisone acetate) rectal suppositories from King Pharmaceuticals, Inc. The two cream products are topical corticosteroids indicated for relief of the inflammatory and pruritic, or itching, manifestations of corticosteroidresponsive dermatoses. The two suppository products are indicated for use in inflamed hemorrhoids and postirradiation proctitis, as well as an adjunct in the treatment of chronic ulcerative colitis and other inflammatory conditions. The patents and data exclusivity for Anusol-HC and Proctocort have expired.【2007】
In June 2004, we acquired the exclusive right to sell Anusol-HC 2.5% (hydrocortisone USP) cream, Anusol-HC 25 mg (hydrocortisone acetate) rectal suppositories, Proctocort 1% (hydrocortisone USP) cream and Proctocort 30 mg (hydrocortisone acetate) rectal suppositories from King Pharmaceuticals, Inc. The two cream products are topical corticosteroids indicated for relief of the inflammatory and pruritic, or itching, manifestations of corticosteroidresponsive dermatoses. The two suppository products are indicated for use in inflamed hemorrhoids and postirradiation proctitis, as well as an adjunct in the treatment of chronic ulcerative colitis and other inflammatory conditions.
Combined net product sales for the Anusol-HC and Proctocort product lines were $4.1 million, $4.8 million, $3.0 million and $2.9 million in 2004, 2005, 2006 and 2007, respectively. The patents and data exclusivity for Anusol-HC and Proctocort have expired.【競合品】The most frequently prescribed products that compete with Anusol-HC and Proctocort are AnaMantle HC, marketed by Bradley Pharmaceuticals; Analpram HC, marketed by Ferndale Laboratories; Proctofoam-HC and Proctocream-HC, marketed by Schwartz Pharma; Procto-Kit, marketed by Ranbaxy Pharmaceuticals; and various generics.
【2006】 ●Pepcid(R) (famotidine) for Oral Suspension and Oral Suspension Diuril(R) (Chlorothiazide) 【2009】
In February 2007, we purchased the U.S. prescription pharmaceutical product rights to Pepcid Oral Suspension and Diuril Oral Suspension from Merck & Co., Inc. Pepcid Oral Suspension is a widely known prescription pharmaceutical product indicated for several gastrointestinal indications, including the treatment of duodenal ulcer, benign gastric ulcer and gastro-esophageal reflux disease. Pepcid Oral Suspension and Diuril Oral Suspension, both liquid formulations of their solid dosage form counterparts, compete in a combined annual U.S. market of approximately $183 million, concentrated in pediatric and hospitalized patient populations. The patents and data exclusivity for Pepcid Oral Suspension and Diuril Oral Suspension have expired.【2007】
In February 2007, we purchased the U.S. prescription pharmaceutical product rights to Pepcid Oral Suspension and Diuril Oral Suspension from Merck & Co., Inc. Pepcid Oral Suspension is a widely known prescription pharmaceutical product indicated for several gastrointestinal indications, including the treatment of duodenal ulcer, benign gastric ulcer and gastro-esophageal reflux disease. The acquisition reflects the ongoing execution of our strategy to expand and diversify revenue. Pepcid Oral Suspension and Diuril Oral Suspension, both liquid formulations of their solid dosage form counterparts, compete in a combined market of approximately $150 million that is concentrated in pediatric and hospitalized patient populations. Net product sales for Pepcid were $22.2 million in 2007.Net product sales for Diuril for 2007 were $0.2 million. The patents and data exclusivity for Pepcid Oral Suspension and Diuril Oral Suspension have expired.
【2006】 ●Xifaxan(Rifaximin) ★特許
The patents for the rifaximin composition of matter (also covering a process of making rifaximin and using rifaximin to treat gastrointestinal infectious diseases) expired in May 2001 in the United States and Canada. In May 2006, a U.S. patent (composition of matter and process patent that covers several physical states of rifaximin) was issued that we believe extends the patent coverage of the current form of rifaximin until May 22, 2024. Alfa Wasserman S.p.a., the patent owner, has licensed rights to rifaximin in the United States to Salix. In July 2006, Salix entered into an agreement with Cedars-Sinai Medical Center for the right to use its patent and patent application relating to methods of diagnosis and treating irritable bowel syndrome and other disorders caused by small intestinal bacterial over growth.
【2009】
Xifaxan is a gastrointestinal-specific oral antibiotic that the FDA approved in May 2004 for the treatment of patients 12 years of age and older with travelers’ diarrhea caused by noninvasive strains of E coli. According to the Centers for Disease Control, each year between 30% and 50% of international travelers, an estimated 20.0 million people, develop diarrhea, with approximately 80% of the cases caused by bacteria. Approximately 5.3 million people sought treatment in the United States for infectious diarrhea in 2009 and approximately 3.5 million of those patients were prescribed a drug.We believe the advantages of Xifaxan to treat these infections are two-fold: (1) site-targeted antibiotic delivery; and (2) improved tolerability compared to other treatments. Less than 0.4% of the drug is absorbed into the bloodstream when it is taken orally. In addition, the drug might also cause fewer side effects or discomforts such as nausea, headache or dizziness than observed with currently available, more highly-absorbed antibiotics. We believe Xifaxan is also less likely to cause harmful interaction with other drugs a patient may be taking. We believe Xifaxan is unique because there is no other U.S.-approved oral antibiotic with its potential lack of systemic absorption and safety profile.
We launched Xifaxan in the United States in July 2004 using our own direct sales force. We are exploring potential additional indications, formulations, clinical trials and co-promotion arrangements to capitalize on the potential for Xifaxan, including our development programs in hepatic encephalopathy, irritable bowel syndrome and prevention of travelers’ diarrhea. Based on these potential indications, we believe Xifaxan can potentially compete in an annual U.S. market in excess of approximately $9.5 billion, comprised of over 4 million patient visits. While the potential market for Xifaxan is large, we expect to capture only a portion of each market due to competition, ability to capture share in each market, market acceptance and/or other factors.
The patents for the rifaximin composition of matter (also covering a process of making rifaximin and using rifaximin to treat gastrointestinal infectious diseases) expired in May 2001 in the United States and Canada. Rifaximin is a new chemical entity and was granted a five-year new chemical exclusivity by the FDA when it was approved in May 2004. Rifaximin, therefore, had data exclusivity to May 2009. In May 2006, U.S. Patent No. 7,045,620 (the ‘620 patent, which is a composition of matter and process patent that covers several physical states of rifaximin) was issued. We believe this patent extends the protection of the current form of rifaximin until June 2024. In November 2009, U.S. Patent No. 7,612,199 (the ‘199 patent) issued and should provide protection until June 2024. This patent provides further protection relating to U.S. Patent No. 7,045,620 that covers several physical states, or polymorphous forms, of rifaximin and provides protection for all indications currently marketed and being assessed. Alfa Wasserman S.p.a., the owner of the ‘620 and the ‘199 patents, has licensed the rights to Salix in the United States. In July 2006, Salix entered into an agreement with Cedars-Sinai Medical Center, or CSMC, for the right to use its patent and patent applications relating to methods of diagnosis and treating irritable bowel syndrome and other disorders caused by small intestinal bacterial overgrowth. The CSMC agreement provides Salix the right to use U.S. Patent No. 7,452,857, which issued in November 2008, providing protection relating to rifaximin for treating irritable bowel syndrome, or IBS, caused by small intestinal bacterial overgrowth, and U.S. Patent No. 7,605,240, which issued in October 2009, providing protection relating to rifaximin for treating bloating caused by small intestinal bacterial overgrowth related to IBS, until August 2019. Below is a tabular summary of issued U.S. patents related to rifaximin that we own or have licensed.
* Licensed from Alfa Wasserman S.p.a.
U.S. Patent No. Issue Date Expiration
DateSubject 7,045,620* May 2006 June 2024 Composition of matter and process patent covering several physical states of rifaximin 7,452,857** November 2008 August 2019 Use of rifaximin for treating irritable bowel syndrome 7,605,240** October 2009 August 2019 Treatment of bloating caused by small intestinal bacterial overgrowth associated with irritable bowel syndrome 7,612,199* November 2009 June 2024 Covers several physical states, or polymorphous forms of rifaximin
** Licensed from Cedars-Sinai Medical CenterIn addition, we have filed applications for patents relating to additional indications using rifaximin and related chemical substances. In September 2009, Lupin Ltd. granted Salix the exclusive right in the United States to its bioadhesive drug delivery technology for use with rifaximin. In October 2009, Cipla, Limited granted Salix the exclusive rights in the United States to its amorphous rifaximin application PCT Patent Application No. PCT/GB2007/003629; WO 2008/035109.
★DEVELOPMENT PROGRAMS
We are committed to maximizing the commercial potential of our GI-targeted antibiotic, Xifaxan. We have prioritized our development efforts and have budgeted resources to expedite our late-stage trials in hepatic encephalopathy and irritable bowel syndrome. These studies are generating data that should provide the basis for forthcoming New Drug Applications.
Hepatic Encephalopathy
Hepatic encephalopathy, which encompasses a spectrum of reversible neuropsychiatric abnormalities that occur in patients with acute or chronic liver disease, is a serious medical condition that has no FDA-approved drug therapy available. In October 2008, we announced the successful completion and outcome of our pivotal Phase III trial to evaluate the efficacy, safety and tolerability of rifaximin in preventing hepatic encephalopathy, or HE. This study demonstrates that the protocolkｿspecified, intent-to-treat, primary endpoint comparison of a 6-month course of rifaximin at 550 mg dosed twice-a-day provides a highly statistically significant result in preventing HE, compared to placebo. This trial of 299 subjects demonstrated that rifaximin 550 mg dosed twice-a-day significantly reduced the risk of a breakthrough HE episode by 57.9% (p-value<0.0001) in cirrhotic patients with a history of two or more overt HE episodes within 12 months before study enrollment. The results seen with the primary endpoint are corroborated by the secondary endpoints. On June 24, 2009, we submitted an NDA for rifaximin tablets 550 mg for the maintenance of remission of hepatic encephalopathy. The FDA designated the NDA for Priority Review. A Priority Review classification is granted to drugs offering major advances in treatment, or providing a treatment where no adequate therapy exists. Based on this classification, the FDA issued an action date of December 24, 2009. In November 2009, the FDA informed the Company that they were extending the goal date by three months to provide time for a full review. The extended PDUFA action date is March 24, 2010. On February 23, 2010, the FDA convened a meeting of the Gastrointestinal Drugs Advisory Committee to discuss the efficacy and safety of the NDA for rifaximin in hepatic encephalopathy. The Gastrointestinal Drugs Advisory Committee recommended by a vote of 14 to 4 in favor of the approval of rifaximin 550mg dosed twice-a-day, for the maintenance of remission of hepatic encephalopathy.
Irritable Bowel Syndrome
Irritable bowel syndrome, characterized by abdominal pain, bloating and altered bowel habits, is one of the most common chronic medical conditions and is associated with substantial medical costs. In September 2009, we announced the successful completion and outcome of our two identical pivotal Phase III trials to evaluate the efficacy and safety of rifaximin 550 mg dosed three-a-day in the treatment of non-constipation irritable bowel syndrome (non-C IBS). In each trial rifaximin versus placebo treated patients demonstrated a statistically significant improvement for the primary endpoint of the adequate relief of IBS symptoms as assessed over a one-month period (weeks 3, 4, 5 and 6) following completion of a 14-day course of therapy (weeks 1 and 2). Consistent with the primary endpoint in each trial, the key secondary endpoint of relief of IBS-related bloating also demonstrated statistical significance of rifaximin versus placebo in each trial.
Prevention of Travelers’ Diarrhea
We have completed two Phase III trials to evaluate Xifaxan in the prevention of travelers’ diarrhea. In December 2008 we had a pre-NDA meeting with the FDA to discuss these data and potential next steps. During 2009 we decided to expedite the Company’s two highest priority clinical development programskｿrifaximin in the treatment of hepatic encephalopathy and irritable bowel syndrome. Consequently, further work on the prevention of travelers’ diarrhea has been suspended.
C. difficile-associated Diarrhea
In December 2008, we prematurely stopped patient enrollment (238 of the protocol-defined 300 patients) in our C. Difficile-associated diarrhea, or CDAD, trial and, therefore no longer consider this to be a Phase III trial. During 2009 we decided to expedite the Company’s two highest priority clinical development programskｿrifaximin in the treatment of hepatic encephalopathy and irritable bowel syndrome. Consequently, further work on C. difficileassociated diarrhea has been suspended.
●APRISO(TM)(mesalamine)extended-release capsules 0.375g - 潰瘍性大腸炎 【2009】
In July 2002 we acquired the exclusive development rights in the United States to a granulated mesalamine product from Dr. Falk Pharma GmbH, one of the most recognized gastroenterology companies worldwide. On October 31, 2008, the FDA granted marketing approval for Apriso for the maintenance of remission of ulcerative colitis in adults. Apriso is a locally-acting aminosalicylate and is the first and only mesalamine product approved by the FDA for once-a-day dosing for the maintenance of remission of ulcerative colitis. Apriso is designed to provide for the distribution of the active ingredient beginning in the small bowel and continuing throughout the colon. The product’s unique prolonged release mechanism might allow us to expand the range of treatment options for ulcerative colitis. We shipped Apriso to wholesalers in the fourth quarter of 2008 and launched Apriso to physicians in March 2009. Apriso is patent protected until 2018.【2008】In July 2002 we acquired the exclusive development rights in the United States to a granulated mesalamine product from Dr. Falk Pharma GmbH, one of the most recognized gastroenterology companies worldwide. On October 31, 2008, the FDA granted marketing approval for Apriso for the maintenance of remission of ulcerative colitis in adults. Apriso is a locally-acting aminosalicylate and is the first and only mesalamine product approved by the FDA for once-a-day dosing for the maintenance of remission of ulcerative colitis. Apriso is designed to provide for the distribution of the active ingredient beginning in the small bowel and continuing throughout the colon. The product's unique prolonged release mechanism might allow us to expand the range of treatment options for ulcerative colitis. We shipped Apriso to wholesalers in the fourth quarter of 2008 and launched Apriso to physicians in late February 2009. Ulcerative colitis is a chronic form of inflammatory bowel disease characterized by inflammation of the lining of the colon. Symptoms of active ulcerative colitis include rectal bleeding, abdominal pain, increased stool frequency, loss of appetite, fever and weight loss. The cause of ulcerative colitis is unknown and no known cure exists except for the removal of the colon. It is estimated that as many as 500,000 people in the United States have ulcerative colitis.
People are most often diagnosed with the disease in their mid-30's, although the disease can occur at any age.
Apriso is patent protected until 2018.
【2008 Dr. Falk Pharma GmbH】
Pursuant to Salix’s license agreement, as amended, with Dr. Falk Pharma GmbH, Salix acquired the rights to develop and market a granulated formulation of mesalamine. The agreement provides that Salix make milestone payments in an aggregate amount of up to $11.0 million to Dr. Falk upon certain events prior to the commercial launch of the product, and quarterly royalty payments thereafter. As of December 31, 2008, $9.0 million of milestone payments had been made. The remaining milestone payment is contingent upon achievement of additional regulatory approval. Because this milestone payments are conditioned upon events that might never occur, we do not consider the potential milestone payments as purchase obligations nor a commitment to be reported in our contractual commitments table in Management’s Discussion and Analysis of Financial Condition and Results of Operations. Royalties are only incurred if there is associated revenue, and then are included in “Cost of products sold” in the Statements of Operations.In March 2008 we acquired a license from Dr. Falk Pharma GmbH to a family of budesonide products, including a budesonide rectal foam and a budesonide gastro-resistant capsule, in the United States. The rectal foam product and the gastro-resistant capsule products have patent coverage in the U.S. until 2015 and 2016, respectively. The agreement requires Salix to make an upfront payment and regulatory milestone payments that could total up to $23.0 million to Dr. Falk Pharma, with the majority contingent upon achievement of U.S. regulatory approval. At such time as the use of either of these products is approved by the FDA, Salix will be required to pay Dr. Falk royalties on net sales of licensed products. As of December 31, 2008, $1.0 million of upfront and milestone payments had been made. The remaining milestone payments are contingent upon filing NDA's and achievement of regulatory approvals. Because these milestone payments are conditioned upon events that might never occur, we do not consider the potential milestone payments as purchase obligations nor a commitment to be reported in our contractual commitments table in Management's Discussion and Analysis of Financial Condition and Results of Operations.
【2008 COMPETITION】
For example, many large, well capitalized companies already offer products in the United States and Europe that target the indications for balsalazide and our mesalamine extended-release capsule product, including mesalamine (GlaxoSmithKline plc, Giuliani S.p.A., Axcan Pharma, Inc., Solvay S.A., The Procter & Gamble Company and Shire Pharmaceuticals Group plc), sulfasalazine (Pharmacia & Upjohn, Inc.), and olsalazine (Alaven Pharmaceutical LLC).Asacol, marketed by Proctor & Gamble, is currently the most prescribed product for the treatment of ulcerative colitis in the United States, and Shire introduced once-a-day Lialda in 2007. In addition, on December 28, 2007, the Office of Generic Drugs approved three generic balsalazide capsule products.
● 【2009】
●Salix Pharmaceuticals, Inc ■Investors ●Financial Reports - 年報、SEQ 2009 Form 10-K[pdf,91p] 2008 Form 10-K[pdf,93p] 2007 Form 10-K[pdf,83p] 2006 Form 10-K[pdf,77p] 2005 Form 10-K[pdf,71p] 2004 Form 10-K[pdf,55p] 2003 Form 10-K 2007 Annual Report 2006 Annual Report 2005 Annual Report 2004 Annual Report 2003 Annual Report ●News XIFAXAN® 550 mg Tablets Demonstrated Significant Acute And Sustained Relief Of Irritable Bowel Syndrome Without Constipation According To Findings Published In The New England Journal Of Medicine[2011.1.5]
XIFAXAN 550 Mg (Rifaximin) Demonstrates Acute And Sustained Relief Of Non-Constipation Irritable Bowel Syndrome Symptoms: Data Presented At The 2010 American College Of Gastroenterology (ACG) Annual Meeting[2010.10.18]
Salix Pharmaceuticals Announces Extension of XIFAXAN550 sNDA PDUFA Goal Date to March 7, 2011[2010.10.4]
Salix Announces FDA Acceptance For Filing And Priority Review Designation For Xifaxan550 sNDA For The Treatment Of Non-Constipation Irritable Bowel Syndrome[2010.8.9]
Salix Pharmaceuticals Announces NDA Submission For Xifaxan550 For Treatment Of Non-Constipation Irritable Bowel Syndrome[2010.6.8]
XIFAXAN® (Rifaximin) 550 mg Tablets Now Available In U.S. Pharmacies[2010.5.24]
Salix Announces Issuance Of U.S. Patent For Rifaximin[2010.5.20]
XIFAXAN 550 MG (Rifaximin) Demonstrated Acute And Sustained Relief Of NonkｿConstipation Irritable Bowel Syndrome Symptoms; Data From Target 1&2 Presented At Digestive Disease Week (DDW) [2010.5.3]
H.E.L.P. Is On The Way For Patients With Hepatic Encephalopathy (HE)[2010.4.27]
XIFAXAN® 550 Mg Tablets Demonstrate Significant Reduction Of Risk For Episodes Of Overt Hepatic Encephalopathy According To Findings Published In The New England Journal Of Medicine[2010.3.25]
FDA Approves XIFAXAN® 550 Mg Tablets For Reduction In Risk Of Overt Hepatic Encephalopathy (HE) Recurrence[2010.3.24]
FDA Advisory Committee Recommends Approval Of XIFAXAN® (Rifaximin) Tablets, 550 Mg For Maintenance Of Remission Of Hepatic Encephalopathy[2010.2.23]
Salix Pharmaceuticals Reports Concurrence with FDA on Content and Format of the Pending Rifaximin NDA in the Treatment of Non-Constipation Irritable Bowel Syndrome[2009.12.10]
Salix Pharmaceuticals Announces Statistically Significant Results for Both the Primary and Key Secondary Analyses of Rifaximin in the Treatment of NonkｿConstipation Irritable Bowel Syndrome in Two Phase 3 Trials (TARGET 1 and TARGET 2) [2009.9.14]
Salix Pharmaceuticals Announces FDA Acceptance for Filing and Priority Review Designation for Rifaximin NDA for the Maintenance of Remission of Hepatic Encephalopathy[2009.8.24]
Salix's Once-Daily APRISO Demonstrates Long?Term Safety in Patients for Maintenance of Remission from Ulcerative Colitis[2009.6.2]
APRISO(TM) Granted FDA Marketing Approval for Maintenance of Remission of Ulcerative Colitis[2008.10.31]
Data Released Today Demonstrate that Mesalamine Granules Maintain Remission in Ulcerative Colitis Patients Who Switch from Another 5-ASA[2008.10.7]
Salix Pharmaceuticals Announces Submission of Granulated Mesalamine New Drug Application[2007.12.31]
Salix Pharmaceuticals Announces Statistically Significant Top-Line Results for Second Product Registration Study of Granulated Mesalamine in Ulcerative Colitis[2007.10.7]
Salix Pharmaceuticals Announces Statistically Significant Top-Line Results of a Unique Granulated Mesalamine Product Registration Study in Ulcerative Colitis[2007.9.5]
Salix Pharmaceuticals Reports 4Q2008 and FY2008 Results[2009.3.10] Salix Pharmaceuticals Reports 4Q2006 And FY2006 Results[2007.2.28] COLAZAL(R) Pediatric Indication Approved [2006.12.20] COLAZAL(R) Pediatric Exclusivity Granted [2006.8.28] XIFAXAN(TM) Ships To Wholesale And Retail Customers[2004.7.13] - 発売2004.7.12; イタリアで1987年以来販売され(Alfa Wassermann S.p.A) 世界17か国で承認 FDA Grants Marketing Approval For Xifaxan(TM) (Rifaximin)
-- First Nonsystemic, Gastrointestinal Selective Antibiotic --[2004.5.26] Salix Receives FDA Notification That Rifaximin Amendment
Considered A Complete Response[2003.12.10] Salix Pharmaceuticals Submits Amendment For Rifaximin New Drug Application[2003.11.25] ●Products XIFAXAN (rifaximin), COLAZAL (balsalazide disodium) MoviPrep(PEG 3350, sodium sulfate, sodium chloride, potassium chloride, sodium ascorbate and ascorbic acid for oral solution) - 腸管洗浄剤; Low Volume Pres. High Volume Efficacy Osmoprep(sodium phosphate monobasic, USP, and sodium phosphate dibasic anhydrous, USP) Tablets. - 腸管洗浄剤; Reliable Tolerable Tablets Visicol(sodium phosphate monobasic monohydrate, USP, and sodium phosphate dibasic anhydrous, USP) Tablets. - 腸管洗浄剤; Tablets APRISO(TM)(mesalamine) - 潰瘍性大腸炎 Azasan(azathioprine) DIURIL®(chlorothiazide) Pepcid(famotidine) METOZOLV® ODT(metoclopramide HCl)
■Sanofi-Aventis
- http://en.sanofi-aventis.com/index.asp 合併して製薬世界第３位。 2004 Sanofi-SynthelaboがAventisを買収して、Sanofi-aventisが誕生。(Eur 47.8 bn ) * [Wikipedia]Sanofi-Synthelabo [Sanofi-Synthelabo] 1999 Sanofi-Synthelaboは、 Sanofi(仏石油企業Total S.A.子会社)とSynthelabo(L'Oreal子会社)と合併して誕生。 [Aventis] 1999 Aventisは、Rhone-Poulenc S.AがHoechst Marion Rousselと合併により誕生。 HMRはHoechst AGがRoussel Uclaf and Marion Merrell Dowとの合併により誕生した会社。 2004 Aventis Spaは、伊Gruppo Lepetitを買収。 ●会社決算*2004年度の数値：上段は2005年決算発表時2004 Pro forma；下段は2004年決算発表値 ●主要製品売上高
(Euro milllion) 2010 2009 2008 2007 2006 2005 2004 2003 純売上高 30,384(+3.7) 29,306(+6.3) 27,568(-1.7) 28,052 28,373 27,311 14,871
旧25,199
旧25,418(+4.6)24,296 営業利益 12,660[41.7%] 12,028[41.0%]
旧11,153(+14.2)4,394 5,911 4,828 2,888
旧4,7532,426
旧3,786
8,163(+12.5)7,254 経常利益 10,853(+14.3) 4,162 5,772 4,748 2,643 3,199
7,483(+15.9)6,456 純利益 9,215[30.3%] 8,629[29.4%]
旧8,471[28.9%]3,851[14.0%] 5,263[18.7%] 4,006 2,258 1,986
旧2,316
旧5,247(+17.9)4,451 研究開発費 4,401[14.5%] 4,583[15.6%] 4,575[16.6%] 4,537[16.2%] 4,430[15.6%] 4,044[14.8%] 3,961(-2.6) 4,066 従業員数 101,575 104,867 98,213 99,495 100,289 97,181 96,439 [S]33,686 仏 25,896[25.5%] 27,694[26.41%] 28,223[28.74%] 28,592[28.7%] 27,995[28.9%] 27,995[28.8%] 27,663[28.7%] 12,058[36.4%] 他の欧州 28,919[28.5%] 30,202[28.80%] 25,292[15.75%] 26,785[27.0%] 27,522[27.5%] 27,102[27.9%] 26,912[27.9%] 9,380[28.4%] 米国 12,954[12.7%] 14,517[13.84%] 15,228[15.50%] 15,921[16.0%] 16,196[16.1%] 16,471[16.9%] 15,811[16.3%] 4,162[12.6%] 日本 3,153[3.1%] 3,198[3.05%] 3,121[3.18%] 2,989[3.0%] 2,928[2.9%] 2,697[2.8%] 2,752[2.9%] その他 30,653[30.2%] 29,256[27.90%] 26,349[26.83%] 25,208[25.3%] 24,679[24.6%] 22,916[23.6%] 23,301[24.2%] 7,368[22.2%] ●地域別売上高 純売上高 30,384(+3.7) 29,306(+5.3) 27,568(-1.7) 28,052(-1.1) 28,373(+4.0)[100%] 27,311(+9.3) 24,984
25,418(+4.6)[100%]欧州 8,997(-8.8) 12,059(+3.2) 12,096(-0.7) 12,184(-0.3) 12,219(+1.1)[43.1%] 12,134(+8.2) 11,218
11,122(+5.9)[43%]米国 8,968(-8.4) 9,426(+2.8) 8,609(-9.1) 9,474(-0.5) 9,966(+3.9)[35.1%] 9,566(+11.5) 8,579
9,772(+16.1)[35%]その他 9,075(+16.3) 7,821(+12.1) 6,863(+7.3) 6,394(+3.3) 6,188(+10.5)[21.8%] 5,611(+8.2) 5,187
5,524(+9.2)[22%]日本 2,225(+9.1) 1,844(+10.7) ●事業別売上高 純売上高 30,384(+3.7) 29,306(+6.3) 27,568(-1.7) 28,052(-1.1) 28,373(+3.9) 27,311(+9.3) 24,984
25,418(+4.6)[100%]医薬 26,576(+2.9) 25,823(+4.5) 24,707(-2.2) 25,274(-2.2) 25,840(+2.3) 25,249(+9.1) 23,359
23,794[94%]人体用ワクチン 3,808(+9.3) 3,483(+21.7) 2,861(+3.0) 2,778(+9.8) 2,533(+22.8) 2,062(+26.9) 1,625
1,624[6%]from 20-F document 2004[2005.4.11,pdf,301p]～SEC Annual erport *冒頭[S]=旧Sanofi-Synthelabo,[A]=旧Aventis ※糖尿病 Lantus ランタス [2005]47.5%増Eur 1,214 millionとブロックバスター製品となった。 ピークがなく２４時間効果が持続する唯一のインスリンアナログ製剤として 2005.12時点で米国シェア30.4%。 ●ワクチン製品売上高
(Euro milllion) 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 備考 ★循環器 [A]Lovenox /Clexane 2,806(-10.5) 3,043(+11.1) 2,738(+4.8) 2,612(+7.3) 2,435(+13.6) 2,143(+13.8) 1833(+14.8) 1659(+21.3) 1563(+13.3) 1453[37.6] 1,042 782[33.3] 551[+42%] enoxaparin sodium;抗血栓 欧 782(+7.3) 890(+13.7) 815(+8.1) 756(+9.4) 689(+6.5) 647(+10.4) 米 1,439(-22.7) 1,822(+5.3) 1,625(+11.7) 1,579(+14.8) 1,502(+16.0) 1,287(+14.8) EmergingMarkets 499(+6.9) (+) (+) 他 86(+19.4) 331(+14.8) 298(+12.0) 277(+16.9) 244(+13.5) 209(+18.8) [S]Plavixプラヴィックス 2,083(-24.6) 2,623(+0.5) 2,616(+7.9) 2,424(+8.7) 2,229(+10.0) 2,026(+20.2) 1685(+27.8) 1325(+34.2) 987(+41.5) 705(+61) 437(+118) [clopidogrel]動脈血栓症治療薬 欧 641(-53.9) 1,512(-10.4) 1,732(+3.5) 1,704(+5.3) 1,617(+9.5) 1,480(+20.5) 米 213(-4.1) 222(+28.5) 172(+3.0) 167(+7.7) 156(-26.1) 210(+9.9) EmergingMarkets 648(+0.7) (+) (+) 他 581(+25.4) 889(+19.3) 712(+34.8) 553(+25.7) 456(+) 336(+26.3) Plavix/Iscover～S-A分 2,083(-24.6) 2,340 2,333 2,136 1,951 1,683 1,368 欧 641(-53.9) 1,443 1,622 1,583 1,485 1,344 1,107 米 213(-4.1) - - - 10 3 2 EmergingMarkets 648(+0.7) (+) (+) 他 581(+25.4) 897 711 553 456 336 259 Plavix/Iscover～BMS分 4,442 3,810 3,486 2,633 3,056 2,715 欧 161 211 225 230 240 235 米 4,026 3,351 2,988 2,157 2,582 2,287 EmergingMarkets (+) (+) 他 255 248 273 246 234 193 Plavix/Iscover～合算 6,895(-2.9) 6,782(+6.2) 6,143(+9.3) 5,622 4,584(-3.3) 4,739(+16.1) 4,083 欧 822(-49.2) 1,604(-10.3) 1,833(+1.4) 1,808 1,715(+8.3) 1,584(+18.0) 1,342 米 4,626(+10.8) 4,026(+12.8) 3,351(+12.1) 2,988 2,167(-16.2) 2,585(+12.9) 2,289 EmergingMarkets (+) (+) 他 1,447(+13.7) 1,152(+14.4) 959(+16.1) 826 702(+23.2) 570(+26.1) 452 (BMS等合算) 4108 3225 2587 2033 1279 [S]Aprovelアプロヴェル 1,327(+4.2) 1,236(+2.8) 1,202(+11.3) 1,080(+6.4) 1,015(+13.8) 892(+13.9) 783(+15.7) 683(+21.5) 562(+34) 423(+41) 300(+52) [irbesartan]降圧剤/Avapro 欧 825(-5.0) 916(+2.6) 910(+9.9) 838(+3.8) 808(+11.4) 1,480(+20.5) 米 39(+457.1) 7(-) - - - - EmergingMarkets 358(+8.3) (+) (+) 他 105(+67.3) 313(+8.6) 292(+29.8) 242(+21.0) 207(+21.1) 165(+13.0) Aprovel/Avapro/Karvea～S-A分 1,327(+4.2) 1,124 1,107 993 911 794 693 欧 825(-5.0) 810 816 750 704 629 552 米 39(+457.1) - - - - - - EmergingMarkets 358(+8.3) (+) (+) 他 105(+67.3) 314 291 243 207 165 141 Aprovel/Avapro/Karvea～BMS分 888 859 858 853 765 744 欧 172 176 172 174 160 162 米 524 499 507 516 458 455 EmergingMarkets (+) (+) 他 192 184 179 163 147 127 Aprovel/Avapro/Karvea～合算 2,056(-1.5) 2,012(+1.7) 1,966(+6.2) 1,851 1,764(+13.1) 1,559(+8.5) 1,437 欧 947(-4.4) 982(+0.8) 992(+76) 922 878(+11.3) 789(+10.5) 714 米 482(-10.4) 524(-1.6) 499(-1.6) 507 516(+12.7) 458(+0.7) 455 EmergingMarkets (+) (+) 他 627(+13.5) 506(+7.2) 475(+12.6) 422 370(+18.6) 312(+16.4) 268 (BMS等合算) 1449 1255 1068 924 665 [A]Delix /Tritace 410(-7.2) 429(-12.6) 513(-30.8) 741(-24.2) 977(-3.2) 1,009(+2.4) 985(-8.8) 1066(+20.6) 923(+34.2) 709[36.8] 530 370[43%] 363 [+2] ramipril;高血圧 欧 189(-4.1) 298(-8.2) 358(-29.4) 466(-8.8) 509(-11.5) 576(-0.7) 米 0 - - 1(-92.9) 16(+100.0) 8(-38.5) EmergingMarkets 191(-2.6) (+) (+) 他 30(-41.9) 131(-11.3) 155(-31.4) 274(-37.4) 452(+2.0) 425(+8.4) Multaq 172(+560.0) 25(-) - [dronedarone]抗不整脈薬 欧 39 - (+) (+) 米 128 25(-) - (+) (+) EmergingMarkets 2 (+) (+) 他 3 - (+) (+) [S]Fraxiparineフラキシパリン - - - - - - - 319(-1.5) 324(+10.1) 294(+17) 255(+8) [nadroparin calcium)]血栓症治療薬 [S]Ticlidチクリッド - - - - - - - - 137(-33.2) 205(-13) 235(-11) [ticlopidine]血栓症治療剤 [S]Corotropeコロトロープ - - - - - - 127(-43.5) 226(+31) 180(+7) [milrinone]急性心不全治療薬/Primacor [S]Cordaroneコルダロン - - - - - - - 146(-9.9) 162(+3.1) 157(+4) 156(+11) [amiodarone]不整脈治療薬 [S]Tildiemティルジエム - - - - - - - 131(-7.1) 141(-6.9) 151(-2) 154(-4) [diltiazem]狭心症・高血圧治療薬 [S]Kerloneケルロン - - - - - - - - 77(-5.0) 82(+8) 77(-11) [Betaxolol]高血圧・狭心症治療薬 [A][Thrombo./Cardio] - - - - - ? 3521(+12.2) 3435(+8.2) 3325 ★神経系 [S]Stilnoxスティルノックス/Ambien CR 819(-10.9) 873(+6.2) 829(-33.7) 1,250(-38.3) 2,026(+33.4) 1,519(+10.6) 1373(+5.8) 1345(-5.5) 1424(+25.5) 786(+35) 582(+32%) [zolpidem]睡眠導入剤/Ambien/Myslee 欧 55(-8.3) 72(-3.9) 82(-4.7) 85(-11.5) 95(-12.0) 108(-9.2) 米 443(-21.6) 555(-4.8) 547(-44.9) 1,093(-35.0) 1,838(+38.1) 1,331(+12.6) EmergingMarkets 68(+5.0) (+) (+) 他 253(+13.6) 246(+9.1) 200(+11.1) 72(-20.0) 93(+14.8) 80(+11.1) (BMS等合算) 1461 ? 1455 1215 920 [S]Depakineデパケン 372(+7.6) 329(+2.2) 329(+4.1) 316(+5.0) 301(-5.3) 318(+4.6) 304(+9.4) 277(+3.7) 267(+11) 240(+15) 211(+9) [valproate de sodium]抗てんかん剤 欧 148(+2.1) 204(+2.8) 219(+3.3) 216(+2.4) 210(-10.3) 235(+4.0) 米 0 - - - - - EmergingMarkets 209(+12.0) (+) (+) 他 15(+9.1) 125(+15.7) 110(+17.0) 100(+13.6) 91(+8.3) 83(+6.4) [A]Copaxone 513(+8.4) 467(-24.9) 622(-47.2) 1,177(+10.1) 1,069(+18.5) 902(+24.1) 727(+20.3) 617(+27.3) 554(+51.5) 383[51.5] (1)246 138[79%] 74[+87%] glatiramer acetate /多発性硬化症/欧州はTevaと共同販売 欧 482(+9.1) 454(+20.7) 381(+18.3) 324(+16.1) 279(+20.8) 231(+24.9) 米 0 0(-100) 210(+19.3) 801(+19.4) 733(+17.5) 622(+24.9)(+) EmergingMarkets 13(-13.3) (+) (+) 他 18(+7.7) 13(-54.8) 31(+40.9) 52(-5.5) 57(+9.6) 49(+11.4) [S]Dogmatilドグマチール - - - - - - - ? 78(-79) 86(-9.0) 134(-4) [sulpiride]精神障害治療薬 [S]Aspegicアスペジック - - - - - - - ? 108(-6.7) 101(+0) 100(+1) [aspirin lysin]解熱・鎮痛剤 [S]Solianソリアン - - - - - - - 148(+9.6) 135(+17.2) 115(+24) 93(+22) [amisulpride]精神分裂症治療薬 [A][CentrNervSystem] - - - - - - 1521(+8.9) 1530(+11.6) 1448 ★癌 [A]Taxotere 2,122(-6.4) 2,177(+7.1) 2,033(+8.5) 1,874(+7.0) 1,752(+8.9) 1,609(+12.8) 1426(+5.4) 1362(+22.5) 1261(+32.7) 1003[34.8] 744 500[48.9] 342[+46%] [doxetaxel] 肺癌、乳癌、前立腺癌 欧 709(-10.6) 928(+7.1) 900(+10.8) 819(+14.5) 714(+14.2) 628(+20.1) 米 786(-8.0) 827(+5.3) 737(+15.9) 691(+6.5) 708(+1.0) 695(+7.3) EmergingMarkets 394(+1.4) (+) (+) 他 233(+2.5) 422(+5.1) 396(+13.8) 364(+17.0) 330(+13.8) 286(+12.2) [S]Eloxatineエロキサチン 427(-58.8) 957(-28.8) 1,348(-11.4) 1,521(-10.2) 1,693(+8.2) 1,564(+30.6) 1198(+48.1) 824(+111.8) 389(+101) 194(+39) 141(+76) [oxaliplatine]抗大腸がん薬 欧 46(-42.9) 98(-52.4) 214(-42.6) 374(-33.7) 564(+3.7) 544(+31.4) 米 172(-76.4) 677(-37.2) 948(+6.2) 971(+9.8) 965(+7.3) 895(+28.0) EmergingMarkets 150(-9.8) (+) (+) 他 59(+4.0) 182(-1.6) 186(+13.4) 176(+11.4) 164(+29.1) 125(+47.1) JEVTANA 82(-) [cabazitaxel]進行性前立腺がん;FDA承認2010.6.17、EU承認2011.3.20 欧 - (+) (+) 米 82(-) (+) (+) 他 - (+) (+) [A][Oncology癌] - - - - - 1835(+16.9) 1743(+22.6) 1494 [A]Campto - - - - - - - 264(+12.9) 241(+21.3) 202[36.4] 151 90[68%] 48[+88%] irinotecan:大腸癌/ヤクルトから導入 ★泌尿器 [S]Xatralザトラル 296(-3.4) 296(-7.2) 331(-0.6) 333(-5.7) 353(+7.6) 328(+18.8) 276(+26.6) 222(+22.0) 182(+24.3) 147(+23) 120(+11) [alfuzosine]前立腺肥大治療薬 欧 66(-14.3) 93(-28.9) 148(-10.3) 167(-20.5) 210(-10.3) 234(+6.8) 米 155(+2.7) 147(+16.0) 119(+20.2) 107(+25.9) 92(+73.6) 53(+120.8) EmergingMarkets 70(+0.0) (+) (+) 他 5(-50.0) 56(-10.8) 64(+14.3) 59(+22.9) 51(+21.4) 41(+20.6) ★呼吸器・アレルギー [A][Respir.&Allergy] - - - - - 2317(-3.1) 2794(+14.8) 2575 [A]Allegra /Telfast 607(-22.4) 731(+9.8) 688(-2.5) 706(+2.6) 688(-48.8) 1,345(-10.5) 1,503(-13.5) 1736(+1.1) 2030(+22.1) 1762[48.9] 1,166 729[59.8] 436[+67%] fexofenadine 欧 16(-5.9) 23(-20.0) 39(-25.0) 54(+3.8) 51(-1.9) 52(-10.3) 米 147(-63.6) 306(-15.9) 333(-0.9) 369(+4.8) 384(-62.7) 1,001(-15.0) EmergingMarkets 88(+17.4) (+) (+) 他 356(-3.2) 402(+13.9) 316(+10.5) 283(+21.5) 253(-11.2) 292(+19.7) [A]Nasacort 189(-16.8) 220(-8.3) 241(-18.0) 294(+3.9) 283(+1.8) 278(-3.1) 287(+3.2) 278(-0.7) 329(+31.2) 266[28.8] 204 165[24%] 127[+29%] triamcinolone acetonide 欧 28(-3.4) 36(-2.6) 39(-9.3) 44(+10.0) 41(+7.9) 38(+2.7) 米 130(-20.3) 158(-15.4) 175(-13.8) 222(+13.3) 214(-0.5) 212(-3.2) EmergingMarkets 26(-10.7) (+) (+) 他 5(-20.0) 26(+0) 27(-3.6) 28(+3.7) 28(+0.0) 28(-) ★リウマチ・骨粗鬆症 [A][Arthrit/Osteo] - - - - - 812(+14.4) 799(+26.0) 677 [A]Arava - - - - - - - 255(8.3) 271(+10.7) 258[31.8] 192 107[80.1] 19[>400] [leflunomide]リウマチ [A]Actonel 238(-16.3) 264(-20.0) 330(+3.1) 320(-8.8) 351(-3.6) 364(+19.3) 305(+57.2) 194(+81.4) 117 309 63 - - [riserdronate];米国除く;日本売上含む;Osteoporosis,Paget's disease 欧 104(-23.5) 162(-25.0) 220(+8.9) 204(-16.0) 242(+3.4) 235(+22.4) 米 0 - - - - - EmergingMarkets 93(-12.4) (+) (+) 他 41(+3.2) 102(-2.7) 110(+2.8) 116(+10.5) 109(+14.7) 129(+26.5) ★抗感染薬 [A][Anti-Infectives] - - - - - 1368(-8.4) 1560(+5.4) 1546 [A]Targocid - - - - - - - 207(-1.1) 222(+18.2) 199[12.6] 190 173[10%] 137[+27%] Teicoplanin [A]Tavanic - - - - - - - 216(-12.3) 257(+38.9) 192[48.8] 137 80[72%] 28[>100] levofloxacin [A]Ketek - - - - - - - 115(+135.2) 52 3 -- --- ---- telithromycin [A]Synercid - - - - - - - ? ? 33[-25.6] 44 15[196] - quinupristin/dalfopristin (2002.12.31King Pharmへ移管) *(2002)$78 millionはDatamonitor調べ ★代謝系薬 [A][Metabol/Diabete] - - - - - 1977(+11.3) 1978(+18.6) 1761 [A]Amaryl 478(+7.7) 416(+9.8) 387(-1.3) 392(-13.1) 451(-33.4) 677(-0.0) 677(+14.8) 596(+14.8) 578(+28.6) 478[29.6] 377 242[55.8] 146[+66%] glimepiride 欧 42(-17.6) 83(-6.4) 100(-15.3) 116(-33.7) 174(-31.5) 255(+5.8) 米 6(-33.3) 9(+33.3) 6(-285.0) 9(-35.7) 15(-91.9) 181(-13.4) EmergingMarkets 222(+21.7) (+) (+) 他 208(+3.3) 324(+7.2) 281(+5.6) 267(+9.4) 262(+10.1) 241(+8.6) [A]Insuman 133(+1.5) - - - - - - 176(+4.5) 172(+4.2) 170[8.9] 156 98[59%] - human insulin [A]Lantus 3,510(+9.1) 3,080(+25.7) 2,450(+20.6) 2,031(+21.9) 1,666(+37.2) 1,214(+45.9) 832(+73.1) 487(+87.1) 299(+NA) 94[NA] 10 - - insulin glargine 欧 684(+5.3) 767(+12.2) 713(+16.3) 627(+20.6) 520(+26.5) 413(+40.5) 米 2,134(+7.4) 1,909(+23.6) 1,452(+30.8) 1,200(+30.3) 1,006(+39.7) 717(+46.6) EmergingMarkets 508(+18.2) (+) (+) 他 184(+258.2) 404(+42.8) 285(+46.2) 204(+52.2) 140(+62.8) 84(+110.0) Apidra 177(+24.1) 137(+39.8) [insulin glulisine [rDNA origin]]速効型インスリン 欧 68(+21.8) 68(+40.0) (+) (+) 米 62(+11.1) 54(+27.5) (+) (+) EmergingMarkets 35(+37.5) (+) (+) 他 12(+150.0) 15(+87.5) (+) (+) ★その他 [A][その他] - - - - - 1838(-8.6) 2187 [A]Rilutek - - - - - - ? ? 118[13.9] 106 80[31%] 61[+30%] riluzole [A]Refludan - - - - - - - ? ? ? 14 9[+43%] lepirudin Flagship製品 13,278(+6.4) 15品目 計 16,657(-2.4) 17,071(-1.3) 17,289(+6.8) 16,188(+13.6) 14,247 12,794 その他 計 6,064(-1.9) 6,078(-6.3) 8,050(-1.9) 8,203(-4.1) 8,551(-5.6) 9,061(-2.9) 9,328 9,902 消費者保健製品 2,217(+45.7) 1,430(+18.9) ジェネリック 1,534(+41.5) 1,012(+185.9) 医薬品 合計 26,576(-1.6) 25,832(+4.5) 24,707(-2.2) 25,274(-2.2) 25,840(+2.3) 25,249(+7.1) 23,575 22,696 [S] 連結売上 ? 8048(+8.1) 7448 [A] 合計 - 16791(+5.9) 17591 [A] 処方薬 計 - 15190(+4.9) 16026 [A] 戦略製品 - 9230(17.1) 8868 Myslee(マイスリー)[アステラス製薬]単独売上高 98 欧 (+) (+) 米 (+) (+) EmergingMarkets (+) (+) 他 (+) (+) from Aventis Reports Full-Year Results for 2003[2004.2.5] - income statements / sales figures[付表,xls]製品別売上等
(Euro milllion) 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 備考 ★ワクチン [A][Vaccines] 2,861(+3.0) 2,778(+9.7) 2,533 2,062(+26.9) 1624(+1) 1601(+16.6) 1580 [A]Vaccin-小児混合 768(+16.4) 660(+4.3) 633 - 336(-3.4) 527(+16.2) 495(+21.1) 422 [A]Vaccin-Polio - - - - - 184(-22.0) 236(-7.9) 304(+11.9) 284[9.3] 217 [A]Vaccin-Flu 1,297(+18.7) 1,062(+46.7) 736(-3.9) 766(-8.3) 835(+27.5) 655(+28.6) 522(+25.4) 418(17.7) 458(+1.5) 473[94.0] 240 [A]Vaccin-旅行検疫 382(+15.7) 313(+0) 309(-5.5) 327(+15.1) 284
旧239(+34.3)178(+3.6) 170 158(2.4) 221(-3.0) 235 [A]Vaccin-meningitis - - - - 86(+6.2) 81(5.0) 103(+8.5) 98 [A]Vaccin-meningitis/Pneumonia 527(-6.7) 538(+6.1) 472(-2.1) 482(+55.5) 310(+22.0) 254(+137.0) 108 [A]Adult Boosters 449(+4.7) 406(-3.0) 399(-0.7) 402(+19.3) 337(+23.4) 273(+58.8) 170(+21.7) 143(+28.5) 172(+60.1) 111 [A]Vaccin-HIB - - - - - ? ? 378[1.4%] 370 &,Acellular pert [A]Vaccin-Hepatitis - - - - - ? ? 74[-36.8] 118 [A]Vaccin-HIB/Polio/Whooping Cough - 660(+4.3) 633(+18.5) 534(+3.2) 506 [A]Vaccin-HIB/Polio/Pertussis 984(-2.9) その他 169(-18.4) 196(+6.8) 177(+25.5) 141(+5.2) 134
旧179(+5.3)170(+12.1) 149 216 ワクチン 合計 3,808(+9.3) 3,483(+19.2) 2,861(+3.0) 2,778(+9.7) 2,533(+22.7) 2,064(+26.9) 1625(+1) 1601(+16.6) 1580 Menactra 445(+1.1) 404(+7.9) 415(+96.1) Adacel 267(-1.2) 255(+20.0) 234(+64.5) Pentacel 343 84(-) [DTP,Polio&HIVの初の5種小児ワクチン]米発売2008.7 Gardasil 263(-33.5)
●人体用ワクチン 【2009】
通年の純売上高は、インフルエンザA 型（H1N1）ワクチンの出荷に加え、Pentacel®の好業績に牽引され、19.2%増の34 億8,300 万ユーロとなりました。ヒト用ワクチン事業は、2009 年度通年におけるグループの純売上高合計の11.9%（前年同期は10.4%）を占めました。【2008】
ヒト用ワクチン事業の連結純売上高は、第4 四半期に8.9%増の7 億900 万ユーロ、通年に9.6%増の28 億6,100 万ユーロとなりました。米国では、通年の純売上高が9.7%増の16 億8,300 万ユーロとなりました。【2007】 【2006】
We are a major player in the vaccines industry, with net sales of Eur2,533 million in 2006; and with leading vaccines in five areas:
・Pediatric combination vaccines providing protection against diseases such as pertussis, diphtheria, tetanus, and Haemophilus influenzae type b infections. Our main products are Daptacel(R), Tripedia(R), Act-HIB(R), Pentacel(R), Pediacel(R) and Pentaxim(R). We are also a leading producer of poliomyelitis (polio) vaccines, such as Ipol(R) and Imovax(R) Polio, as well as oral polio formulations, all of which contribute to polio eradication and disease control strategies in both developed and developing countries;
・Influenza vaccines such as Fluzone(R) and Vaxigrip(R), used for seasonal campaigns in both hemispheres. Additionally, we manufacture pre-pandemic avian influenza vaccines (including H5N1 vaccines) as part of the global pandemic preparedness efforts in both our French and U.S. facilities;
・Adult and adolescent booster vaccines protecting against pertussis, tetanus, diphtheria and polio. Our main products include: Adacel(R) (the first trivalent booster against pertussis, tetanus and diphtheria for adolescents and adults), Decavac(R), Repevax(R) and Revaxis(R);
・Meningitis vaccines, with Menomune(R), a bivalent Meningococcal A and C vaccine, and our main quadrivalent product Menactra(R) which was launched in the United States in 2005 and in Canada in 2006. Menactra(R) is a conjugate vaccine that is expected to provide a longer-lasting immune response;
・Travel, Endemic and Measles, Mumps and Rubella (MMR) vaccines, which include a wide range of products against hepatitis A, typhoid, rabies, yellow fever, Japanese encephalitis, cholera, MMR and anti-venoms. Key products include Imovax(R) Rabies, Verorab(R), Typhim Vi(R), Avaxim(R) and Vivaxim(R).
In 2006, our Vaccines activity was favorably impacted by the success of three products launched in 2005 in the United States (Decavac(R), Menactra(R) and Adacel(R)) and by a favorable influenza season.Our subsidiary sanofi pasteur is a fully integrated vaccine business offering the broadest range of vaccines in the industry. In 2006 sanofi pasteur immunized over 500 million people against 20 serious diseases and generated net sales of Eur2,533 million. Sales were very favorably impacted by the strong growth in markets outside of North America and Europe and the continued growth of Adacel(R) and Menactra(R), both launched recently in the United States. Sales growth was also due to strong global pediatric vaccine sales, the highly successful seasonal influenza vaccine campaigns and pre-pandemic influenza vaccine contracting activity with various governments.
Based on our estimates, sanofi pasteur is the world leader in the vaccine industry with a market share approximating 26% and holds a leading position in most countries. In the United States and Canada, which account for approximately 44% of the worldwide vaccines market, sanofi pasteur is the market leader with a market share approximating 35%.
In Europe, our vaccine products are marketed by Sanofi Pasteur MSD, a 50-50 joint venture between sanofi pasteur and Merck & Co, which serves 19 countries. With a 36% market share Sanofi Pasteur MSD is the market leader in Europe overall and in particular in France and the United Kingdom. In 2006, net sales of Sanofi Pasteur MSD, which are accounted for using the equity method, amounted to Eur724 million.
Sanofi pasteur has established a leading position in Latin America, has been expanding in Asia, particularly in China and India, and is very active in international publicly-funded markets such as UNICEF. We also have a significant activity in other developed, middle income and emerging markets throughout the world.
[2003] 人体用ワクチンはAventis Pasteur社に統合されている。 2003年, Aventis Pasteurは重篤な２０疾患で500億人分のワクチン1.4 billion doses を用意した。 ・2003年, Aventis Pasteurの売上は Euro 1,621 million(+2.5%; 2002年度Euro 1,580 million) ・1993～2002, Aventis Pasteurは、年間成長率15%(ワクチン業界全体12%)を維持。 ・世界ワクチン市場の50%を占める米国・カナダで、Aventis Pasteurはトップ２社の一つ。 売上の52%が北米。 西欧では, ワクチン事業はAventis Pasteur MSD(50-50合弁;Aventis PasteurとMerck & Co) が担当し１９カ国に販売。 同社は欧州で市場シェア37%で、特に仏・英・独が大きい。 欧州はAventis Pasteur売上の28%を占める。 Aventis Pasteur MSDの2003年売上は、Euro 591 million.●小児混合ワクチン 【2008】 【2007】 【2003】 ６種の疾患を想定している。(Diphtheria/Tetanus/Pertussis/Polio/Hib/Hepatitis B) 現在１０銘柄はDaptacel,ActHib以外のすべてにDTPの３種を含む。 ・Daptacel - 2002発売 diphtheria/tetanus ・Tripedia - pertussis, diphtheria and tetanus ・ActHib - Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate) ・Pentacel - DTP+Polio+Hibの５種。 1997発売、カナダでは予防標準。９カ国で認可 ・Pediacel - pertussis - diptheria - tetanus - poliomyelitis vaccine 2002年英国登録。 2004年中南米と東アジアで発売見込み●Influenza 【2009】
通年の売上高は4 億6,500 万ユーロ（H5N1 インフルエンザワクチンの売上高2,500 万ユーロを含む）となりました。季節性インフルエンザワクチンの売上高は、B 型株の生産収量が低かったことや新型インフルエンザA 型（H1N1）の大流行をうけて、第3 四半期から第4 四半期へ売上がシフトしたため、32.2%増の2 億200 万ユーロとなりました。全体として、2009 年度に、サノフィパスツールは、1 億回接種分の単価新型インフルエンザワクチンと1 億8,000 万回接種分の3 価季節性インフルエンザワクチンを含め、2 億8,000 万回接種分を超えるインフルエンザワクチンを供給しました。これは、北半球諸国の需要の40%、南半球諸国の需要の75%に相当すると推定されます。【2008】
通年におけるインフルエンザワクチンの純売上高は、1.5%増の7 億3,600 万ユーロとなりました。これには、第2 四半期に米国保健福祉省（HHS：Department of Health and Human Services）に出荷されたH5N1 ワクチンの1 億9,250 万ドル（前年同期は1 億1,300 万ドル）が含まれます。2008 年度の出荷の4 分の3 が第3 四半期に完了したため、第4 四半期における米国でのインフルエンザワクチンの売上高は、前年同期比で減少しました。【2007】
サノフィ･パスツールは、2007年度に1億8,000万服を超える季節性インフルエンザワクチンを生産し、世界リーダーとしての地位を固めました。出荷数は、世界市場の40%を占めると推定されます5。H5N1ワクチンの売上高を排除すると、季節性インフルエンザワクチンの売上高は2.6%増加しました。【2006】
・Influenza vaccines such as Fluzone(R) and Vaxigrip(R), used for seasonal campaigns in both hemispheres. Additionally, we manufacture pre-pandemic avian influenza vaccines (including H5N1 vaccines) as part of the global pandemic preparedness efforts in both our French and U.S. facilities;Sanofi pasteur is the world leader in the production and marketing of influenza vaccines. Sales of the influenza vaccines Fluzone(R) and Vaxigrip(R)/Mutagrip(R) have more than tripled since 1995 and annual production was increased to more than 170 million doses in 2006 to better meet an increasing demand. We expect the global demand for influenza vaccines to continue to grow strongly within the next decade, due to an increased disease awareness and wider government immunization recommendations. Given the heightened awareness of a potential influenza pandemic amongst health authorities, medical professionals and the public at large, the demand for influenza vaccines has increased in general. In 2005, we initiated a $160 million investment in the United States for a new influenza vaccine manufacturing facility, which will double our production capacity there and help to meet the increased demand from both inside and outside the United States. An additional Eur160 million investment has also been approved for a formulation and filling facility in Val de Reuil, France, to boost filling capabilities, mainly for influenza vaccines.
In April 2005, sanofi pasteur and the U.S. Health and Human Services Department (HHS) entered into a five-year agreement to speed the development of a production process for new cell culture influenza vaccines in the United States and to design a U.S.-based cell-culture vaccine manufacturing facility.
In recent years, influenza vaccine demand has experienced strong growth in many other countries --- including China, South Korea and Mexico. This trend is expected to continue over the coming years. Sanofi pasteur will remain focused on maintaining its leadership in the influenza market and in meeting the increased demand.Sanofi pasteur has contracted the following agreements to accelerate the development of influenza vaccines in anticipation of a possible pandemic:
・Agreement between sanofi pasteur and the U.S. government, signed in November 2006, for the production of a new type of pre-pandemic vaccine against the H5N1 strain of avian influenza, under which sanofi pasteur will receive $118 million for delivery of the vaccine. A similar contract worth $150 million was signed in 2005; deliveries under this contract were made during 2006. Sanofi pasteur has initiated similar projects in Europe and the rest of the world.
・Agreement between sanofi pasteur and the U.S. government, signed in April 2005, to speed the production process for new cell-culture pandemic influenza vaccines and design a production facility for cell-culture vaccines. The total amount payable to sanofi pasteur under the agreement is $97 million, of which $20 million was received in 2006.[2003] ・インフルエンザ市場規模Euro 1.2 billion; Aventisは38%のシェアと最大手 ・1998年以来、Fluzone and Vaxigrip/Mutagripは３倍増。●Polio 【2008】 【2007】 【2003】
・Aventisは不活化ポリオワクチンの世界最大メーカー。 米国名IPOL●Adacel(TM)（成人および青年用破傷風・ジフテリア・百日咳追加ワクチン）Adult and Adolescnt boosters 【2008】
米国で非常に優れた業績を収め、第4四半期に35.6%増の5,400 万ユーロ、通年に20.0%増の2 億5,500 万ユーロの純売上高を記録しました。【2007】
Adacel(TM)の純売上高は、64.5%増の2億3,400万ユーロとなりました。【2003】 ・Adacelを申請。 最初のtrivalent booster against diphtheria, tetanus and pertussis。 米国承認は2004年予定●Menactra(R) Meningitis 【2009】
Menactra®（髄膜炎菌性髄膜炎を予防する4 価結合体ワクチン）の純売上高は、1.1%増の4 億4,500 た。米国におけるMenactra Infant/Toddler の承認申請は、2010 年第2 四半期を予定しています。【2008】
通年におけるMenactra(R)（髄膜炎菌性髄膜炎の4 価ワクチン）の純売上高は、7.9%増の4 億400 万ユーロとなりました。【2007】
Menactra(R)の2007純売上高は、86.1%増の4億1,500万ユーロ
2007年10月に米国において、Menactra(R)の許可拡大が承認され、2～10歳の子供が適応範囲に含まれるようになりました。【2003】 ・Menomune - 当社は米国でmeningococcal meningitis用にa quadrivalent vaccineを提供する唯一のメーカー ・Menactra(a conjugate vaccine) - 長期持続の免疫反応を期待される。 2003.12 FDAにBLA申請。●Travelers/endemic area 【2008】 【2007】 【2003】 ・Aventis Pasteurは、種々の製品を提供 typhoid, rabies, yellow fever, Japanese encephalitis, and cholera.●Gardasil 子宮頸癌ワクチン 【2008】 【2007】
第4四半期に、ヨーロッパのメルク社とのジョイントベンチャーであるサノフィ･パスツールMSDは、Gardasil(R)（1億6,000万ユーロの純売上高）の成功に支えられ、決算ベース前年度比44.4%増の3億7,100万ユーロの売上高を記録しました。
サノフィ･パスツールMSDは、2006年末にヨーロッパでGardasil(R)の販売を開始しました。子宮頸がんの原因となる乳頭腫ウイルス感染に対する初のワクチンであるこの製品は、ジョイントベンチャーの対象範囲に含まれるヨーロッパの全19カ国で販売されています。 2007年度に、サノフィ･パスツールMSDは、決算ベース43.6%増の10億4,000万ユーロの売上高を記録しました。 通年におけるGardasil(R)の純売上高は、3億4,100万ユーロでした。サノフィ･パスツールMSDの売上高は、サノフィ･アベンティスのデータに連結されていません。【】 ●Pentacel(R)（ジフテリア、破傷風、百日咳、ポリオ、およびインフルエンザ菌b 型による感染症（ヒブ）を予防するアメリカで承認された初の小児用5 種混合ワクチン） 【2009】
Pentacel®（ジフテリア、破傷風、百日咳、ポリオ、およびインフルエンザ菌b 型（ヒブ）による感染症を予防する、2008年6月時点で米国初の小児用5種混合ワクチン）は、第4四半期に1億400万ユーロ（前年同期は5,700万ユーロ）、通年に3 億4,300 万ユーロ（同8,400 万ユーロ）の純売上高を計上しました。【2008】
2008 年7 月の発売以降、売上を伸ばし、第4 四半期に5,600 万ユーロ、通年に8,200 万ユーロの純売上高を計上して成功を収めました。【】 ●Act-Hib(R) 【2008】
米国での他社製品の供給不足の際、より多くのワクチンを提供するための製造、販売における努力と、日本での2008 年12 月のAct-Hib(R)発売によって、通年に19.9%増の1 億2,000 万ユーロの売上高を計上しました。
Act-HIB(R), for the prevention of Haemophilus influenzae type b infections, is also an important growth driver within the pediatric product line. In 2008, Act-HIB® became the first Hib vaccine to be approved in Japan. In the United States, sanofi pasteur successfully improved its market supply to respond to a competitor’s supply shortage.● 【2008】 【2007】 【】 ■全般 【2008】 【2007】
2007年4月にAmbien(R) （マイスリー）IRの保護が満了し、ヨーロッパでEloxatinRのジェネリック医薬品との競合【2006】
2006年度年初から9か月間における米国でのAllegraR（アレグラ）、AmarylR（アマリール）、AravaR（アラバ）、DDAVPRのジェネリック医薬品の影響が製品構成の改善により完全に相殺されなかったため、0.3ポイント悪化して26.6%となりました。
1億7,600万ユーロの再編成費用は、グループが市場環境の変化に順応する取り組みに関連したものです。有形固定 資産および無形固定資産の減損費2億1,700万ユーロは、主にKetek（ケテック）[telithromycin]に関わる産業資産の減損に関連しています。
その他の営業収益および費用は、5億3,600万ユーロとなりました。このデータには、Rに関する4億6,000万ユーロ（税引後3億8,400万ユーロ）、および動物用栄養食品事業の残り30%の株式売却に関する4,500万ユーロを含む5億5,000万ユーロの売却益が含まれます。2006年1月12日、Pfizer社は、吸入型インスリン・Exuberaの全世界での独占権利をsanofi-aventis社から130億ドルで買い取る * Arixtra & Fraxiparineの販売権をGSKにむ売却[2004.9.1]。 * Campto の販売権は、Pfizerに売却。■血栓・循環器 ●Plavix (clopidogrel) 【2009】
通年におけるPlavix®（プラビックス）の世界的プレゼンスは、が58.9%増（3 億3,900 万ユーロ）と堅調に成長したことにユーロを突破しました（14.4%増の11 億5,200 万ユーロ）。【2008】
通年における米国でのPlavix(R)（プラビックス）の売上高（ブリストル・マイヤーズ スクイブ社（BMS）に連結）は、年度前半にジェネリック医薬品との競合の影響を受けた前年度と比べて急増しました。ヨーロッパでは、ドイツで8 月以降に、単剤療法セグメントで複数のベジル酸クロピドグレルとの競合による影響を受け、Plavix(R)（プラビックス）/Iscover(R)の市場シェアが数量ベースで12 月（IMS Pharmatrend 調べ、2008 年12 月22 日週）の75%程度に留まったことを反映し、伸長率は3.2%となりました。「その他」の国では、日本で第4 四半期に6,700 万ユーロ（前年同期は3,300 万ユーロ）、通年に1 億8,200 万ユーロ（同6,600 万ユーロ）の純売上高を達成して成功を収めたことにより、Plavix(R)（プラビックス）が伸長しました。Plavix(R) (clopidogrel bisulfate), a platelet adenosine diphosphate (ADP) receptor antagonist with a rapid onset of action that selectively inhibits platelet aggregation induced by ADP, is indicated for long-term prevention of atherothrombotic events in patients with a history of recent myocardial infarction, recent ischemic stroke or established peripheral arterial disease. Plavix(R) is currently the only drug indicated for the secondary prevention of atherothrombosis regardless of the location of the arteries initially affected (heart, brain, lower limbs). This indication is supported by the results of the landmark CAPRIE trial, including almost 20,000 patients. CAPRIE demonstrated the superior efficacy of Plavix(R) over acetylsalicylic acid (ASA, the active ingredient of Aspirin(R)), with a comparable safety profile.
Following the significant results of the CURE, CLARITY and COMMIT clinical trials, Plavix(R) is now also indicated for the treatment of acute coronary syndrome with and without ST segment elevation (ACS; Q-wave and non-Q-wave myocardial infarction and unstable angina) in combination with ASA. These indications are incorporated into the guidelines of the American Heart Association, the American College of Cardiology and the European Society of Cardiology.
In addition to the 75mg tablet, a new Plavix(R) 300mg tablet was launched in over 15 countries during 2008.
This new 300mg tablet reinforces Plavix(R) early use by simplifying its approved loading dose administration in patients with acute coronary syndrome (unstable angina, myocardial infraction). The 300mg tablet is bioequivalent to four 75 mg tablets of Plavix(R).The extensive clinical program for Plavix(R) including all completed, ongoing and planned studies, is one of the largest of its kind and has involved more than 100,000 patients overall. In addition, over 92 million patients worldwide are estimated to have been treated with Plavix(R) since its launch, providing significant evidence of real-life efficacy and safety experience with this product.
The ongoing clinical trials that are designed to support the long-term value of Plavix(R) by providing complementary clinical data include:
kﾎ The ACTIVE study, which is intended to assess the value of Plavix(R) on top of ASA compared with ASA alone in patients with atrial fibrillation (who cannot take an oral anticoagulant) for the reduction of cardio-embolic and atherothrombotic events. This study has completed recruitment (14,000 patients included, currently in the follow-up phase). While one arm of the study kﾀ ACTIVE-W kﾀ was terminated early, the other two arms, ACTIVE-A and ACTIVE-I, are ongoing. The results of both ACTIVE-A and ACTIVE-I are expected in 2009;
kﾎ The CURRENT study, which aims to optimize the dosing regimen of clopidogrel bisulfate in 25,000 patients with ACS scheduled for percutaneous coronary intervention. A loading dose of 600 mg followed by 150 mg daily for 6 days then followed by 75 mg daily up to the end of the study (30 days) is compared to the currently approved regimen (300 mg loading dose followed by 75 mg daily). The recruitment started in 2006 and results are expected in 2009; and
kﾎ Following an FDA written request for pediatric data, the development of a pediatric indication for Plavix(R) in the United States is ongoing. The dose ranging Phase II (PICOLO study) has helped determine the right dose to be studied in Phase III (CLARINET). CLARINET is ongoing and results are expected in 2010. A pediatric investigational plan was approved in 2008 by the European Medicines Agency.Plavix(R) is marketed in over 115 countries, including the United States, through our alliance with Bristol-Myers Squibb (BMS).
Sales of Plavix(R) in Japan are consolidated by sanofi-aventis and are outside the scope of our alliance with BMS. In Japan, a New Drug Application (NDA) for marketing authorization was approved in January 2006 for the reduction of recurrence after ischemic cerebrovascular disorder and launch took place in May 2006. In October 2007, the Japanese Health Authorities approved a new indication in cardiology for patients with Acute Coronary Syndrome for whom percutaneous coronary intervention is being planned.
Plavix(R) is the leading antiplatelet in the European and the U.S. markets (source: IMS 2008 sales, all available channels). Germany has been affected by competition from clopidogrel besylates since August 2008 in the monotherapy segment. The share of the German market by volume retained by Plavix(R)/Iscover(R) in December 2008 remains approximately 75% (source: IMS Pharmatrend, week of December 22, 2008).
【2007】
2007年6月19日、米国ニューヨーク州南部地方裁判所は、Plavix(R)（プラビックス）の有効成分である硫酸クロピドグレルを保護する米国特許の有効性と強制力を支持し、アポテックス社が硫酸クロピドグレルのジェネリックを特許保護が満了するまでに米国で販売することを禁止する恒久的な差し止め命令を下しました。アポテックス社は2006年8月、硫酸クロピドグレルのジェネリックを発売しました。その後2006年8月31日、米国ニューヨーク州南部地方裁判所はアポテックス社に対し、それ以降の硫酸クロピドグレルのジェネリックの販売中止を命令する仮差し止め命令を下しましたが、すでに出荷された製品の回収までは命令しませんでした。この製品の主要特許は、米国において2011年11月まで保護されます。
第4四半期における米国でのPlavix(R)（プラビックス）の売上高（BMSに連結）は、ジェネリック版の提供による影響を受けていた前年同期の3億4,800万ドルに対し、11億8,000万ドルに達しました。通年におけるPlavix(R)（プラビックス）の売上高は、前年同期の26億7,200万ドルに対し、40億7,200万ドルとなりました。
第4四半期におけるヨーロッパでのPlavix(R)（プラビックス）の純売上高は、依然としてドイツでの並行輸入の影響を受け、5.0%増の4億5,800万ユーロに留まりました。
「その他」の国では、第4四半期に売上高伸長率が加速し、27.8%増の2億2,500万ユーロとなりました。これは、5月に日本で、2週間の処方制限を解除され、売上高伸長率が高まったことが要因です。第4四半期における日本での売上高は、前年同期の400万ユーロに対し、2,700万ユーロとなりました。通年では、日本におけるPlavix(R)（プラビックス）の売上高は、前年同期の1,100万ドルに対し、6,100万ドルとなりました。【2006】
2006年8月8日、アポテックス社は、Plavix(R)（プラビックス）と競合する硫酸クロピドグレル75 mg錠の ジェネリック版を米国で発売したことを発表しました。2006年8月31日、米国ニューヨーク州南部地方裁判所は、サノフィ･アベンティスとブリストル・マイヤーズ スクイブ社が申し立てた仮命令申請を認め、アポテックス社に対し、硫酸クロピドグレルのジェネリック版の販売停止を命じました。ただし、裁判所は、アポテックス社がすでに販売した製品の回収は命じませんでした。 その結果、2006年8月8日以降の米国での売上高が大きな打撃を受けました。第4四半期における米国でのPlavix(R)（プラビックス）の売上高は、2億7,300万ユーロとなりました。硫酸クロピドグレルの処方数（TRx）の伸長率は、第4四半期は11.8.%6、2006年度通年では13.0%7と、堅調に推移していました。12月最終週に、硫酸クロピドグレルの処方数に占めるPlavix(R)（プラビックス）の割合が急拡大し、44.3%8に達しました（9月最終週の時点では21.3%8）。
2006年8月、米国食品医薬品局は、ST上昇急性心筋梗塞患者のあらゆる原因による死亡率、および梗塞再発・脳卒 中・死亡の複合エンドポイントの発生率を低減するPlavix(R)（プラビックス）の新たな適応を承認しました。EUでも、同じ適応が2006年9月に承認されました。
日本では、虚血性脳血管障害（心原性脳塞栓症を除く）後の再発抑制として、Plavix(R)（プラビックス）が発売されています。6カ月間の市販後直後調査が第4四半期に終了しましたが、同じく当局から課せられた2週間という処方制限は、2007年5月まで継続します。通年の純売上高は1,200万ユーロでした。2006年末には、急性冠症候群の治療薬としてのPlavix(R)（プラビックス）の承認申請が行われました。●Lovenox/Clexane (enoxaparin sodium) 【2009】
市場で上位を占める低分子ヘパリン（LMWH）、Lovenox®（クレキサン）の第4 四半期における純売上高は、米国の好業績（9.2%増の4 億4,300 万ユーロ）に牽引され、8.1%増の7 億5,400 万ユーロとなりました。通年の純売上高は、ヨーロッパ（13.7%増の8 億9,000 万ユーロ）と「その他」の国（14.8%増の3 億3,100 万ユーロ）の好業績に牽引され、8.8% 増加しました。【2008】
市場で上位を占める低分子ヘパリン（LMWH）、Lovenox(R)（クレキサン）の第4 四半期における純売上高は、8.4%増の7億4,900 万ユーロとなりました。米国では、7.2%の伸長を記録しました。ヨーロッパでは、（少量の不純物が含まれていた一部のバッチを回収したために）2 四半期にわたって製品の入手が限られたことの影響を受けていましたが、第4 四半期 には、2 桁成長となる11.1%増の2 億2,100 万ユーロの純売上高を達成しました。2008 年度通年における同製品の純 売上高は、10.6%増の27 億3,800 万ユーロとなりました。Lovenox(R) (enoxaparin sodium) is the most widely studied and used low molecular weight heparin (LMWH)in the world. It has been used to treat an estimated 200 million patients in 100 countries since its launch and isapproved for more clinical indications than any other LMWH. A comprehensive dossier of clinical studies hasdemonstrated the benefits and safety of Lovenox(R) in the prophylaxis and treatment of deep vein thrombosis(DVT) and in acute coronary syndromes (ACS). It has become the product of reference in clinical trials for thedevelopment of new anticoagulants in both venous and arterial indications.
In the field of venous thromboembolism (VTE) prevention, Lovenox(R) use continues to grow especially forprevention of VTE in medical patients.
The initial findings of the EXCLAIM trial had demonstrated the benefit of extended thromboprophylaxis inacutely ill medical patients with reduced mobility. Further analyses presented at the American Society ofHematology Congress in December 2008 have demonstrated that some patient populations, such as the elderly(aged 75 and above) or stroke patients, may potentially benefit more than the overall population from extendedtreatment.
Lovenox(R)/Clexane(R) was approved for marketing in Japan for the prevention of VTE in patients undergoingorthopedic surgery of the lower limbs such as total hip replacement, total knee replacement and hip fracturesurgery in January 2008 and in patients undergoing abdominal surgery in February 2009.
In the cardiovascular area, Lovenox(R) was approved in the United States in 2007 for the treatment of patientswith ST-segment Elevation Myocardial Infarction (STEMI) based on the results of the ExTRACT-TIMI 25 trial,and since then has been approved in more than 40 countries worldwide for this indication.
Supporting the results of the ExTRACT PCI sub-study showing that Lovenox(R) can be safely used beforeand in the catheterization laboratory data from the STACKENOX trial were presented at the European Society ofCardiology meeting in September 2008. STACKENOX showed that using standard dosing of Lovenox(R) issufficient to provide proper anticoagulation levels. It also provided new evidence against the practice ofadministering unfractionated heparin to patients who already received enoxaparin sodium, as it results in overanticoagulation that may lead to excess bleeding as seen in trials like OASIS 5.
In terms of medical practice registries, GRACE (the Global Registry of Acute Coronary Events) hasevaluated over 100,000 patients worldwide with acute coronary syndrome as of today and has led to thepublication of more than 75 manuscripts in a variety of peer review medical journals. Furthermore, the GRACERisk Score has been incorporated into various international guidelines on the treatment of patients with ACS,providing a valuable tool to physicians treating those patients.
Lovenox(R)/Clexane(R) is the leader in antithrombotics in the United States, Germany, France, Italy, Spain, andthe United Kingdom (source: IMS 2008 sales, all available channels).
【2007】
市場で上位を占める低分子量ヘパリン（LMWH）製剤、Lovenox(R)の純売上高は、17.4%増の6億7,400万ユーロとなりました。この製品は、3つの地域すべてにおいて堅調な成長を記録しました（米国16.5%、ヨーロッパ15.5%、「その他」の国27.9%）。米国では、引き続き、内科的な予防における利用増が主な成長要因となっています。
2008年1月に、Lovenox(R)は、「股関節全置換術、膝関節全置換術、股関節骨折手術など、下肢整形外科手術施行患者における静脈血栓塞栓症（VTE）発症抑制」の効能･効果として、日本で承認されました。日本において、静脈血栓塞栓症のリスクがある腹部手術を受ける患者への同製品の適応拡大を目指し、さらなる治験が行われています。【2006】
市場で上位を占める低分子量ヘパリン（LMWH）のLovenox(R)の第4四半期における純売上高は、11.8%増の6億1,400万ユーロとなりました。同製品の伸長は、内科的な予防において同製品の利用が増加したことによるものです。ヨーロッパでの売上高は、12.9%増加しました。
ST上昇急性心筋梗塞患者の治療薬（ExTRACTスタディ）としてのLovenox(R)の承認申請は、ヨーロッパおよび米国ともに第4四半期に行われました（FDAから優先審査に指定されました）。この新たな適応により、未分画ヘパリンに対するLovenoxの優位性がさらに高まることが期待されます。
2006年12月に米オーランドで開催された米国血液学会議（ASH：American Society of Hematology）の第48回年次会 議で、PREVAILスタディの最終結果が発表されました。この結果により、急性虚血性脳卒中で入院した患者においてエノキサパリンを使用すると、未分画ヘパリン（UFH）と比較して静脈血栓塞栓症（VTE）イベントが有意に43%減少することが証明されました。[2003] ・世界で最も研究を重ね、広範に使用されているlow-molecular-weight heparin (LMWH) 1987年発売以来96カ国1.18億人が使用。 ・有効性と安全性。 deep vein thrombosisの発生が少ない。 アスピリンとの併用で、ischemic complications of unstable angina (UA) and non- Q-wave myocardial infarction (NQWMI)の予防に有効 ・300 mg/3 mL multiple-dose vial - 2003.3 米国発売。 prefilled syringes equipped with an Automatic Safety Device and a sharper needle が2003年後半に発売。 ・Lovenox - 人工心臓弁装着(妊婦含む)患者についての添付文書改訂し、それに伴う追加 申請(sNDA)をFDAは2003.中間に認可。 ・ジェネリック問題 - 2003.2 AventisはFDAに市民請願書を提出。 1)Lovenoxの文献を引用したANDAを認めないこと 2)ジェネリック製品がcontains a 1,6 anhydro ring structure at the reducing ends of between 15% and 25% of its polysaccharide chains. Lovenox is a market leader in all major countries, including - 米国(rank: #1,シェア86.3%), France (rank: #1,シェア58.3%, Germany (rank: #1,シェア27.8%), Italy, Spain and the UK. [2002] ・2002.11 FDAが追加適応を承認。 for the prevention of life-threatening blood clots in medical patients with severely restricted mobility during acute illness.●Aprovel (irbesartan) 【2008】
厳しい競争環境にもかかわらず、2008 年度通年におけるAprovel(R)の世界売上高は、2 桁成長を達成しました。2008 年9 月、EMEA の医薬品委員会（CHMP：Committee for Medicinal Products for Human Use）は、ヨーロッパで単剤療法としてイルベサルタンのジェネリック医薬品を承認する件に関し、肯定的見解を示しました。しかしながら、イルベサルタンの有効成分は、主なヨーロッパ諸国において2012 年8 月まで特許が保護されます。一部の国（スペイン、ポルトガル、フィンランド、ノルウェー、および東欧の一部）では、イルベサルタンは、この成分特許によって保護されていません。ただし、各国に応じて、その他の特許が有効になる可能性があります。成分特許が適用されないヨーロッパ諸国において、単剤療法としてのAprovel(R)が2008 年に記録した純売上高は5,000 万ユーロでした。
Aprovel(R) (irbesartan) belongs to the fastest growing class of antihypertensives, angiotensin II receptor antagonists. These highly effective antagonists act by blocking the effect of angiotensin, the hormone responsible for blood vessel contraction, thereby enabling blood pressure to return to normal. In addition to Aprovel(R)/Avapro(R)/Karvea(R), we also market CoAprovel(R)/Avalide(R)/Karvezide(R), a fixed dose combination of irbesartan and hydrochlorothiazide (HCTZ), a diuretic that increases the excretion of water by the kidneys and provides an additive blood pressure lowering effect. These products achieve control of blood pressure in over 80% of patients with a very good safety profile.
Aprovel(R) and CoAprovel(R) tablets are available in various dosages, to fit the needs of patients with different levels of hypertension severity.
Aprovel(R) is indicated as a first-line treatment for hypertension and for the treatment of nephropathy in hypertensive patients with type 2 diabetes, in both Europe and the United States. CoAprovel(R) may be used in appropriate patients whose blood pressure is not adequately controlled on monotherapy, and as initial therapy in appropriate patients who are likely to need multiple drugs to achieve their blood pressure goals (in the United States only).
Several clinical trials have been undertaken in recent years in an effort to demonstrate the effects of Aprovel(R) beyond blood pressure control:
kﾎ The i-PRESERVE study evaluated the effect of irbesartan in the treatment of heart failure with preserved ejection fraction (also called diastolic heart failure), a very specific disease for which there is no reference treatment. The results were published in November 2008 and were consistent with previous trials conducted in this patient population. Although the study did not meet its principal end point in terms of efficacy, i-PRESERVE confirmed the good safety profile of irbesartan in an already welltreated population.
kﾎ ACTIVE-I evaluates the efficacy of Aprovel(R) combined with clopidogrel bisulfate (the active ingredient in Plavix(R)), in preventing complications in patients suffering from atrial fibrillation. We began this clinical program in 2003, with enrolment for the 10,000-patient study ongoing. Results are expected by late 2009.Aprovel(R) and CoAprovel(R) are marketed in more than 80 countries, including the United States kﾀ under the brand names Avapro(R) and Avalide(R), respectively kﾀ through an alliance with Bristol-Myers Squibb (BMS).
In Japan, where the product is licensed/sub-licensed to Shionogi Co., Ltd and Dainippon Sumitomo Pharma Co., Ltd, respectively, specific 50 mg and 100 mg dosages developed for the Japanese market were launched in June 2008.
In 2008, based on the total sales of Aprovel(R)/Avapro(R)/Karvea(R) and CoAprovel(R)/Avalide(R)/Karvezide(R), our main markets are Europe and the United States, where we rank second and fourth respectively among the angiotensin II receptor antagonists in the hypertension market (source: IMS, 2008 sales).
【2007】 【】 ●Multaq(R) (dronedarone, SR33589) 抗不整脈剤/atrial fibrillation 【2009】
心房細動・心房粗動患者さんにおける心血管系理由による入院を減少させるという臨床ベネフィットを持つ初の承認薬であるMultaq®は、米国では、説得力のある医薬品の経済性評価データと臨床エビデンスに基づき、マネジドケアの払い戻しに関して、大きな進展を達成しました。現時点で、加入者の60%近くについて、有利なTier 2 フォーミュラリーの位置づけを確保しつつ、保険償還対象となっています。2009 年度の処方件数は累計9 万400 件以上（IMS NPA）を記録し、処方傾向は予測どおりです。2009年11月30日、欧州委員会からMultaq®の販売承認を取得しました。2010年1月、EU で最初にMultaq®を発売した国はドイツでした。Multaq®は、カナダとスイスでも販売されており、ブラジルとメキシコで承認されています。2009年11月、サノフィ･アベンティスは、心房細動患者さんの心血管リスクプロファイルに関する理解向上と心血管系アウトカムの特徴づけを目的とした大規模な新しい症例登録調査「RealiseAF」を開始しました。この症例登録調査では、世界中の心房細動患者さん1 万人以上の参加を目指しています。【2008】
The results of the ATHENA trial showed a statistically significant 24% reduction of cardiovascular hospitalization or death in patients with atrial fibrillation (AF). In addition, a decreased risk of stroke by 34% in patients with AF already adequately treated by antithrombotic therapy was demonstrated. In ATHENA, dronedarone significantly reduced the total number of hospital nights by 28% and decreased by 35% the total length of time spent in hospital for cardiovascular reasons. DIONYSOS study results showed the respective profiles of dronedarone and amiodarone: in the primary endpoint, atrial fibrillation after electrical cardioversion occurred in 36.5% of patients in the dronedarone arm versus 24.3% of patients in the amiodarone arm. However, in the dronedarone arm less thyroid events (2 versus 15), neurological events (3 versus 17) and premature study drug discontinuation due to any adverse events (13 versus 28) were observed. The FDA granted a priority review status for the use of Multaq(R) in patients with AF in August 2008. In November 2008, the FDA informed sanofi-aventis that they intended to discuss the Multaq(R) (dronedarone) application at the Cardio- Renal Advisory Committee on March 18, 2009.●Celivarone (SSR149744) 抗不整脈剤/Phase IIb 【2008】
Following the results of the ICARIOS trial, which demonstrated celivarone’s effects on reducing the firing rate of implantable cardioverter/ defibrillator (ICD) by 46% for either ventricular tachycardia or fibrillation versus placebo, the development of celivarone was stopped in atrial fibrillation. Its future development will depend on the outcome of the Multaq(R) Advisory Committee on March 18, 2009.日本では「心房細動」の適応でP2/3●XRP0038 (NV1FGF)/non-viral fibroblast growth factor 1, 重症虚血肢(critical limb ischemia); Phase III 【2008】
XRP0038 is an injectable non-viral DNA plasmid and gene therapy-based approach for the promotion of angiogenesis in patients with peripheral arterial disease that statistically significantly prolonged time to amputation as compared to placebo in a Phase IIb study in patients with critical limb ischemia. A Phase III program (TAMARIS study) is currently ongoing. The primary objective is to demonstrate the safety and effectiveness of XRP0038 in the prevention of major amputations in critical limb ischemia patients. Submission is planned for end of 2010.日本では「重症下肢虚血を伴う末梢動脈閉塞性疾患」の適応でP3●Delix/Tritace (ramipril) 【2008】
Tritace(R) (ramipril) is an angiotensin converting enzyme (ACE) inhibitor indicated for the treatment of hypertension, congestive heart failure following or in the absence of acute myocardial infarction and nephropathy.The Heart Outcomes Prevention Evaluation (HOPE) study showed it to be effective in reducing the incidence of stroke, heart attacks and cardiovascular-related death in high-risk patients. Tritace(R) is the only ACE inhibitor approved for the prevention of stroke, heart attack and death in these patients and has the broadest spectrum of indications among ACE inhibitors for the treatment of cardiovascular disease.
The most recent European Society of Hypertension (ESH) / European Society of Cardiology (ESC) guidelines on the management of hypertension have highlighted the importance of taking global cardiovascular risk into account and the need to control hypertension. Based on the protective effect confirmed in the ON-TARGET study, the available combinations with diuretics (ramipril + hydrochlorothiazide) and calcium channel blockers (ramipril + felodipine) are listed as preferred combinations in the recent guidelines for physicians to help patients reach their blood pressure goals without worsening their metabolic profile.
Tritace(R) (ramipril) is available in tablets and capsules. It is marketed in over 70 countries. We have no rights on this product in the United States. Launches in several countries in Eastern Europe, the Middle-East and Asia are scheduled in 2009.
The three leading countries for sales of Tritace(R) in 2008 were Italy, Poland and Canada (source: IMS, 2008 sales). Generic ramipril became available in Italy in 2008, negatively affecting our sales there.
【2007】
第4四半期におけるTritace(R)の純売上高は、カナダでのジェネリック医薬品の発売による悪影響を受け、28.3%減の1億9,500万ユーロとなりました。【2003】 Canada (rank: #1,シェア27%), France (rank: #1,シェア10.7%), the UK (rank: #1,シ ェア24%), Germany, Spain and Italy. The U.S. rights were sold in 1998. ・ACE阻害剤で、高血圧、心筋梗塞後の鬱血性心不全、nephropathyに用いる。 ・HOPE study(2000)の第一次発表で、ハイリスク患者で脳卒中や心臓発作の発生、循環系 による死亡が低減されることが明らかとなってから、使用が増加。 ・Delix/Tritaceは、ハイリスク患者で脳卒中や心臓発作の発生、循環系による死亡の低 減の予防を認可された唯一のACE阻害剤。 ・Circulationで発表された最新報告で, Delix/Tritaceは消耗(debilitating)率を顕著に低減 、致命的心不全を強力に低下させる。 これは、Heart Outcomes Prevention Evaluation (HOPE)のsub-analysis。 ・HOPE-TOO (HOPE － The Ongoing Outcomes) studyの発表(2003.9) Delix/Tritace は２型糖尿病、心不全のリスク下で心臓疾患の予防効果を示した。 [2002] ・2002.4 Delix/Tritaceはドイツで承認。 ハイリスク患者で脳卒中や心臓発作の発生、 循環系による死亡の低減の予防。 この適応で欧州数カ国で認可済み■癌 ●Taxotere (docetaxel) タキソテール注(ドセタキセル水和物) 【2009】
Taxotere®（タキソテール）は、第4 四半期に4.1%増の5 億3,300 万ユーロの純売上高を記録しました。通年の純売上高は、6.1%増の21 億7,700 万ユーロとなりました。10 月、サノフィ･アベンティスは、リンパ節転移を伴わない早期乳がんのアジュバント療法としてのTaxotere®（タキソテール）に関し、ヨーロッパで販売承認の申請を行いました。11 月、欧州医薬品審査庁（EMA：European Medicines Agency）は、ヨーロッパでTaxotere®（タキソテール）のバイアル製剤を承認しました。この新しい製剤については、米国でも2008 年12 月に承認申請を行っています。2009 年11 月、FDA からの書面による依頼に応え、Taxotere®（タキソテール）に関する小児データを米国での承認申請のために提出しました。【2008】
Taxotere(R)（タキソテール）は、第4 四半期にも優れた業績を収め、特に米国では、乳がんのアジュバント療法と前立腺がんでの使用に後押しされ、純売上高が16.9%増の2 億800 万ユーロとなりました。通年の売上高は、2008 年に初めて20億ユーロを突破し（20 億3,300 万ユーロ）、3 つの地域すべてにおいて2 桁成長を記録しました（米国15.9%、ヨーロッパ 10.8%、「その他」の国13.8%）。Taxotere(R) (docetaxel), a taxoid class derivative, inhibits cancer cell division by essentially “freezing” the cell’s internal skeleton, which is comprised of microtubules. Microtubules assemble and disassemble during a cell cycle. Taxotere(R) promotes their assembly and blocks their disassembly, thereby preventing many cancer cells from dividing and resulting in death in some cancer cells.
Taxotere(R) is available in more than 100 countries as an injectable solution. It has gained approval for use in eleven indications in five different tumor types kﾀ breast, prostate, gastric, lung and head and neck. Taxotere(R) is indicated for early stage and metastatic breast cancer, first-line and second-line metastatic non-small cell lung cancer (NSCLC), androgen-independent (hormone-refractory) metastatic prostate cancer, advanced gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction and for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck.
In breast cancer, Taxotere(R) in combination with carboplatin and Herceptin(R) (TCH) was approved by the FDA in early stage breast cancer in May 2008. This combination, which presents a better safety profile than the anthracycline-based treatment, allows the treatment of a larger number of patients with Taxotere(R). The TCH treatment combination is now a standard of care in United States for patients with early stage breast cancer, HER2 positive and node positive. In Europe too, Taxotere(R)-based treatments excluding anthracycline are prescribed to an increasing number of patients with early stage localized breast cancer.
Taxotere(R) was approved in September 2008 by the Japanese Ministry of Health, Labor and Welfare (MHLW) following a supplemental New Drug Application (sNDA) for a new indication as a treatment of metastatic hormone refractory prostate cancer. Only a limited number of drugs with health insurance coverage are used to treat mHRPC in Japan. For this reason, Japanese urologists quickly recognized Taxotere(R) as the standard of care in this indication. In the United States and Europe, Taxotere(R) is also considered as the standard treatment in this indication.
Important new results of clinical studies on Taxotere(R) presented in 2008, in major international oncology conferences, should lead to a more frequent use of Taxotere(R) for patients with breast, prostate or head and neck cancers:
kﾎ The GEICAM 9805 trial, including 1,100 patients with node negative early stage breast cancer, demonstrated a significant survival benefit in favor of the Taxotere(R) regimen compared to a fluorouracil-based regimen. Efficacy results were presented during the 44th annual meeting of the American Society of Clinical Oncology (ASCO). Those new data will be part of the EMEA and FDA dossier planned to be filed in the first quarter of 2009 for a new indication of Taxotere(R) in association with doxorubicin and cyclophosphamide for the treatment of patients with node negative early stage breast cancer.
kﾎ For patients with androgen-independent (hormone-refractory) metastatic prostate cancer, the results of the Triade retrospective study presented at ASCO demonstrated that re-treatment with Taxotere(R) after a first-line treatment with Taxotere(R) is feasible and efficient.
kﾎ The first clinical trial comparing the Taxotere(R)-based induction treatment with a treatment without induction for patients with locally advanced head and neck cancer was presented at the 44th ASCO meeting. An induction treatment is aimed at reducing the tumor size before a chemo-radiotherapy. The results demonstrated significant efficacy results on the primary endpoint in favor of the Taxotere(R)-based induction compared to chemo-radiotherapy alone. This could make the induction-based treatment the new standard of care in this indication. The results of the clinical trial have been submitted to the Journal of Clinical Oncology with an expected publication date in the first half of 2009.The top four countries contributing to the sales of Taxotere(R) in 2008 were the United States, France, Germany and Japan (source: IMS, 2008 sales).
【2007】
第4四半期にTaxotere(R)（タキソテール）は、ヨーロッパで16.8%、「その他」の国で22.5%と堅調な伸長を記録しました。米国では、前四半期の成長率に沿って、同製品の純売上高が8.3%伸長しました。
12月に、サノフィ･アベンティスはBCIRG-006スタディに基づき、Taxotere(R)（タキソテール）を乳がんのアジュバント療法としてHerceptin(R)との併用に含めるよう、欧州医薬品審査庁（EMEA：European Medicines Evaluation Agency）に申請しました。
12月に、第30回サンアントニオ乳がんシンポジウム（SABCS：San Antonio Breast Cancer Symposium）で発表され た結果により、手術後の早期乳がん患者では、Taxotere(R)（タキソテール）とシクロフォスファミドを併用する試験的化学療法レジメンにより、アントラサイクリン系薬剤ベースの標準化学療法レジメンと比較して生存期間が有意に改善することがわかりました。この結果は、7年間の追跡期間中央値に基づいています。【2006】
第4四半期にTaxotere(R)（タキソテール）は、「その他」諸国で11.8%、ヨーロッパで9.9%と堅調な伸長を記録しました。
米国では、引き続き厳しい競争環境の中で、同製品は1.2%増の1億7,400万ユーロの売上高を記録しました。
2006年12月14日、BCIRG 006第III相試験（乳がん）から得られた有効性と安全性に関する第2回中間解析結果が、第29回サンアントニオ乳癌シンポジウム（San Antonio Breast Cancer Symposium）で発表されました。これらの結果から、追跡期間中央値3年目に、Herceptin(R)とTaxotere(R)（タキソテール）の併用療法により、早期のHER2陽性乳がん患者の無病生存率が有意に改善されることが確認されました。2006年に、Taxotere(R)（タキソテール）について、米国およびヨーロッパで以下の2件の新たな適応が承認されました。 - 進行胃がんにおける標準的治療（シスプラチンと5-FU）との併用 - 頭頸部がん患者に対する導入療法として従来療法（シスプラチンと5-FU）との併用 [2003] - 米国(rank: #1,シェア30.2%), France (rank: #2,シェア24.9%) and Japan (rank: #3,シェア12.8%) ・主に転移性(metastatic)乳癌と非小細胞肺癌(NSCLC)に用いる。 ・1995年に発売以来も86か国で販売。 ・早期乳癌、前立腺癌、頭頚部癌、胃癌に適応拡大で臨床試験中 ・切除不可の進行性・転移性非小細胞肺癌(NSCLC)のCDDP併用によるfirst-line therapy ～2003.1 EU承認。 FDA承認2002.11、日本でも承認済み ・2003.6 ASCOでTAX 325(進行性胃癌の国際的大規模Phase III研究)の中間報告。 ～標準化学療法より延命率が高い。paclitaxelとの比較で [2000] ・2000 EUで追加適応承認。 1)非小細胞肺癌(NSCLC)のsecond-line treatment 2)進行性・転移性乳癌患者ヘドキソルビシン併用●Eloxatin 【2009】
第4 四半期のEloxatin®の純売上高は80.5%減の6,700 万ユーロであり、医薬品事業の売上高合計に占める割合はわずか1.1%となりました。この業績は、2009 年8 月に米国でジェネリック医薬品が発売されたことを反映したものです。第4四半期における米国での純売上高は、97.4%減の700 万ユーロとなりました。通年の純売上高は、34.7%減の9 億5,700 万ユーロとなりました。【2008】
Eloxatin(R)は、転移性結腸直腸がんのアジュバント療法および第一選択薬におけるトップクラスの細胞障害性薬剤であり、アジュバントでの使用に後押しされ、米国において、第4 四半期に6.9%増の2 億6,500 万ユーロ、通年に6.2%増の9 億4,800 万ユーロの純売上高を記録しました。「その他」の国では、13.4%増の1 億8,600 万ユーロと堅調な伸長を記録 しました。Eloxatine(R) (oxaliplatin) is a platinum-based cytotoxic agent.
Eloxatine(R) is indicated in combination with 5-fluorouracil and folinic acid in adjuvant treatment of stage III colon cancer patients who have undergone complete resection of the primary tumor and for the treatment of advanced carcinoma of the colon or rectum (metastatic colorectal cancer).
The development of Eloxatine(R) has led to major progress in the treatment of metastatic colorectal cancer.
Thanks to its demonstrated ability to reduce the size and number of liver metastases, Eloxatine(R) increases the chances of having complete surgical removal of liver metastases and has given the hope of a potential cure in a significant proportion of patients with initially unresectable liver metastases. Furthermore, in patients with resectable liver only metastases from colorectal cancer, the results of the EPOC study demonstrated that perioperative chemotherapy with Eloxatine(R) given in combination with 5-fluorouracil/folinic acid leucovorin (the FOLFOX regimen) significantly reduced the risk of relapse compared to surgery alone.Due to its consistently high and sustained efficacy in treating metastatic colorectal cancer, the FOLFOX regimen is a mainstay treatment of metastatic colorectal cancer in the United States, Europe and certain countries in the Asia-Pacific region.
Eloxatine(R) has been developed for adjuvant treatment of colon cancer. The 6-year survival analysis of the landmark MOSAIC study presented at the American Society of Clinical Oncology meeting in 2007 showed that FOLFOX significantly improved the overall survival in Stage III colon cancer surgically resected. In May 2008, following the publication of the final results of the study, the FDA approved the inclusion of six-year Overall Survival analysis and five-year Disease Free Survival data for stage III colon cancer patients treated following surgery to remove the primary tumor in the Eloxatine(R) Prescribing Information.
FOLFOX is now the standard treatment for stage III colon cancer patients who have undergone complete resection of the primary tumor.
Following the end of the Eloxatine(R) European regulatory data exclusivity in April 2006, a number of oxaliplatin generics have received marketing authorization and have now been launched throughout Europe.
Eloxatine(R) is in-licensed from Debiopharm and is marketed in more than 70 countries worldwide. The three leading countries in for sales of Eloxatine(R) in 2008 were the United States, France and Canada (source: IMS, 2008 sales).
【2007】
Eloxatin(R)は、米国で術後療法および転移結腸直腸がん治療薬として市場トップの位置付けを確保し、第4四半期に12.4%増の2億3,600万ユーロの純売上高を記録しました。ヨーロッパでは、引き続き同製品のジェネリック医薬品が発売されており、第4四半期の売上高は36.3%減の7,900万ユーロとなりました。「その他」の国でのEloxatin(R)の純売上高は、19.0%増の5,000万ユーロでした。【2006】
FDAは、米国におけるEloxatin(R)の小児への適応拡大を承認し、他の規制面の独占期間と同様に、データ保護期間を2007年2月まで6カ月間延長しました。
第4四半期におけるヨーロッパでのEloxatin(R)の純売上高は、ドイツおよびイギリスでジェネリック医薬品が発売されたことにより、11.4%減の1億2,400万ユーロとなりました。●Campto (irinotecan) 【2008】 【2007】 【2003】 -France (rank: #2,シェア34.2%), Italy (rank: #2,シェア33.4%) and Germany (rank: #2,シェア31.8%). 北米、南米、日本では未発売 ・進行性大腸癌に用いる。 5-fluorouracil (FU) and folinic acid (FA)との併用がfirst-line treatment 単独投与がsecond-line treatment ・Phase III studiesが複数並行して実施。 進行性胃癌、小細胞肺癌、非小細胞肺癌 ・Aventisはヤクルト本社からのライセンスで1995年に初めて発売。 Europe, Asia and Africa.●Cabazitaxel (Jevtana ー Sanofi-Aventis) 前立腺癌 【2009】
Cabazitaxel (taxoid, prostate cancer; Phase III). Cabazitaxel is a new taxane derivative. A Phase III study in hormone resistant prostate cancer after failure of Taxotere® was successfully completed in 2009 and regulatory submissions are planned in the first half of 2010. The FDA has granted Fast Track Designation for this indication;●rimonabant（商品名Acomplia） 抗肥満薬 【2008】
第4 四半期に市場から撤退したAcomplia(R)は、2008 年に合計7,200 万ユーロの純売上高を記録しました。Acomplia(R) (rimonabant) is a selective CB-1 receptor blocker developed in the treatment of obese or overweight patients with associated cardiometabolic risk factors such as type 2 diabetes or dyslipidemia. It had been marketed in Europe and in certain other countries, but in 2008 was withdrawn from all selling and marketing.
In October 2008, the European Medicines Agency (EMEA) recommended the temporary suspension of the marketing authorization of Acomplia(R) for the approved indication of overweight and obese patients. Sanofiaventis subsequently definitively stopped selling and marketing Acomplia(R) in all countries concerned. The Group has filed to withdraw marketing authorizations worldwide, and in January 2009, the European Union withdrew the marketing authorization.
【2007】
Acomplia(R)の純売上高は、第4四半期に2,100万ユーロ、通年で7,900万ユーロとなりました。 11月に、欧州委員会は、2型糖尿病に関する治験結果をヨーロッパの添付文書（セクション5.1）に含めるというAcomplia(R)に関する欧州医薬品審査庁（EMEA）の肯定的意見を採択しました。この決定は、該当症状の薬物療法を受けていない2型糖尿病患者の血糖値管理におけるAcomplia(R)を評価する初の治験であるSERENADEスタディに基づいて判断されました。【2006】
米国で進行中のrimonabantの審査に関し、サノフィ･アベンティスは、2006年2月17日にFDAから受領した承認見込み通知に対する完全な回答書を2006年10月26日に提出しました。FDAは、これを完全なクラス2の回答書として受理し、ユーザーフィーの目標日を2007年4月26日に設定しました。
AcompliaRは、イギリス（2006年6月末）、デンマーク（8月）、ドイツ、アイルランド、ノルウェー、フィンランド（9月）、オーストリア、アルゼンチン（10月）、スウェーデン（11月）、ギリシャ（12月）で販売されています。第4四半期の純売上高は2,000万ユーロ、通年の純売上高は3,100万ユーロでした。同製品は、2007年1月にチリおよびメキシコで発売されました。
Acomplia(R)は、心血管代謝リスク因子を持つ肥満患者を治療している専門医や一般開業医から非常に肯定的に受け止められました。
2007年1月12日、ドイツ保健省は、Acomplia(R)を「快適性向上」または「生活改善」薬として分類し、ドイツの強制健康保険制度における償還の対象から除外するという連邦共同委員会（「G-BA」）の勧告を批准する決定を発表しました。
サノフィ･アベンティスは、同薬のプロファイルを考えてこの分類は不当であると考え、裁判で異議を申し立てています。2006年12月5日、南アフリカ・ケープタウンで開催された国際糖尿病連合（International Diabetes Federation）の国際糖尿病学会議（World Diabetes Congress）で、SERENADEスタディの結果が発表されました。SERENADEスタディの結果により、現在、糖尿病治療薬による治療を受けていない2型糖尿病患者において、rimonabantを投与された患者では、プラセボと比較すると、血糖値管理と体重に加え、HDLコレステロール（善玉コレステロール）やトリグリセリド（中性脂肪）など、その他のリスク因子も改善することが示されました。SERENADEは、2型糖尿病患者において、rimonabantによって血糖値管理が有意に改善することを示すためにRIO-DIABETESに続いて実施されている2つ目のスタディです。
SERENADEに関する書類は、2006年12月にヨーロッパ保健当局に提出されました。■糖尿病 ●Lantus (insulin glargine) A basal (long-acting) insulin 【2009】
世界トップクラスのインスリンブランドであるLantus®（ランタス）は、第4 四半期に16.7%増の7 億6,300 万ユーロの純売上高を記録しました。米国では、SoloSTAR®（ソロスター）インスリンペン型注入器製剤の利用拡大に牽引され、16.8%増の4 億6,000万ユーロと堅調な成長を達成しました。「その他」の国では、純売上高は36.7%増の1 億400 万ユーロでした。ヨーロッパでは、ドイツでの不調にもかかわらず、8.4%増の1 億9,900 万ユーロの純売上高を記録しました。通年では、SoloSTAR®（ソロスター）インスリンペン型注入器製剤の世界売上高が22.5%増の30 億8,000 万ユーロとなり、Lantus®（ランタス）は、連結純売上高で見てグループ中で最も売れている製品となりました。米国では、12 月末時点（2009 年12 月IMS NPA）で、Lantus®（ランタス）の新規処方に対するSoloSTAR®（ソロスター）インスリンペン型注入器製剤の貢献度が26.4%（前年同期比6.7 ポイント増）に達しました2009 年に、Lantus®（ランタス）やApidra®（アピドラ）を投与するための新しいカートリッジ交換型のペン型注入器ClikSTAR®がヨーロッパの一部の国とカナダで発売されました。ClikSTAR®とSoloSTAR®（ソロスター）により、サノフィ･アベンティスは、患者さんのインスリン治療において使いやすいペン型注入器を幅広く提供できるようになりました。ClikSTAR®は現在、米国食品医薬品局（FDA：Food and Drug Administration）の承認審査中です。【2008】
世界トップクラスのインスリンブランドであるLantus(R)（ランタス）は、2008 年度のグループ売上高の増加に最も貢献しました。
この製品は、3 つの地域すべてにおいて堅調な成長を記録しました（米国30.8%、ヨーロッパ16.3%、「その他」の国 46.2%）。新世代のLantus(R)SoloSTAR(R)（ランタスソロスター）インスリン注入器は、米国での売上増に大きく貢献しました。 当社の目標は、Lantus(R)（ランタス）を製品価値で世界一の抗糖尿病薬として確立することです。【2007】
Lantus(R)（ランタス）は、20億ユーロを超える売上高（20億3,100万ユーロ）を達成した世界初のインスリンブランドです。第4四半期に、同製品は3つの地域すべてにおいて堅調な成長を記録しました。Lantus(R)（ランタス）の投与に使用する新型のSoloSTARR使い捨てペン型注入器は現在、大部分のヨーロッパ諸国と米国で提供されています。
アメリカ心臓学協会（AHA：American Heart Association）の2007年学術会議において、2万人以上の2型糖尿病患者の医療費請求についてレトロスペクティブ解析を行った調査の結果が発表されましたが、この調査結果から、インスリン グラルギン（Lantus(R)）によるインスリン療法を開始すると、NPHインスリンによる治療と比較して、その後の心筋梗塞（MI）発症率が低下することが判明しました。Lantus(R) (insulin glargine) is a long-acting basal insulin analog, offering improved pharmacokinetic and pharmacodynamic profiles compared to other basal insulins. Lantus(R) is indicated for once-daily subcutaneous administration in the treatment of adult patients with type 2 diabetes mellitus (T2DM), who require basal insulin for the control of hyperglycemia, and for adult and pediatric patients aged six years and above with type 1 diabetes mellitus (T1DM).
Lantus(R) can be administered subcutaneously thanks to syringes or specific pens including Lantus(R) SoloSTAR(R). Lantus(R) SoloSTAR(R) is a pre-filled disposable pen available in over 50 countries worldwide. It is the only disposable pen that combines the following advantages; a low injection force, up to 80 units per injection and ease-of-use. In 2007, it was awarded a GOOD DESIGNmV Award by the Chicago Athenaeum Museum of Architecture and Design.
Lantus(R), the number-one prescribed insulin in the world in both sales and units (source: IMS, 2008 sales), is the only once-daily, 24-hour duration of action, peakless basal insulin.
The uniqueness of the Lantus(R) profile was confirmed in a direct comparison to detemir, another basal insulin analog, where Lantus(R) was shown to have activity levels more than 4 times greater than detemir during the period from 12 to 24 hours after administration. The same study showed a marked and highly significant difference in terms of duration of action: Lantus(R) showed a 24-hour coverage whereas detemir had a duration of action of only 17.5 hours. Indeed, a large clinical study confirmed that, while Lantus(R) is effective once a day, 55% of patients need detemir twice daily. Moreover, in this study Lantus(R) patients used a 40% smaller dose and had 3 times fewer injection site reactions.
The Lantus(R) profile allows a once-daily regimen that can be taken at any time (albeit at the same time every day) with titration under safer conditions and less hypoglycemia than with the basal human insulin NPH. Patients can titrate Lantus(R) easily and safely toward Fasting Plasma Glucose target thanks to the Lantus(R) profile. The results in terms of glycemic control are particularly consistent with Lantus(R) given once-a-day and properly titrated: e.g., the final mean A1C (HbA1c, a measure indicating good control of long-term blood sugar levels) on Lantus(R) ranged from 6.9% to 7.2% in seven studies where aggressive titration was performed and strict monitoring was used.
In 2008, the American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) released the updated treatment recommendations for type 2 diabetes. Designed by a team of diabetes experts, the updated recommendations provide healthcare professionals with a consensus algorithm that further establishes basal insulins such as Lantus(R), or a sulfonylurea such as Amaryl(R), as two preferred second-line treatment options for people with diabetes who are unable to achieve glycemic control targets with lifestyle intervention and metformin alone. These new treatment recommendations reinforce the timely use of basal insulin as a “Core Therapy” for type 2 Diabetes.
A number of controlled and randomized studies have investigated the efficacy and safety of Lantus(R) plus oral antidiabetic agents (OADs) in type 2 diabetes mellitus:
kﾎ The recently published TULIP study demonstrated the advantage of prescribing Lantus(R) as soon as patients’ glycemic targets are not achieved with diet, exercise and oral medications alone, bringing them below the recommended glycemic goal of 7%;
kﾎ A recent meta-analysis of 5 studies comparing Lantus(R) to NPH, confirmed a lower rate of all nocturnal hypoglycemia including severe hypoglycemia with Lantus(R) as compared to NPH in patients with type 2 diabetes;
kﾎ The APOLLO study published in 2008 in The Lancet compared two strategies for insulin initiation in patients with type 2 diabetes after OAD failure: a prandial versus a basal insulin strategy with Lantus(R).
APOLLO showed that after OAD failure in type 2 patients Lantus(R) reduces A1C to target with fewer hypoglycemic events, fewer injections and blood glucose monitoring than with a prandial insulin strategy;
kﾎ The INITIATE study showed that Lantus(R) is an easy and effective method of insulin initiation in patients with type 2 diabetes on OADs. In this study, within 24 weeks, Lantus(R) lowered A1C by 2% to reach a mean A1C of 6.8-6.9% with a concomitant treatment satisfaction improvement;
kﾎ The SCHREIBER study, an observational study of everyday practice conducted in more than 12,000 patients, showed that Lantus(R), when added to oral diabetes medications, brings the patients to a target A1C of 7.0% after an average 9-month period. This glycemic control is sustained in the long term, 32 months after Lantus(R) initiation. In addition, the neutral effect on weight observed at 9 months was confirmed at 32 months; and
kﾎ The GINGER study demonstrated the superiority of a basal bolus regimen with Lantus(R) and Apidra(R) to a premixed insulin regimen in terms of blood glucose control with no excess in hypoglycaemia rate in a population of advanced type 2 diabetes patients.Several studies presented in 2008 demonstrated the advantages of Lantus(R) in a real-life setting compared to other basal insulins:
kﾎ Lantus(R) is more effective at lowering A1C than detemir and provides cost savings (THIN Study);
kﾎ Lantus(R) is more effective at lowering A1C, results in a lower rate of hypoglycemia, and reduces total healthcare cost compared to NPH (ROLE Study);
kﾎ Lantus(R) results in better patient satisfaction than NPH (LIVE-DE Study); and
kﾎ Patients who failed to achieve glycemic goals on NPH significantly improve their A1C after they are switched to Lantus(R). They also had less hypoglycemia and improved treatment satisfaction (LAUREL Spain).Sanofi-aventis has set up a comprehensive clinical program to evaluate the acute and long-term effect of Lantus(R) on cardiovascular outcomes. As part of this program, the INTENSIVE trial in patients with STEMI and the ORIGIN morbidity/mortality trial in high-risk dysglycemic patients are still ongoing and results are expected in 2012.
Lantus(R) is available in over 70 countries worldwide.
The three leading countries for sales of Lantus(R) in 2008 are the United States, Germany and France (source: IMS 2008 sales).
【2006】
世界トップクラスのインスリンブランドであるLantus(R)（ランタス）は、第4四半期も優れた業績を収め、純売上高は35.8%増の4億5,100万ユーロとなりました。2006年度における同製品の純売上高は、36.9%増の16億6,600万ユーロに達しました。2006年9月に、新型の使い捨てペンSolostar(R)がヨーロッパで承認され、現在、米国で申請審査を受けています。 Solostar(R)は、2006年度最終四半期に初めて発売されました。[2003] ・１日１回 basal (long-acting) insulinを必要とする成人２型糖尿病患者 および１型小児糖尿病患者に用いる。 ・遅効型で２４時間安定した持続効果 ・2003.3 EUで６才以上の児童での使用を認可。 ・2003.5 FDAは１型・２型糖尿病患者での随時使用を認可。 （EUは2002.12に認可済み） ・Diabetes Care 2003.11月号で重要なデータ報告 The Treat to Target trialの結果では、Lantus投与患者の25%以上がA1Cが７％以下を達成。 ・2003年, Lantusは世界４０か国以上で発売。 ～France, Italy, India, Latin America, Russia, South Africa, Sweden and Switzerland. 日本では承認2003.10、発売2003.12 米国とドイツでインスリンアナログ製剤のトップを達成。 [2002] ・米国承認2000.4、EU承認2000.6 ・2002.6 FDAとEUに１型・２型糖尿病患者での随時使用を申請。 [2000] 2000年末 ドイツで発売●Amaryl (glimepiride) 【2009】 【2008】
Amaryl(R) (glimepiride) is a latest-generation, orally administered once-daily sulfonylurea (a glucoselowering agent) indicated as an adjunct to diet and exercise to improve glycaemic control in patients with type 2 diabetes. Amaryl(R) reduces the body’s blood sugar level in two ways: by helping the body to produce more insulin both at mealtime and between meals and by decreasing insulin resistance. Amaryl(R) has a more rapid onset and longer duration of action than first-generation agents, allowing patients to achieve a very good level of control with a lower risk of hypoglycemia.Amaryl(R) was the first oral diabetes drug in its class to receive approval for administration in one of three ways: either as a monotherapy or in combination with insulin or metformin.
The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) recommendations for type 2 diabetes were updated in 2008: they further establish the combination of metformin and second generation sulfonylureas such as Amaryl(R) as a one of the two preferred second-line treatment options for people with diabetes who are unable to achieve glycemic control targets with lifestyle intervention and metformin alone. The second recommanded option is to add to metformin a basal insulin, such as Lantus(R).
The combination of metformin (which reduces hepatic glucose production and improves insulin resistance) with a sulfonylurea (which stimulates insulin secretion) is the rational combination for counteracting the two defects seen in type 2 diabetes. It is the most prescribed combination of diabetes drugs worldwide. Amaryl M(R), a fixed-dose combination of glimepiride plus metformin in a single presentation was launched in 2007. The fixed dose treatment is more efficacious than either agent alone in patients with type 2 diabetes and has equal efficacy and better compliance than the free combination of glimepiride and metformin. In 2008, Amaryl M(R) was launched in India, Mexico and Brazil among other countries.
Our leading market for Amaryl(R) is Japan, where it is the leading oral antidiabetes product by volume (source: IMS 2008 sales).
【2007】 【2003】 - Germany (rank: #1,シェア25%), 米国(rank: #6,シェア4.4%) and Japan (rank: #3,シェア9.7%). ・新世代スルホニル尿素剤で、１日１回投与。 インスリン産生を促進。 低血糖リスクや体重増加が少ない。
●Apidra®（アピドラ）超速効型インスリンアナログ 【2009】
超速効型インスリンアナログであるApidra®（アピドラ）の第4 四半期の純売上高は、30.0%増の3,700 万ユーロでした。通年の売上高は、2009 年に米国でApidra®SoloSTAR®（アピドラ注ソロスター）インスリンペン型注入器製剤が発売されたことにより、38.8%増の1 億3,700 万ユーロとなりました。●Insuman (human insulin) 【2008】 【2007】 【2003】 - シェアare Germany (21.5%), Austria (11.9%) and France (3.7%). 米国はAventisは販売しない。 ・体内産生インスリンと同一の生合成インスリン。 ・西欧・東欧・ラテンアメリカで販売されている。 [2002] ・最初の発売はドイツ1999.4、他にオーストリア等１３カ国で販売■リウマチ・骨粗鬆症 ●Actonel(R)/Optinate(R)/Acrel(R) (risedronate sodium) 【2008】
Actonel(R) (risedronate sodium) belongs to the bisphosphonate class. The bisphosphonates are antiresorptive treatments that inhibit osteoclast-mediated bone resorption and therefore help to prevent osteoporotic fractures.Actonel(R) is the only osteoporosis treatment that reduces the risk of vertebral fracture and non-vertebral fractures in just six months. Actonel(R) also provides reduced risk of fracture at all key osteoporotic sites: vertebral, hip and non-vertebral sites studied as a composite endpoint (hip, wrist, humerus, clavicle, leg and pelvis).
Actonel(R) is available in various formulations (tablets and sachets) and dosages to better fit patients’ needs:
Actonel(R) 5 mg daily is indicated for the prevention of postmenopausal osteoporosis (PMO) in Europe and for the treatment of PMO and glucocorticoid-induced osteoporosis in Europe and the United States. In the United States, it is indicated for patients either initiating or continuing systemic glucocorticoid treatment (daily dosage of 7.5 mg or more of prednisone or equivalent) for chronic diseases.
Actonel(R) 35 mg once-a-week is indicated for treatment of this disease and for treatment of osteoporosis in men in both Europe and the United States, and for prevention of PMO in the United States.
Actonel(R) 30 mg is approved for the treatment of Paget’s disease, a rare bone disorder.
Actonel(R) 75 mg, already available in the United States, was launched in France and Italy in September 2008. Actonel(R) 75 mg is a monthly treatment dosed on two consecutive days during the month, for the treatment of PMO.
Actonel(R) 150 mg was launched in the United States in June 2008 for the treatment of PMO. Recent year-2 results confirmed that 150 mg Actonel(R) given once-a-month was overall similar to 5 mg daily Actonel(R) in both efficacy and safety/tolerability when used in the treatment of postmenopausal osteoporosis.
Actonelcombi(R), the combination of Actonel(R) 35 mg and calcium/vitamin D pouch form was launched in France in January 2008.
Actonel(R) is in-licensed from Procter & Gamble Pharmaceuticals (P&G). It is marketed by sanofiaventis and P&G in more than 75 countries through the “Alliance for Better Bone Health”. Additional details on this alliance can be found in “kﾀ Alliances” below. In Japan, Actonel(R) is marketed by Eisai.
The top four markets for Actonel(R) are the United States, France, Canada and Spain (source: IMS, 2008 sales, all available channels).
【2007】 【2006】
Actonel(R) (risedronate sodium) belongs to the bisphosphonate class. The bisphosphonates are antiresorptive treatments that inhibit osteoclast-mediated bone resorption and therefore help to prevent osteoporotic fractures.
Actonel(R) 5mg daily is indicated for the prevention of postmenopausal osteoporosis (PMO) in Europe and for the treatment of PMO and glucocorticoid-induced osteoporosis in Europe and the United States. In the United States, it is indicated for patients either initiating or continuing systemic glucocorticoid treatment (daily dosage of 7.5mg or more of prednisone or equivalent) for chronic diseases.
Actonel(R) 35mg once-a-week is indicated for treatment of this disease and for treatment of osteoporosis in men in both Europe and the United States, and for prevention of PMO in the United States.
Actonel(R) 30mg is approved for the treatment of Paget's disease, a rare bone disorder.
Actonel(R) is the only osteoporosis treatment that reduces the risk of vertebral fracture and non-vertebral fractures in just six months (Roux & al.). Actonel(R) also provides fractures risk reduction at all key osteoporotic sites: vertebral, hip and non-vertebral studied as a composite endpoint (hip, wrist, humerus, clavicle, leg and pelvis) (Harris & al. . McClung & al.).
A recent retrospective cohort study (Silverman & al., Osteoporosis Int.) showed that during the first year of treatment, patients treated with Actonel(R) weekly decreased their risk of hip fracture by 46% at 6 months and by 43% at 12 months compared to patients treated with alendronate weekly. These data confirmed the early onset of action (as early as 6 months) of Actonel(R).
Actonel(R) is in-licensed from Procter & Gamble Pharmaceuticals (P&G) and is co-marketed by sanofiaventis and P&G through the “Alliance for Better Bone Health”. In Japan, Actonel(R) was previously marketed by sanofi-aventis under a license from Ajinomoto. As of October 2005, with the agreement of Ajinomoto, distribution of Actonel(R) in Japan was transferred to Eisai.
The top four markets for Actonel(R) are the United States, France, Canada and Spain (source : full year 2006 net sales, all available channels except Spain, retail only).
Actonel(R). We co-market Actonel(R) with Procter & Gamble Pharmaceuticals, which holds the NDA and the patents for this product in the United States. The U.S. patent on the active ingredient expires in December 2013, and a number of other patents having expiration dates ranging through 2018 cover this product. In Europe, the compound patent has expired in some national markets, but remains in force through December 2010 in a number of countries including France, Germany, the United Kingdom, and Italy. Additional patent coverage in Europe is provided by formulation patents with expiration dates in 2012 and 2018 as well as a process patent.
[Procter & Gamble Pharmaceuticals (P&G)]
We in-license Actonel(R) from P&G. An alliance with P&G was concluded in April 1997 for the co-development and marketing of Actonel(R). The 1997 agreements were amended in October 2004 following the acquisition of Aventis by sanofi-aventis. The alliance agreement with P&G includes the development and marketing arrangements for Actonel(R) worldwide (except Japan). The ongoing R&D costs for the product are shared equally between the parties, while the marketing arrangements vary depending on the country in which the product is marketed.
Under the alliance arrangements with P&G, there are four principal territories with different marketing arrangements:
・co-promotion territory: the product is jointly marketed through the alliance arrangements under the brand name Actonel(R) with sales booked by P&G. The co-promotion territory includes the United States, Canada, France, Germany, the Netherlands, Belgium and Luxemburg;
・secondary co-promotion territory: the product is jointly marketed through the alliance arrangements under the brand name Actonel(R) with sales booked by sanofi-aventis. The secondary co-promotion territory includes the United Kingdom, Ireland, Sweden, Finland, Greece, Switzerland, Austria, Portugal and Australia. P&G may also at a later date exercise an option to co-promote the product in Denmark, Norway, Mexico and/or Brazil;
・co-marketing territory: each company markets the products independently under its own brand name. This territory currently includes Italy and Spain. In Italy the product is sold under the brand name Actonel(R) by P&G and under the brand name Optinate(R) by sanofi-aventis; in Spain under the brand name Acrel(R) by P&G and under the brand name Actonel(R) by sanofi-aventis;
・sanofi-aventis only territory: the product is marketed by sanofi-aventis independently under the brand name Actonel(R) or another agreed trademark in all other territories.
[2003] - The top three markets for Actonel are the U.S., France and Canada. ・Procter & Gamble Pharmaceuticalsと共同販売 ・第三世代bisphosphonate ・骨再吸収阻害作用により骨損失予防。 ・Actonel - 週１回35mg 及び１日１回 5mg投与 閉経後骨粗鬆症の予防と治療、慢性疾患の全身性glucocorticoid誘発性骨粗鬆症の治療 Actonelはまた、稀少骨疾患 Paget's disease治療も適応。 ・Actonelは、速効性ならびに骨破損保護を１年以内に提供するという唯一の骨粗鬆症治療薬。 ・ENDO 2003で発表された長期臨床研究によると、Actonelは７年間の治療で、新たな 椎骨破損の発生が低い。 [2002] ・2002.5 - FDAは、閉経後骨粗鬆症の予防と治療に、週１回35mg投与を承認。 これは2002.7 スエーデンでも認可(EU相互認証)。 [2000] ・2000.中 Actonelが米国発売、Procter & Gambleと共同販売。●Arava (leflunomide) 【2008】 【2007】 【2003】 - Our largest markets for Arava are the U.S. and Germany. ・世界７０カ国で販売。 米国発売1998、欧州発売1999、日本発売2003.9 ・経口disease-modifying anti-rheumatic drug (DMARD) 活動性RA成人患者で、X線像による骨の構造破壊および関節間隙狭化を抑制し、身体機能を改善した。 ・Aravaは１日１回経口投与。 早期・慢性関節リウマチに用いる。 ・[日本]アラバ錠10mg／アラバ錠20mg／アラバ錠100mg 製造販売(輸入)／サノフィ・アベンティス株式会社 [効能効果]関節リウマチ [用法及び用量] 通常、成人にはレフルノミドとして１日１回100mg錠１錠の３日間経口投与から開始し、 その後、維持量として１日１回20mgを経口投与する。なお、維持量は、症状、体重により 適宜１日１回10mgに減量する。 [副作用] 本剤の承認時までの副作用発現状況は以下の通りである。 国内における臨床試験での安全性評価対象症例365例中248例（68.0％）に副作用（臨床検 査値異常を含む）が認められた。主な副作用は、肝機能検査値異常68例（18.6％）、下痢 39例（10.7％）、脱毛症39例（10.7％）、尿沈渣異常35例（9.6％）、発疹33例（9.0％）、 高血圧30例（8.2％）、上気道感染29例（8.0％）、腹痛24例（6.6％）、尿蛋白19例（5.2％）等であった。 また、海外における臨床試験での安全性評価対象症例1339例中801例（59.8％）に副作用 （臨床検査値異常を含む）が認められた。主な副作用は、下痢186例（13.9％）、脱毛症1 30例（9.7％）、嘔気106例（7.9％）、腹痛99例（7.4％）、発疹91例（6.8％）、肝機能 検査値異常67例（5.0％）、頭痛65例（4.9％）、高血圧61例（4.6％）であった。なお、 これらの副作用は早期（投与開始後８週間以内）にあらわれる傾向があり、軽度又は中等 度でかつ可逆的であることが多かったが、観察を十分に行うこと。■抗感染症 ●Ketek (telithromycin) 【2008】 【2007】 【2003】 ・ketolides系抗生物質として最初の新薬。 ・耐性菌を含む上気道・下気道感染症に有効なようにデザイン。 ・Ketekは、最初に、ドイツ発売2001.10。 主要EU、ラテンアメリカで承認。 既に世界で500万人が使用。 ・2003年後半、Canada, Turkey and Japan (藤沢薬品にoutlicensed)で承認・発売。 トルコでは経口剤トップ(IMS Retail Sales Audit November 2003) フランスでトップクラス(GERS Retail Sales Audit November 2003). ・2003.1 FDAがapprovable letterを発行(追加臨床試験の要求はなし) 適応は、慢性気管支炎の急性憎悪、急性細菌性鼻炎、市中肺炎 2003.10 Aventisが必要資料を提出したので、FDAは６か月以内に回答予定。 [2002] ・2002.7 FDAに再申請。 これは2001年のapprovable letterが安全性追加データを 要請したいたものに対応。2.4万人のデータ添付。●Targocid (teicoplanin) 【2008】 【2007】 【2003】 - Italy (rank: #1,シェア86.4%), Japan (rank: #3,シェア17%) and the UK (rank: #1,シェア62%). ・注射用glycopeptide系抗生物質。 グラム陽性菌による重篤なstaphylococcal感染症 (PC,セフェム等耐性菌を含む)が適応。 ・2003, Targocidは日本で小児への使用が認可。●Tavanic (levofloxacin) 【2008】 【2007】 【2003】 ・経口・静注の広範囲fluoroquinolone、第一製薬からライセンス ・１日１回投与で速効性。 ・適応は、慢性気管支炎の急性憎悪、急性細菌性鼻炎、市中肺炎、複雑性尿路感染、 皮膚・軟部組織感染。 ・2003, Tavanicは英国承認(EU Mutual Recognition State) －非複雑性尿路感染■中枢神経系 ●Ambien/Stilnox(zolpidem) 睡眠薬 【2008】
第4 四半期における催眠薬Ambien CR(R)およびAmbien(R) IR の米国での純売上高は、それぞれ1 億7,000 万ドル、2,400 万ドルでした。通年におけるAmbien CR(R)の純売上高は6 億8,100 万ドル、Ambien(R) IR の純売上高は1 億2,500 万ドルでした。日本では、市場トップクラスの睡眠薬であるMyslee(R)（マイスリー）が、第4 四半期に17.8%増（4,900 万ユ ーロ）、通年に14.9%増（1 億4,200 万ユーロ）の純売上高（2008 年1 月1 日以降サノフィ･アベンティスに連結）を記録 し、堅調な業績を達成しました。Stilnox(R) (zolpidem tartrate) is the leading hypnotic worldwide and is indicated in the short-term treatment of insomnia.
Stilnox(R) is available in 5 mg and 10 mg tablets. Stilnox(R) rapidly induces sleep that is qualitatively close to natural sleep and devoid of certain side effects that are characteristic of the benzodiazepine class as a whole. Its action lasts for a minimum of six hours, and it is generally well tolerated, allowing the patient to awake with a reduced risk of impaired attention, decreased alertness or memory lapses throughout the day. The risk of dependence is minimal when Stilnox(R) is used at the recommended dosage and duration of use. Stilnox(R) is currently the only hypnotic demonstrated to be suitable for “as needed” use based on an extensive program of eight clinical trials, which together enrolled over 6,000 patients. This mode of administration avoids the systematic intake of a hypnotic by patients who suffer only occasionally from insomnia.
We have developed a controlled release formulation of zolpidem tartrate, sold in the United States under the brand name Ambien(R) CR in 6.25 mg and 12.5 mg tablets.Stilnox(R) is marketed in over 100 countries. It was launched in Japan under the brand name Myslee(R) in December 2000 and became the leading hypnotic on the market within three years of its launch. Myslee(R) has been copromoted jointly with Astellas since 2006. We launched Ambien(R) CR in the United Sates in September 2005.
The top three markets for Stilnox(R) (both immediate and controlled release formulations) are the United States, Japan and Italy (based on 2008 net sales).
Generic zolpidem tartrate has been available in France since 2004. In the United States, generics of the immediate release formulation of Ambien(R) have been available since 2007.
【2007】
米国におけるAmbien CR(TM)の純売上高は、第4四半期に1億9,000万ドル、通年では7億5,100万ドルに達しました。
2007年4月20日に米国での特許保護が満了したAmbien(R) IRの純売上高は、前年同期の3億5,200万ユーロに対し、第4四半期には3,000万ユーロとなりました。通年のAmbien(R) IRの純売上高は5億3,800万ドルでした。
日本では、第4四半期におけるMyslee(R)（マイスリー）サノフィ･アベンティスに非連結）の売上高が6.4%増の3,400万ユーロに達しました。2007年度通年における同製品の売上高は、9.8%増の1億1,800万ユーロとなりました。
サノフィ･アベンティスは、アステラス製薬株式会社との契約条件に基づき、2008年1月1日より、日本におけるMyslee(R)（マイスリー）の純売上高を連結します。【2006】
第4四半期における米国でのAmbien(R)（マイスリー）/Ambien CR.の純売上高は、47.8%増の5億3,200万ユーロとなりました。同製品の市場シェアは、9月時点での45.2%（IMS NPA-3チャンネル－2006年9月）に対し、12月時点で46.2%9となりました。12月末時点で、Ambien CR.の処方数は、AmbienRブランド製品の処方数全体（IMS NPA小売および通信販売）の31.8%を占めました。
2006年11月末に、FDAはAmbien(R)（マイスリー）とAmbien CR(TM)に対し、小児への適応を認めました。この決定の効果の1つとして、Ambien(R) IRのジェネリック医薬品の発売が2007年4月まで延期されます。
日本では、2006年度にMyslee(R)（マイスリー）の売上高（全売上高）が15.7%増の1億1,900万ユーロに達しました。Thanks to its capacity to bind selectively to brain receptors responsible for hypnotic activity, Stilnox(R) rapidly induces sleep of a quality close to that of natural sleep, with a low incidence of side effects. Its action persists for at least six hours and is associated with a low risk of dependence at recommended doses and durations of treatment. Stilnox(R) is one of the most extensively studied hypnotics in the world: the data concerning its efficacy and tolerability were generated in 160 clinical studies conducted on a total of approximately 80,000 patients throughout the world. It is currently the only hypnotic that has been proved, in a program comprising eight studies with a total enrollment of approximately 6,000 patients, to be suitable for an “as needed” administration, i.e. discontinuous use. This mode of administration presents considerable advantages for people with occasional insomnia. Two studies have demonstrated that Zolpidem MR (modified release formulation) improves the sleep maintenance during the second part of the night, ensuring high-quality sleep throughout the night. This formulation was launched in the U.S. under the name Ambien CR. in September 2005. In Japan, a clinical development program, the results of which are expected in 2008, is currently ongoing.●Copaxone (glatiramer acetate) 多発性硬化症治療薬 【2009】
2008 年4 月1 日に北米でサノフィ･アベンティスによる販売を終了したことにより、この製品の連結純売上高は2009 年度通年に23.8%減少しました。北米でのCopaxone®の売上に対してサノフィ･アベンティスが取得するロイヤリティは、2010 年度第1 四半期末で終了します。【2008】
Copaxone(R) (glatiramer acetate) is an immunomodulating agent indicated for reducing the frequency of relapses in patients with relapsing-remitting multiple sclerosis. Copaxone(R) is available as a self-injectable pre-filled syringe storable at room temperature for up to one month. This formulation allows improved product delivery, increased patient comfort and convenient transportation and storage.This disease-modifying drug is characterized by an original and specific mode of action on multiple sclerosis. Clinical studies have shown that Copaxone(R) is more effective than placebo at two years, but also that it has a clinical efficacy over 15 years both in reducing relapses and progression of disability. A significant effect on lesions has also been confirmed by nuclear magnetic resonance imaging.
Recent results of the PreCISe study have demonstrated that Copaxone(R) reduces the risk of developing confirmed multiple sclerosis in patients having Clinical Isolated Syndrome (CIS) by 45% as compared to a placebo. In February 2009 the Medicines and Healthcare products Regulatory Agency (MHRA) approved an expanded label for Copaxone(R) to include the treatment of patients with CIS suggestive of multiple sclerosis (MS). This approval includes 24 EU member countries that take part in the MHRA “mutual recognition procedure”. Applications have been submitted to national Health Authorities of other European countries, including France and Switzerland. Approval of an expanded label for Copaxone(R) to include the treatment of CIS patients was also provided by the Australian Health Authority (the Therapeutic Goods Administration) in December 2008.
The three leading countries for Copaxone(R) are the United States, Germany, and France (based on 2008 net sales).
Copaxone(R) is in-licensed from Teva and marketed via our agreement with that company. Teva assumed the Copaxone(R) business, including sales of the product in the United States and Canada, on March 31, 2008. Under the terms of our agreement, the Copaxone(R) business in other countries will be transferred to Teva over a period running from Q4 2009 to Q1 2012 at the latest, depending on the country. Additional details on this agreement can be found in “kﾀ Alliances” below.
【2007】 【2003】 ・多発性硬化症の再発頻度を低減する効果を持つ最初の非インターフェロン剤 これまで６万人の患者に使用。 ・欧州とオーストラリアはAventisとTeva Pharmaceutical Industries Ltd.が共同販売 米国はTevaがマーケティングと販売、Aventisが流通(契約期限2008.3)、契約期限後はTevaが単独販売。●Depakine(R) (sodium valproate) 【2008】
Depakine(R) (sodium valproate) is a broad-spectrum anti-epileptic that has been prescribed for more than 40 years. Numerous clinical trials, as well as long years of experience have shown that it is effective for all types of epileptic seizures and epileptic syndromes, and is generally well tolerated. Consequently, Depakine(R) remains a reference treatment for epilepsy worldwide.Depakine(R) is also a mood stabilizer, registered in the treatment of manic episodes associated with bipolar disorder and in numerous countries in the prevention of mood episodes. Valproate is recommended as a first-line treatment in these indications by international guidelines such as the guidelines of the American Psychiatric Association, the Canadian Network for Mood and Anxiety Treatments and the U.K. NICE Guidance.
We provide a wide range of formulations of Depakine(R) which permits its adaptation to most types of patients: syrup, oral solution, injection, enteric-coated tablets, Chrono(R) (a sustained release formulation in tablets) and Chronosphere(R) (sustained release formulation of Depakine(R) packaged in stick packs, facilitating its use by children, the elderly and adults with difficulties swallowing).
Depakine(R) is marketed in over 100 countries, including the United States, where it is licensed to Abbott.
The top three markets for Depakine(R) are the United Kingdom, France and Italy (based on 2008 net sales).
【2007】 【】 ■呼吸器・アレルギー ●Allegra/Telfast (fexofenadine) アレルギー 【2009】
通年の売上高は、2.6%減の7 億3,100 万ユーロとなりました。【2008】
Allegra(R) (fexofenadine hydrochloride) is an effective, long-lasting (12- and 24-hour) non-sedating prescription antihistamine for the treatment of seasonal allergic rhinitis (hay fever) and for the treatment of uncomplicated skin manifestations of chronic idiopathic urticaria (hives). It offers patients significant relief from allergy symptoms without causing drowsiness.Allegra(R) Oral Suspension 30 mg/5 ml (6 mg/ml) was commercially launched in the United States in 2007 for the treatment of hay fever symptoms in children between the ages of 2 and 11 years and the treatment of the uncomplicated skin manifestations of hives in children aged 6 months to 11 years. Allegra(R) Orally Disintegrating Tablets (ODT), 30 mg was launched in the United States in February 2008 for use in the treatment of hay fever symptoms and uncomplicated skin manifestations of hives in children between the ages of 6 and 11 years.
We also market Allegra-D(R) 12-Hour and Allegra-D(R) 24-Hour, antihistamine/decongestant combination products with an extended-release decongestant for effective non-drowsy relief of seasonal allergy symptoms, including nasal congestion.
Allegra(R)’s largest market is Japan (based on 2008 net sales). Allegra-D(R) 12-Hour and Allegra-D(R) 24-Hour’s biggest market is the United States (based on 2008 net sales).
The single-entity formulation of Allegra(R) already faces generic competition in its major markets outside Japan. In settlement of patent litigation, Barr has been granted a license to sell a generic Allegra(R)D-12 Hours in the United States starting in November 2009.
【2007】 【2006】
米国でジェネリック３品目が2005年に出現。
By way of example, following the Group's failure to obtain a preliminary injunction halting the launch at risk of a generic version of Allegra(R) in October 2005, the Allegra(R) franchise in the United States has been substantially eroded and the asserted patent claims have still not gone to trial.Allegra(R) (fexofenadine HCl) is an effective, long-lasting (12-and 24-hour) non-sedating prescription antihistamine for the treatment of seasonal allergic rhinitis (hay fever) and for the treatment of uncomplicated skin manifestations of chronic idiopathic urticaria (hives). It offers patients significant relief from allergy symptoms without causing drowsiness.
We also market Allegra-D(R) 12 Hour and Allegra-D(R) 24 Hour, antihistamine/decongestant combination products with an extended-release decongestant for effective non-drowsy relief of seasonal allergy symptoms, including nasal congestion.
The top three markets for Allegra(R) are the United States, Japan and Australia (based on 2006 net sales).
In October 2006, the FDA approved the supplemental NDA for Allegra(R) Oral Suspension (6mg/ ml) for the treatment of seasonal allergic rhinitis symptoms in children aged 2-11 years and the treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria. Commercial launch of this product in the United States will take place prior to the 2007 spring allergy season. A 30 mg orally disintegrating tablet for pediatric use is also being developed.
In September 2005, following the first launch at risk by Barr and Teva of a generic version of fexofenadine HCL 180mg, 60mg and 30mg to compete with Allegra(R), sanofi-aventis entered into an agreement with Prasco Pharmaceuticals to launch an authorized generic of fexofenadine. For the 180mg, 60mg and 30mg fexofenadine dosage strengths, the authorized generic product, marketed by Prasco, accounted for over 40% of total prescriptions for the month of December 2006 while the Allegra(R) brand accounted for 5% for the same period (IMS NPA).Although different presentations of Allegra(R) are covered by a number of formulation, method of use and other patents including a U.S. patent claiming a particular crystalline form having expiration dates ranging through 2017, the original patent claiming Allegra(R)'s active ingredient has expired in all major markets. Notwithstanding the unexpired patents, generic fexofenadine hydrochloride tablets have been launched at risk in the United States. In Japan, Allegra(R) benefits from multiple process and formulation patents running through 2015.
[2003] - 米国(rank: #1,シェア35.4%), Japan (rank: #2,シェア16.6%), and the UK (rank: #3,シェア11%). ・Aventisのトップ品目 ・特徴 an effective, long-lasting (12- and 24-hour dosing) and powerful non-seda ting prescription antihistamine for the treatment of seasonal allergic rhinitis (SAR or hay fever) and the skin condition chronic idiopathic urticaria (CIU or hives). ・2003年Allegra 30 mg pediatric tabletsがEU相互認証により英国承認。 小児用は米国で2003.1 承認 ・Allegra-D, 持続性配合鼻閉治療薬で、効果はnon-drowsy relief of seasonal allergy symptoms, including nasal congestion. 2003.12 １日１回製剤をFDA申請 Allegra-D - 米国(rank: #1,シェア56%), Mexico (rank: #4,シェア7.6%) and Brazil (rank: #2,シェア23.9%). [2002] ・2002.11 日本で承認。 ・2000 FDAは2000年追加申請を承認。 成人に１日１回投与で季節性アレルギー鼻炎。 ６才以上の児童に１日２回投与。●Nasacort (triamcinolone acetonide) AQ Spray 【2008】
Nasacort(R)AQ Spray (NAQ) (triamcinolone acetonide) is an unscented, water-based metered-dose pump spray formulation unit containing a microcrystalline suspension of triamcinolone acetonide in an aqueous medium. First launched in 1996, NAQ is an intranasal corticosteroid, which is recommended in treatment guidelines as first-line treatment for moderate to severe allergic rhinitis patients. NAQ offers significant relief from nasal allergy symptoms to patients, with no scent, alcohol or taste.Previously indicated for the treatment of the nasal symptoms of seasonal and perennial allergic rhinitis in adults and children six years of age and older, Nasacort(R)AQ received an additional approval for the seasonal and annual treatment of pediatric patients between the ages of 2 and 5 years from the FDA in September 2008.
Our leading markets for Nasacort(R)AQ Spray are the United States, France and Turkey (based on 2008 net sales).
In settlement of patent litigation, Barr has been granted a license to sell a generic triamcinolone acetonide in the United States as early as 2011.
【2007】 【2006】
Nasacort(R) AQ Spray (NAQ) (triamcinolone acetonide) is an unscented, water-based metered-dose pump spray formulation unit containing a microcrystalline suspension of triamcinolone acetonide in an aqueous medium. It is indicated for the treatment of the nasal symptoms of seasonal and perennial allergic rhinitis in adults and children six years of age and older.
NAQ is an intranasal corticosteroid, which is recommended in treatment guidelines as first-line treatment for moderate to severe allergic rhinitis patients.
NAQ offers patients significant relief from allergy symptoms with statistically significant overall preference of sensory attributes by patients versus the market leader.
In May 2006, the HFA (hydrofluoroalkane) formulation that was slotted to launch in the United States late 2006, was terminated.
Our leading markets for Nasacort(R) AQ Spray are the United States, France and Turkey (source: 2006 net sales).
[2003]
・特徴 is an unscented, water-based metered-dose pump spray formulation unit containing a microcrystalline suspension of triamcinolone acetonide in an aqueous medium. It is indicated for the treatment of the nasal symptoms of seasonal and perennial allergic rhinitis in adults and children six years of age and older. In compliance with the Montreal Protocol to eliminate CFC-based propellant in sprays, we no longer manufacture Nasacort Nasal Inhaler. Our leading markets for Nasacort AQ Spray are
- 米国(rank: #4,シェア12.7%) and Canada (rank #3,シェア11.6%).●経口抗ヒスタミン剤のXyzal 【2009】
2010 年3 月1 日付で、サノフィ･アベンティスは、米国におけるXyzal®の全販売責任を負うことになります。【2007】
新しい処方用経口抗ヒスタミン剤のXyzal(R)は、2007年10月に米国でサノフィ･アベンティスとUCBから発売されました。第4四半期における純売上高は、800万ユーロでした。12月末時点で、Xyzal(R)は新規処方薬の5.2%を占めました（NRX IMS NPA weekly）。【】 ■泌尿器系 ●Xatral(R) /Uroxatral(R)(alfuzosin)前立腺肥大症 【2008】
Xatral(R) (alfuzosin) belongs to the class of alpha1-blockers. Capable of acting selectively on the lower urinary tract, it was the first alpha1-blocker indicated and marketed exclusively for the treatment of symptoms of benign prostatic hyperplasia (BPH). It is also the unique alpha1-blocker indicated as an adjunctive therapy with catheterization for acute urinary retention (AUR), a painful and distressing complication of BPH. Since 2003, Xatral(R) has obtained authorizations of this extension of the indication in 56 countries worldwide including 16 European countries.Xatral(R) OD (extended release formulation) is active from the first dose, provides a rapid and lasting symptom relief and improves patient quality of life.
The benefits of Xatral(R) on AUR kﾀ demonstrated with the ALFAUR study kﾀ have been confirmed by the largest international registry ever conducted on the management of AUR, Reten-World. Final results were based on 6,074 patients catheterized for AUR associated with BPH; demonstrating that a trial without catheter is now the standard of care worldwide (78% of cases) and that 86% of patients received an alpha1-blocker (Xatral(R) in seven case out of ten) at the time of catheter removal. The survey also confirmed that return to normal voiding was significantly higher in patients who received an alpha1-blocker (mainly Xatral(R)) at the time of catheter removal.
The ALTESS study had shown that Xatral(R) significantly reduced the risk of overall BPH progression.
The long term results of the ALF-ONE real life practice study were published in April 2008. The study, which enrolled some 700 patients treated with Xatral(R) over a three-year period , confirmed its efficacy and safety and showed that patients experiencing BPH progression could be rapidly identified as they are in fact not responding to Xatral(R) treatment.Lastly, Xatral(R) is the only alpha1-blocker showing no deleterious effect on ejaculation, as shown by the final results of the international ALF-LIFE trial.
The results of the Phase III clinical trial undertaken as part of the development of Xatral(R) in Japan will be discussed with the health authorities as part of a preliminary consultation in 2009.
The once-daily formulation of Xatral(R) (branded Uroxatral(R) in the United States) has been registered in over 90 countries and is marketed worldwide, with the exception of Australia and Japan.
Over four billion treatment days of alfuzosin have been prescribed worldwide since launch. The three leading countries for sales of Xatral(R) in 2008 were the United States, Italy and France (based on 2008 net sales). Generic alfuzosin became available in Italy in 2008, negatively affecting our sales there.
【2007】 【】 ● 【2008】 【2007】 【】
●Sanofi-Aventis ■Investors ●Financial publications Annual Report on Form 20-F 2010 Annual reports on Form 20-F[pdf] - Annual Results 2009 Annual report on Form 20-F 2008[pdf] 2008 Full-Year Results & Outlook 20-F 2007 sanofi-aventis[288p] 20F 2006 sanofi-aventis[2007.3.30,pdf,292p]～SEC Annual erport Annual Report 2006 Sanofi-aventis[pdf,76p] Sustainable Development Report 2006[pdf,66p] 20F 2005 sanofi-aventis[2006.3.31,pdf,277p]～SEC Annual erport ●Business Reports Annual Review 2009 Annual Review 2008 Annual Review 2007[31p] ●Archives[2004年まで] - ここには1999年以降のSanofi-Synthelabo/Aventis年次報告書有り。 20-F document 2004[2005.4.11,pdf,301p]～SEC Annual erport Annual Report 2003(Reference document) - [pdf,263p] - For Sanofi-Synthelabo ●Journalists ★Press Releases Filing of the 2010 U.S. Form 20-F and French “Document de RAmfAmrence” containing the Annual Financial Report[2011.3.1] Solid results in 2010[2011.2.9] Filing of the 2009 U.S. Form 20-F and French “Document de RAmfAmrence” and Annual Financial Report[2010.3.12] - [pdf,1p] Sanofi-aventis delivers double-digit EPS@� growth in 2009 as the Transformation program progresses[2010.2.10] - [pdf,26p] Sanofi-aventis delivers 2008 Results above Guidance[2009.2.11] - [pdf,27p] ●Drugs & products ●Your Health ～疾病別 ●Our Research ～疾病別
●Sanofi-Aventis[US]●米国サイト -http://www.sanofi-aventis.us/index.html ●Press Room Aventis Pasteur, the vaccine division of the sanofi-aventis Group, changes its name to sanofi pasteur[2005.1.10] ●Products
●サノフィ・アベンティス・ジャパン●日本 --- http://www.sanofi-aventis.co.jp/index.html 2004年8月20日、サノフィ･サンテラボがアベンティスの事業を統合し、フランス及び欧州 で第1位、世界でも第3位となる製薬企業「サノフィ･アベンティス」が誕生しました。日 本においても、サノフィ･サンテラボ株式会社とアベンティス ファーマ株式会社の両社が、 サノフィ･アベンティスグループとして、2005年1月1日より共同・協調したオペレーショ ン業務を開始。そして、2006年1月1日に法的統合を行いサノフィ･アベンティス株式会社 が誕生しました。 ●プレスリリース サノフィ・アベンティス、変革プログラムの進展に伴い、2009年度にEPSの2桁成長を達成[2010.2.18;pdf,25p] サノフィ･アベンティス、見通しを上回る2008年度業績を達成[2009.2.19;pdf,25p] 見通しを上回る2007年度利益を達成、予定配当が急増[2008.2.18] 2006年度業績発表：厳しい環境の中で特定項目を除いた調整後EPSの伸長を引き続き達成[2007.2.22,pdf,28p] ●医療従事者 ★日本の開発品パイプライン
■Sanofi-Synthelabo
http://www.sanofi-synthelabo.fr/; 2005.4.14現在http://www.sanofi-aventis.com/へ自動 ●概歴 1970 Synthelaboが、Laboratoires Dausse(1834設立)とLaboratoires Robert & Carrie re(1899設立)の合併により設立。 1973 Elf Aquitaine社はLabaz Pharmaceuticalを買収し、Sanofi社を設立。 1973 L'Oreal がSynthelabo株式の大半を取得 1974 Parcor社がSanofiにより買収 1975 SanofiがChoayに資本参加 1978 Ticlid(ticlopidine)が市販。Parcor社開発 1980 SanofiはClin Midy Industriesを買収 - SynthelaboはMetabio-Jouillieと合併 - SynthelaboはCa拮抗剤Tildiemを発売 1985 Sanofiは、Fraxiparine (nadroparine calcique)発売 1988 Synthelabo、大型商品２品目をフランス発売 Stilnox and Xatral(alfuzosin) 1992 Synthelaboは、Laboratoires Delagrange とLaboratoires Delalandeを買収 1993 Synthelaboは、Laboratoires Pharmaceutiques Goupilを合併 1993 Synthelabo、Stilnox(zolpidem)を米国発売(Ambienの商品名で)、 1994年迄にinsomnia治療薬トップの座に(IMS data). 1994 Sanofiは、米国Sterling Winthrop社(Eastman Kodakの医薬部門)を買収。 1996 Sanofiは、Eloxatine(oxaliplatine)をフランス発売。 1997 Sanofiは、大型製品irbesartan(Aprovel)を欧・米で発売、1988にはclopidogrel (Plavix)発売 1999.5.18 SanofiとSynthelaboが合併→Sanofi-Synthelabo フランスの2大企業グループであるエルフとロレアルそれぞれの医薬品部門が合併し誕生 サノフィは第二位、サンテラボは第三位だった。 ●Annual Report 2002[pdf,219p] Innovating and Acting to improve healthcare through out the world [27p-] Consolidated Financial Statement [120-] - Notes to the consolidated financial statements [127-] - C. ALLIANCES [132-] 提携会社との概要 1)BMSとの共同開発品: 降圧剤irbesartan(Aprovel/Avapro/Karvea) およびthe atherothrombosis treatment clopidogrel (Plavix/Iscover) Sanofi-Synthelaboはまず創製者としてRoyaltyを受け取る 次ぎに両社は、ライセンス先からのRoyaltyを受け取る 欧州・アフリカ・アジアはSanofi-Synthelabo、日本は塩野義、残りがBMS 2)Pharmacia-Searleとの提携契約 催眠剤zolpidem (Ambien)は米国で、合弁会社Lorex Pharmaceuticals (49% by Sanofi-Synthelabo and 51% by Pharmacia-Searle)により販売。 この処理についての詳細説明。 3)Organonとの提携契約 米・欧で2002年に発売されたArixtra。 北米は２社の合弁会社で販売。 欧州と残りの全世界(日本除く)はSanofi-Synthelabo - D.1. Changes in the scope of consolidation [134-] [Significant changes in 2002] 買収は３件。 ・2002.4.16 - 合弁会社Lorex PharmaceuticalsのPharmacia-Searleの持ち分51%を買収100%に ・2002.1.1 - Institut Medical Algerienの100%を買収 註)Lorex Pharmaceuticals 売上 (2001)$905 million, (2000)$709 million - E. LIST OF COMPANIES INCLUDED IN THE CONSOLIDATION FOR THE YEAR ENDED DECEMBER 31, 2002 [155p-](関係会社と持ち株比率) Sanofi-Synthelabo Meiji Pharmaceuticals Co Ltd Japan 51% Sanofi-Synthelabo Taisho Pharmaceuticals Co Ltd Japan 51 Sanofi-Synthelabo Yamanouchi Pharmaceuticals KK Japan 51 Sanofi-Synthelabo KK Japan 100 Lorex Pharmaceuticals Inc.(3) USA 100 Lorex Inc USA 100 Chinoin Hungary 99 ほか
■Aventis - http://www.aventis.com/; 合併後、自動的に→ http://www.sanofi-aventis.com/ ヘ 1999.12 Hoechst[GE]とRhone-Poulenc[FR]が統合し、Aventis S.A.[FR]に。 --- 以下主要子会社 Aventis Pharma[GE,医薬] Aventis Pasteur[FR,ワクチン] ---1999.12 Pasteur Merieux Connaughtから社名変更。see Aventis Pasteur History Aventis Behring L.L.C.[GE,US,血液製剤,Therapeutic Proteins], Aventis CropScience, Aventis Animal Nutrition, Hoechst AG[GE] About Aventis Rhodia S.A.[FR]---1998.1.1 化学系統合 Rhodia Inc.(USA) 2003 20-F - significant subsidiaries of Aventis[主要系列会社] ●主力事業 ★処方薬 従業員数61,000人 [研究開発 5,700人]仏・独・日・米の４か所 [製造部門20,000人] 30か国53工場450製品； [営業部門32,000人] 85か所 ★人体用ワクチン 従業員数 8,000人 [研究開発 1,100人] [製造部門 4,000人] ●関連会社 [Aventis名以外] Merial 50% 動物薬 Merck & Co.との合弁会社 ---- Non-Core Business [2004年末迄に売却予定] Aventis Behring 100% ワクチン 従業員6,200 →2004.5 CSLに売却しZLB Behringに . Rhodia (15.3%) . Wacker (49%) . DyStar (35%) ●Aventis 20-F 2003[pdf,249p] 33p Item 4. Information on the Company 34p Major corporate developments since the formation of Aventis in 1999 1999.12.15 Rhone-Poulenc/Hoechstの合併によりAventisが公式に設立 2001.05.02 工業ガス子会社 Messer Griesheim GmbH を売却 2002.04.03 Aventis Animal Nutrition をCVC Capital Partners に売却 2002.06.03 Aventis CropScienceをBayer AGに売却。(評価額e 7.25 billion) 2003.05.02 Aventisは Rhodia株17.8 million(9.9% of Rhodia総株数)をCrｴedit Lyonnaisに売却 従ってRhodia株の保有は27.5 million株(全体の15.3%) 2003.11.04 Aventisは、スイス化学会社Clariantの11.8%を取得。 2003.12.08 Aventis及びCSL Limited of Australiaは、CSLがAventis Behringを買収する 契約にサイン。 2004.01.26 Sanofi-SynthelaboがAventisを買収するオファー提示。 ★35p Main Business Developments in 2003 [2003.01] ・Taxotere －欧州承認取得。 非小細胞肺癌first-line treatment薬として ・保存剤不要のdiphtheria and tetanus vaccine[Aventis Pasteur] - FDA承認 ・Ketek錠 (telithromycin) - FDA諮問委が承認勧告。 呼吸器感染症。 AventisはFDAから２回目のapprovable letterを受領 [2003.03] ・Lantus - 小児への使用の欧州承認取得。 ・landmark HOPE studyによると、Delix/Tritace (ramipril)がハイリスク循環器疾患 患者で心不全を低減するとの結果。 [2003.04] ・Arava - 日本で関節リウマチ薬として承認 [2003.05] ・Lantus - FDA承認(flexible administration). ・Aventisは、循環器薬cariporideの承認を諦める。 [2003.06] ・Aventis - 速効性インスリン・アナログApidra (insulin glulisine)の米国・欧州で申請 ・Aventisは Zealand Pharmaと契約し、タイプ２型糖尿病薬ZP10 (AVE-0010), a GLP-1 analogue の世界的権利を取得。 ・Arava (leflunomide) - 錠剤について関節リウマチの適応追加でFDA承認 ・Taxotere (docetaxel) - ASCOで乳癌治療の報告 Taxotere regimenが進行性胃癌で生存率を改善 [2003.07] ・ImmunoGen社と新抗癌物質の探索・商品化研究の提携契約 [2003.08] ・Lantus (insulin glargine) - フランスで発売 ・Lovenox (enoxaparin sodium) - 米国でジェネリック品を発売しようとする２社に対し U.S. Patent Number 5,389,618の侵害で提訴 [2003.09] ・Aventisは、Regeneron社との間でVascular Endothelial Growth Factor (VEGF) Trap, an anti-angiogenesis compound の癌および眼科領域の開発で提携 ・Aventisは、U.S. National Institutes of Healthとの間で、Severe Acute Respiratory Syndrome (SARS)用不活化ワクチン開発で提携 ・TAX 311 - a randomized Phase III studyでは、Taxotere (docetaxel)はpaclitaxel, と比較して、metastatic 乳癌患者の生存率を改善 ・Lantus - Aventisはドイツ・フランクフルトに世界で最も近代的なバイオテク・インス リン工場をオープン ・AventisとMerck & Co.は、HIV prime-boost vaccine candidatesの臨床試験開始. ・抗痴呆薬AC-3933 (AVE-3933) - 大日本製薬から日本を除く世界的開発販売権を取得。 [2003.10] ・Ketek and Lantus - 日本で承認。 ・Ketek - FDA approvable letterに基づき、完全な報告を申請 ・Aventisは、Axcan Pharma Incに対して、３種の消化器系医薬品の北米での権利を譲渡 ３品目の売上U.S. $ 42 million in 2002. [2003.11] ・pralnacasan - Aventis and Vertex Pharmaceuticalsは、関節リウマチのP2b臨床試験 を自主的に中止 [2003.12] ・TAX 316 [Taxotereを含むanthracycline-based regimen]の２回目の中間報告で 早期乳癌患者の生存率改善および再発リスクの低減が報告 ・Genasense (oblimersen sodium) - NDA申請完了。 進行性悪性メラノーマで ダカルバジンと併用 ・Aventis Pasteurはインフルエンザワクチンの43 million dosesの出荷確認 ・Aventis はフランスのジェネリック薬会社 RPGを Ranbaxy of Indiaに売却. ・Avalon Pharmaceuticals of Maryland, U.S.と、制癌剤開発で提携 ・quadrivalent conjugate meningococcalワクチンMenactraのFDA-BLAを申請 ・Allegra-D - １日１回の製剤のFDA申請 ・喘息薬Alvesco. - FDA申請 [2004.01] ・Aventis and Crucell - インフルエンザワクチンをCrucell’s proprietary PER.C6 cell line technologyを用いて開発する提携契約. ・Taxotere - 日本で 食道癌(esophageal cancer)の適応で承認. ・Rhodia株の15.3%売却をThe European Commission が認可。 AventisがWacker-Chemieの49%取得をThe European Commission が認可。 [2004.02] ・OptiClick insulin delivery device - 米国と欧州で申請 ・Lantus insulin. - ５年間のORIGIN trialが開始。 心臓疾患リスク低減を検証 ・Aventis and Intercell は細菌ワクチン開発で提携 ★38-43p Products 製品 ★46-49p Pipeline 前臨床30, 臨床早期40, 臨床後期14 新薬申請5, 適応拡大ほか Key Compounds in Late-Stage Clinical Development※元表にデータ追加加工 註)新薬・新成分のみ
※Our early-stage pipeline (phase I/II) includes the following key projects:
Project Disease Status 作用等 備考 Alvesco(ciclesonide)(U.S.) Asthma 申請済 A new-generation inhaled corticosteroid with a competitive safety/efficacy profile. Due to its low systemic exposure, Alvesco offers the potential for use in mild to moderate asthma in both pediatric and adult patients. We are co-developing this compound with Altana Pharma in the U.S. and submitted a new drug application to the U.S. FDA in December 2003. 提携ALTANA Pharma Apidra(insulin glulisine) Type 1 and 2 diabetes 申請済 This rapid-acting insulin analogue for type 1 and type 2 diabetes was submitted for U.S. and EU approval in June. This product is expected to complement our insulin portfolio and particularly our basal insulin Lantus. Genasense(oblimersen sodium) Malignant melanoma 申請済 the first targeted pro-apoptotic agent specific to Bcl-2, a critical protein in the pathway of cell death (apoptosis). Based on data from the phase III pivotal trial in patients with metastatic melanoma who received Genasense plus dacarbazine, Aventis and Genta completed submission of a new drug application (NDA) to the FDA for approval of Genasense for use in the treatment of metastatic melanoma in December 2003. The FDA has granted priority review status to the application. 提携Genta Inc. Ketek Respiratory tract infections 申請済 In response to the second FDA approvable letter of January 2003; Ketek is approved in Europe, Canada, Japan, Latin America. Menactra Meningitis (vaccine) 申請済 the first quadrivalent conjugate vaccine for the prevention of meningococcal meningitis (four serogroups), was submitted for U.S. regulatory approval for use in children age 11 and older as well as adults in December 2003. An EU submission for ages 2-55 is planned for 2004 while submission for use in children ages 2-11 will follow in the U.S. Sculptra Facial lipoatrophy 申請済 an injectable poly-L-lactic acid was acquired in May 2002 from Biotech Industry S.A. of Luxembourg, which developed the product under the name New-Fill. The FDA has accepted the filing of a Premarket Approval Application (PMA) and has also granted an expedited review. Sculptra is a dermal contouring agent that provides lift to help restore lost facial volume in people with lipoatrophy. Lipoatrophy is typically characterized by the loss of fullness, shape, and contour in the face. Adacel (U.S.) Booster vaccine for adults and adolescents Phase III a trivalent vaccine protecting adolescents and adults against pertussis, diphtheria and tetanus. Marketed in Canada and Germany, Adacel is currently in phase III development in the U.S. Exubera Type 1 and 2 diabetes Phase III A novel approach to delivering insulin in a dry powder formulation by inhalation. We are developing Exubera for patients with type 1 and type 2 diabetes in cooperation with Pfizer. A phase III clinical program has been completed and additional studies are underway to strengthen the long-term safety data. Regulatory filings in the U.S. and in Europe are planned for the 2004-2005 time frame. 提携Pfizer Pentacel (U.S.) Pediatric combination vaccine Phase III a vaccine protecting against five diseases (diphtheria, tetanus, polio, whooping cough and Hib meningitis) for the U.S. market. Teriflunomide Multiple sclerosis Phase III an orally active immunomodulator that is being developed for the treatment of multiple sclerosis. 109,881 (new taxoid) Breast cancer Phase III a new taxoid, is a cytotoxic agent that blocks cell replication by interfering with normal cellular function, leading to cell death. It has shown indications of improved efficacy in taxane-resistant patients. 0673 (direct Factor Xa inhibitor) Acute coronary syndrome Phase IIb a direct Factor Xa inhibitor, is a novel agent for the treatment and prevention of arterial and venous thrombosis that very selectively inhibits the plasma coagulation Factor Xa. This new-generation agent offers the potential to inhibit coagulation without the unwanted side effect of bleeding often observed with other antithrombotics. With a fast on- and offset of action, it represents a promising approach for the treatment of acute coronary syndrome. 100,907 Sleep disturbance Phase IIb a selective serotonin (5-HT2a) antagonist with the potential to improve restorative sleep and sleep continuity by reducing the number of night-time awakenings. Pralnacasan (on hold) Rheumatoid arthritis Phase IIb an orally administered ICE (interleukin beta converting enzyme) inhibitor. ICE regulates the production of both interleukin-1 beta (IL-1 beta) and IL-18, key pro-inflammatory cytokines that initiate and sustain the progression of inflammation. Inhibiting ICE may be a useful strategy for curtailing damaging inflammatory processes common to a number of acute and chronic conditions. ※Key regulatory achievements in 2003/4
AVE-8062 Cancer VEGF Trap Cancer ALVAC-CEA vaccine Colorectal tumors ALVAC-gp100 vaccine Melanoma ALVAC-HIV vaccine HIV Dengue vaccine Dengue fever and dengue hemorrhagic fever RSV vaccine Respiratory viral infections Next-generation flu vaccine Influenza AVE-3933 Alzheimer's disease AVE-7688 Hypertension HP-184 Spinal cord injury NV1FGF Peripheral vascular disease Pralnacasan Osteoarthritis and psoriasis Anti-inflammatory compounds Asthma AVE-0010 Diabetes DiaPep277 Diabetes PPAR agonists Diabetes Antiobesics Obesity BARI Metabolism (hypercholesteremia) Guanylate cyclase activators Ang ina SERM Postmenopausal osteoporosis EU-RMS = European Union Reference Member State for Mutual Recognition Procedure NCE = New Chemical Entity LE = Line Extension NSCLC = Non-small-cell lung cancer 2003には, ５新薬を申請、ほかに適応追加など ※Alliances ・In June 2003, we signed a licensing agreement with Zealand Pharma for the development and worldwide commercialization of AVE-0010 (ZP-10), a GLP-1 (glucagon-like peptide-1) receptor agonist of the exendin class that offers the potential to become a novel way of treating type 2 diabetes. AVE-0010 is currently in phase I/II.
Product Indication Achievements Allegra LE Pediatric exclusivity 承認U.S. (January2003) Allegra LE Pediatric tablets 承認UK (EU-RMS)(April 2003) Allegra-D LE Once-daily administration 申請U.S. (Dec. 2003) Alvesco Asthma 申請U.S. (Dec. 2003) ActHib Hib meningitis vaccine Submitted in Japan (March 2003) Apidra NCE Diabetes 申請U.S. and the EU(June 2003) Arava LE Rheumatoid arthritis -improvement of physical function 承認U.S. (May 2003) Arava NCE Rheumatoid arthritis 承認Japan (April 2003) Genasense NCE Malignant melanoma 申請U.S. (Dec. 2003) Ketek NCE Respiratory tract infections 承認Japan (Oct. 2003) Ketek NCE Respiratory tract infections Response to 2nd approvable letter 申請U.S. (Oct. 2003) Lantus NCE Diabetes 承認Japan (Oct 2003) Lantus LE Flexible dosing 承認U.S. (May 2003) Lantus LE Pediatrics 承認EU (March 2003) Lovenox LE 300 mg multidose vial 承認U.S. (Jan. 2003) Menactra Meningococcal meningitis (A, C, Y and W-135) 申請U.S (December 2003) Sculptra Facial lipoatrophy 申請U.S. (December2003) Targocid LE Pediatrics 承認Japan (Jan. 2003) Tavanic LE Prostatitis 申請UK (EU-RMS)(May 2003) Tavanic LE Uncomplicated urinary tract infections 承認UK (EU-RMS) (May 2003) Taxotere LE 1st line NSCLC 承認EU (January 2003) Taxotere LE Esophageal cancer 承認Japan (January 2004) Taxotere LE Endometrial cancer 申請Japan (November2003) Taxotere LE Hormone-refractory prostate cancer 申請U.S. (Jan 2004) and the EU (Feb. 2004)
・In July 2003, Aventis and ImmunoGen signed a collaboration agreement to discover, develop, and commercialize novel antibody-based anti-cancer products.
・In August 2003, we signed a licensing agreement with Dainippon for exclusive worldwide development and marketing rights (excluding Japan) for the antidementia agent AVE-3933. AVE-3933 is a potential cognitive enhancer with a novel mechanism of action under development for the treatment of Alzheimer’s disease.
・In September 2003, Aventis and Regeneron Pharmaceuticals entered into a global agreement (excluding Japan) under which the companies will jointly develop and commercialize Vascular Endothelial Growth Factor (VEGF) Trap, Regeneron’s lead anti-angiogenesis compound. VEGF Trap is currently in phase I clinical trials to test the safety and tolerability of the compound in patients with solid-tumor malignancies and with non-Hodgkin’s lymphoma.
※Major partnerships and in-licensing agreements※Partner Area of collaboration 註) 300以上の前臨床研究でのコラボレーション
Compound Partner Indication Actonel Procter & Gamble Osteoporosis Alvesco Altana Pharma Asthma AMPA kinase inhibitor Mercury Diabetes Anti-inflammatory compounds Inflazyme Asthma Anti-inflammatory compounds Millennium Inflammatory diseases Antibody-based oncology compounds ImmunoGen Cancer AVE-0010 Zealand Pharma Diabetes AVE-3933 Dainippon Alzheimer’s disease AVE-8062 Ajinomoto Cancer Campto Yakult Cancer Cathepsin A inhibitors Celera Inflammatory diseases CpG immunomodulators Coley Asthma and allergic rhinitis Copaxone Teva Pharmaceuticals Multiple sclerosis CRF-1 antagonists Neurogen Anxiety/depression DiaPep277 Peptor Diabetes Dynepo Transkaryotic Therapies Anemia Exubera Pfizer Diabetes Genasense Genta Cancer Nicotinic agonists Targacept Alzheimer’s disease PPAR agonists Genfit Diabetes Pralnacasan Vertex Arthritis (RA and OA) SERM ProSkelia Bone diseases Tavanic Daiichi Bacterial infections VEGF Trap Regeneron Oncology Aventis Pasteur has an established international network of collaborations: ※Vaccine Object Partner
Affymetrix Microarray technology Avalon Cancer gene discovery Celera Genomic information GeneLogic Toxicogenomics ImmunoGen Antibody technology Incyte Pharmaceuticals Genomic information Ingenuity Genomic information management Neogenesis Screening technology ProCorde Cardiovascular functional genomics Universities of Ulm and Freiburg Pharmacogenomics Biotechnology
Flu Delivery systems Crucell Viral High-yield tissue cultures Crucell, Vivalis Dengue Chimeric approach Acambis Dengue Live-attenuated approach Mahidol University HIV Funding for clinical trials NIH, others HIV Adenovirus Merck & Co. Cancer Antigens － research contracts Leiden University, NCI, Karolinska Institute, Therion, Eos ●About Aventis ★Research & Development ★Pipeline ※Drug Innovation & Approval > Pipeline～開発品目 ●Drug Innovation & Approval > Pipeline～開発品目 --- ★Key products under clinical development or in regulatory review
Basic research Privileged access to new findings Institut Pasteur 註) *新規物質のみ *開発段階は、米欧のみ ★Major line extensions
Projects Diseases Status U.S./EU Planned Submissions 備考 Genasense(TM) Cancer PH III 2003[EU][US] Gentaと共同 Arava(R) Rheumatoid arthritis Launched 2001[Jp]済 Ketek(R) Respiratory tract infections Launched 2002[US][Jp済] Lantus(R) Type 1&2 diabetes Launched 2002[Jp] 日2002.4済 1964 Type 1&2 diabetes PH III 2003[EU][US] Cariporide Coronary artery bypass graft PH III 2003[EU][US] Alvesco
(Ciclesonide)Asthma PH III 2003[US] Altana Pharma共同 Menactra(R) ACWY Meningitis(vaccine) PH III 2004[EU][US] Pentacel(R) HIB, pert., dipht., tet., polio PH III 2004[US] 109,881 Cancer PH II 2005[EU][US] Flavopiridol Cancer PH II 2005[EU][US] Exubera(R) Type 1&2 diabetes PH III tbd Pfizer共同
Projects Diseases Planned Submissions Allegra(R) Pediatric exclusivity 2002[US] Perennial allergic rhinitis 2003[US] Allegra-D once daily 2003[US] fast dissolving tablet 2003[US] Asthma 2004[US] Campto(R) Gastric cancer 2003[EU] Colon cancer adjuvant 2004[EU] Ketek(R) Pediatrics 2004[EU][US] Lantus(R) Flexi dosing 2002[EU][US] Pediatrics 2002[EU] Lovenox(R) Deep vein thrombosis prophylaxis 2002[Jp] ST-elevated heart attack 2004[EU][US] Taxotere(R) Gastric cancer 2003[EU][US] Breast cancer adjuvant 2003[EU][US] Prostate cancer 2003[EU][US] Head & neck cancer neoadjuvant 2004[EU][US] ●Aventis 20-F 2003[pdf,249p] ★38-43p Products 製品 次の１５製品が戦略品目 ★外用薬部門 Dermik社が外用処方薬を扱う
[2003]
・2003.9.1 Aventisは外用処方薬を扱うDermik社を含めて、全世界的に外用薬について統合した。
・Dermik社製品は、外用処方薬、マメ・タコ等の足治療製品[podiatry products]、
最近はエステティック・フランチャイズを設立。
Within the prescription dermatology and podiatry business, Dermik focuses on treatments for a wide variety of skin and nail problems, including acne, nail fungus, pre-cancerous lesions, rosacea, psoriasis, dermatitis and eczema.
The leading products in the traditional prescription business currently include: BenzaClin (clindamycin 1%-benzoyl peroxide 5%) Topical Gel, Penlac Nail Lacquer (ciclopirox) Topical Solution (sold as Batrafen in most of Europe), Carac (5 fluorouracil) and Dermatop. The key product within the new aesthetic dermatology franchise is New-Fill, which is currently marketed in 26 countries, including the European Union. An IDE (Investigational Drug Exemption) was filed in the U.S. with the Food and Drug Administration in March 2003.
A PMA (Premarket Approval Application) was filed with the U.S. FDA in December 2003 to market this injectable drug device under the brand name Sculptra in the United States. A regulatory submission in Canada is planned in 2004.
●Merial [Merck & Co.社との50:50合弁会社：動物薬] [2003] ・主な市場 －U.S., France, UK, Brazil, Japan, Canada, Germany, Italy, Australia and Argentina. ・本部：The worldwide headquarters and registered office of Merial Ltd are in Harlow (UK). ・工場１６、研究所１０。 従業員数6,000
●アベンティスフアーマ（株） --- http://www.aventispharma.jp/ アベンティスファーマ㈱[P][B][IT][IO]～サノフィ・アベンティスグループ サノフィ・サンテラボ㈱[IT]～サノフィ・アベンティスグループ - 2004年8月20日、サノフィ･サンテラボがアベンティスの事業を統合し、フランス及び 欧州で第1位、世界第3位製薬企業「サノフィ･アベンティス」が誕生。 日本ではサノフィ･サンテラボ株式会社とアベンティス ファーマ株式会社の両社が、 サノフィ・アベンティスグループとして、2005年1月1日より共同・協調事業を開始。日本法人としては別個に存続。 ★日本での製品売上 （億円；薬価ベース）2001 share アレグラ 164 10.2%(抗ア＋抗ヒ、トップ)/発売00.11 アマリール 52 21%(経口血糖降下剤、SU系トップ) タキソテール 76 27%(制癌剤 ●[日本]国内開発品[2004.2.6現在] 註）元表をベースにデータ補正した。
●上記リストから除外された製品 [2002.5.1リストから更新(2004.3.25)]
開発品 予定されている適応症 新製品/適応追加 開発ステージ 申請予定 XRP9999A静注
(抗ヒト胸腺細胞ウサギ免疫グロブリン)重症・中等症の再生不良性貧血、骨髄移植後の急性移植片対宿主病 新製品 申請中 2002済 タキソテール
XRP6976M(ドセタキセル）静注食道癌 適応追加 承認
04.1.192002済 乳癌、非小細胞肺癌、胃癌、頭頸部癌、卵巣癌で発売 タキソテール
XRP6976T(ドセタキセル）静注子宮体癌 適応追加 申請中 2003済 乳癌、非小細胞肺癌、胃癌、頭頸部癌、卵巣癌で発売 タキソテール
XRP6976J(ドセタキセル）静注前立腺癌 適応追加 Ph. IIa準備中 2005 乳癌、非小細胞肺癌、胃癌、頭頸部癌、卵巣癌で発売 アレグラ
M016455O(塩酸フェキソフェナジン)錠剤アレルギー性鼻炎･じんましん・皮膚疾患に伴う皮膚そう痒症（小児用） 錠剤 用法用量追加
・剤型追加申請中 2004済 アレルギー性鼻炎、蕁麻疹、皮膚疾患に伴うそう痒（成人用量）で発売 XRP4563K皮下注
(エノキサパリン)股関節又は膝関節置換術施行後における深部静脈血栓の防止 新製品 申請準備中 2004 ケテック
HMR3647G（テリスロマイシン）錠剤皮膚軟部組織感染症、子宮内感染 適応追加 Ph. III 2004 ケテック
HMR3647B（テリスロマイシン）細粒呼吸器感染症、皮膚軟部組織感染症、中耳炎、副鼻腔炎（小児用） 適応追加 Ph. III 2006 遺伝子組換えヒトインスリンアナログ インスリン療法が適応となる糖尿病 新製品 Ph. III 2006 Apidra(insulin glulisine)(米欧2003.6申請済み)と推定
開発品 予定されている適応症 新製品/適応追加 開発ステージ 申請予定 アラバ錠10mg,20mg,100mg
(レフルノミド)関節リウマチ 新製品 発売
03.9.122001 承認03.4.16 タゴシッド MRSA感染症 (小児用）敗血症、せつ・せつ腫症、癰、皮化膿症・膿皮症、手術創等の表在性二次感染、慢性気管支炎、肺炎、膿胸 用法用量追加 承認
2003.12001 成人適応すべてに小児用 ケテック錠300mg
(テリスロマイシン)呼吸器感染症、副鼻腔炎、歯科口腔外科領域感染症 新製品 発売
03.12.152002 03.10.16承認
販売：三共、藤沢ランタス
(インスリングラルギン)インスリン療法が適応となる糖尿病 新製品 発売
03.12.122002 アレグラ アトピー性皮膚炎、湿疹・皮膚炎、皮膚そう痒症（1日2回投与） 適応追加 承認
02.4.152001 現在適応は、アレルギー性鼻炎、蕁麻疹、皮膚疾患（湿疹・皮膚炎、皮膚そう痒症、アトピー性皮膚炎）に伴うそう痒 アレグラ アレルギー性鼻炎(１日１回投与） 用法追加 Ph. III 2002 中止？ タキソテール ウィークリースケジュール(非小細胞肺癌) 適応追加 Ph. IIa 2003 中止？ タキソテール ウィークリースケジュール(乳癌） 適応追加 Ph. IIa 2003 中止？
●Sanofi Pasteur SA[FR,ワクチン] - http://www.sanofipasteur.com/; 本社フランス ---2005.1 Aventis Pasteur[FR]からSanofi-Pasteurに社名変更 同時にMerckとの合弁Aventis Pasteur MSDもSanofi Pasteur MSDに変更。 ---1999.12 Pasteur Merieux ConnaughtからAventis Pasteurに社名変更。 売上高Euro 2.114 billion(2003) 、従業員8,500人以上。 仏・米・加に研究所(from Facts & Figures) ---1989. Pasteur Merieux serums & vaccins[仏]当時Rhone-Poulenc子会社は Connaught Laboratories Limited[加]を買収 ●Press Release - http://www.sanofipasteur.com/sanofi-pasteur/front/templates/vaccinations-travel-health-vaccine-aventis-pasteur.jsp?codeRubrique=13&lang=EN ●Our Vaccines List of Vaccines Against 20 diseases
●Sanofi Pasteur Inc. -US[US,ワクチン] - http://www.sanofipasteur.us/sanofi-pasteur-us/front/pages/vaccination-immunology-vaccines-aventis-pasteur.jsp ●Our Vaccines ★List of Vaccines ★Other Products ★Against 20 Diseases ●Media Center - Community Relations - Corporate News - Product News
●サノフィパスツール - http://www.sanofipasteur.jp/ 当社の製品にはジフテリア、黄熱、インフルエンザ、インフルエンザ桿菌タイプB (Hib)、 Ａ・Ｂ型肝炎、脳炎、百日咳、ポリオ、肺炎、狂犬病、髄膜炎菌性髄膜炎、麻疹、ムンプ ス (お多福風)、風疹、破傷風、結核、腸チフス等のワクチン及び混合ワクチンが揃っています。 各種参考資料がある
■Santhera Pharmaceuticals Ltd.[瑞]
- http://www.santhera.com/ ; Hammerstrasse 47, CH-4410 Liestal, Switzerland 篤な神経筋疾患を対象とした低分子化合物治療薬の創薬・開発・販売に特化しており、 この分野における希少疾患におけるアンメット・ニーズを満たすことを目的としています。
●Santhera Pharmaceuticals Ltd.[瑞] ●Media Center - News releases ●Pipeline ★SNT-MC17 (INN: idebenone) for the treatment of Friedreich's Ataxia (FRDA) - EMEA申請2007.8(フリードライヒ失調症治療薬) , Duchenne Muscular Dystrophy (DMD) -P2 and Leber's Hereditary Optic Neuropathy (LHON). -P2(Leber病) In August 2007, the EMEA accepted Santhera's file for European marketing approval of SNT-MC17 in FRDA. The Company has been granted orphan drug designation in the US and Europe for SNT-MC17 in FRDA, DMD as well as LHON. ★JP-1730 (INN: fipamezole) for the treatment of Dyskinesia (involuntary movements) in Parkinson's Disease patients (DPD). - P2 From Juvantia Pharma (2006) A fast track designation status has been granted by the FDA for JP-1730 in DPD. ★SNT-317 (INN: omigapil) - 先天性筋ジストロフィー in Congenital Muscular Dystrophy (CMD) and other neuromuscular diseases -P2 from Novartis (July 2007) ●Investors ●Reports Santhera Profile 2006 Financial Report 2006 ●News Releases
■Savient Pharmaceuticals, Inc.
- http://www.savientpharma.com/index.asp ; 本社East Brunswick, New Jersey 1980年 Bio-Technology General Corp.として設立(バイオテク事業) 2001.3 Myelos Corporation(非公開の神経系バイオ開発企業) を買収。 2002.9 英国Rosemont Pharmaceuticals Limited(英、EUで100種以上の経口液剤を販売)を買収。 (子会社Acacia Biopharma Limited経由) 2003.6 Savient Pharmaceuticals, Inc.に社名変更 2005.7 イスラエル子会社Bio-Technology General (Israel) Ltd. (BTG-Israel). をFerring B.V. and Ferring International Centre S.Aに売却。 2006.1 注射用Delatestryl(testosterone;適応male hypogonadism)をIndevus Pharmaceuticals, Incに売却。 対価は$5 millionと３年間の売上収入からの一定割 2006.8 英国子会社Rosemont Pharmaceuticals, Ltd (英、EUで100種以上の経口液剤を販売)をIngleby (1705) Limited (Close Brothers Private Equity) に売却●会社決算
($ 000) 2010 2009 2008 2007 2006 2005 2004 2003 2002 備考 製品売上 4,028 2,956 3,028 13,825 47,351 48,043 59,401 68,909 60,226 他の収入 0 4 153 199 163 1,452 2,952 5,048 4,399 (収入 計) 4,028 2,960 3,181 14,024 47,514 49,495 62,353 73,957 64,625 営業利益 (55,984) (81,162) (89,011) (69,174) (17,005) (14,480) (19,616) (796) (2,655) 継続事業利益 (73,109) (90,853) (83,241) (49,155) (1,464) (469) (33,413) (538) (2,733) 中止事業からの収入 - - (928) 487 61,789 6,437 5,898 12,992 11,412 当期純利益 (73,109) (90,853) (84,169) (48,668) 60,325 5,968 (27,515) 12,454 8,679 研究開発費 32,358 51,726 55,488 50,870 21,412 16,980 19,249 従業員数[連結] 129 43 73 75 67 ●製品売上 Oxandrin 1,324[32.9%] (366)[-12.4%] (357)[-11.8%] 8,425[60.9%] 46,965[99.2%] 44,405[92.4%] 53,520[90.1%] [Oxandrolone]体重回復 Oxandrolone 2,686[66.7%] 3,322[112.4%] 3,385[111.8%] 5,400[39.1%] 469[1.0%] - - [Oxandrolone]2006.12.29発売、Watson経由で販売 KRYSTEXXA 18[0.4%] - - - - - - - - [pegloticase]通風 Delatestryl - - - - (83)[-0.2%] 3,638[7.6%] 5,881[9.9%] [Testosterone Enanthate]hypogonadism;2006.1.9 Indevusに譲渡
●Oxandrin(R)(Oxandrolone) 術後等体重回復補助剤 ・1995.12 発売。 HIV/AIDSによる体重減少に苦しむ患者に多く使われて。 [適応症] as adjunctive therapy to promote weight gain after weight loss following extensive surgery, chronic infections, or severe trauma, and in some patients who without definite pathophysiologic reasons fail to gain or to maintain normal weight, to offset the protein catabolism associated with prolonged administration of corticosteroids, and for the relief of bone pain frequently accompanying osteoporosis. 【2010】
Oxandrin is an oral synthetic derivative of testosterone used to promote weight gain following involuntary weight loss related to disease or medical condition. We sell Oxandrin in both 2.5 mg and 10 mg tablets. We first introduced Oxandrin in the 2.5 mg strength in December 1995 and followed with the 10 mg tablet in October 2002. We introduced the 10 mg strength to reduce the number of tablets required to be taken by patients taking 20 mg a day, which is a common dosage. For the years ended December 31, 2010 and 2009, approximately 41% and 46%, respectively, of all Oxandrin prescriptions were being filled with the 10 mg tablet. Since our 1995 launch of Oxandrin, our Oxandrin sales have been primarily for the treatment of patients suffering from HIV/AIDS-related weight loss.Our financial results have been partially dependent on sales of Oxandrin since its launch in December 1995. Generic competition for Oxandrin began in December 2006. The introduction of generic products has caused a significant decrease in our Oxandrin revenues, which has had an adverse affect on our financial results and cash flow. In response to the generic competition, we scaled back some of our business activities and eliminated our sales force related to the product. As a result, Oxandrin has become a less significant product for our future operating results.
In response to the December 2006 introduction of generic competition for Oxandrin, we, through our distribution partner Watson Pharma, Inc., or Watson, began distributing an authorized generic version of oxandrolone tablets, USP C-III, an Oxandrin brand equivalent product. The authorized generic version of oxandrolone tablets has met all quality control standards of the Oxandrin brand and contains the same active and inactive pharmaceutical ingredients. We have a supply and distribution agreement in effect with Watson which provides for us to receive a significant portion of the gross margin earned by Watson on sales of oxandrolone.
Sales of Oxandrin and our authorized generic version of oxandrolone accounted for 99.6%, 100% and 95% of our 2010, 2009 and 2008 revenues, respectively.
Sales and Distribution
We sell Oxandrin in the United States through our third-party logistics provider ICS, mainly to three drug wholesaler customers: Cardinal Health, AmerisourceBergen Corp. and McKesson Corp. Our sales to these three wholesalers as a percentage of our total gross sales of Oxandrin relating to continuing operations were 80%, 74%
and 83% for the years ended December 31, 2010, 2009 and 2008, respectively. In December 2006, we began selling our authorized generic version of oxandrolone to Watson for distribution in the United States.
Sales of oxandrolone through Watson accounted for approximately 62%, 59% and 44% of our 2010, 2009 and 2008 total gross sales respectively.
Gedeon Richter Ltd.
In February 1999, we entered into a supply agreement for oxandrolone bulk API with Gedeon Richter Ltd., or GRL, pursuant to which GRL served as our exclusive manufacturer and distributor of oxandrolone bulk API in the United States. Under the agreement, we were required to make specified minimum purchases. In April 2007, in response to the introduction of generic forms of oxandrolone tablets by competitors, we and GRL mutually agreed to amend the supply agreement. Under the terms of the amended agreement, we and GRL eliminated our future purchase commitment obligations and the provisions for supply exclusivity, and we purchased GRL’s remaining inventory of oxandrolone bulk API. The initial term of the amended agreement expired in December 2010 and automatically renewed for a successive one-year period. These renewal periods will continue until such time as we or GRL terminate the agreement with advance notice of one year.
DSM Pharmaceuticals, Inc.
In December 2002, we entered into a supply agreement with DSM Pharmaceuticals, Inc., or DSM, for the manufacture of 2.5 mg and 10 mg Oxandrin and our authorized generic oxandrolone tablets. Under the agreement, which was amended in April 2007, we are obligated to supply DSM with sufficient quantities of oxandrolone bulk API, which we acquire from GRL, for DSM’s production of the Oxandrin and authorized generic oxandrolone tablets. We are obligated to submit a rolling forecast to DSM on a monthly basis setting forth the total quantity of Oxandrin and authorized generic oxandrolone tablets that we expect to require in the following 18 months. The first six months of each forecast represent a rolling firm irrevocable order. Our agreement with DSM expired in December 2010.
At this time, we do not intend to seek an alternative manufacturer for Oxandrin and authorized generic oxandrolone tablets. DSM has manufactured sufficient quantities of Oxandrin and authorized generic oxandrolone during 2010 prior to the termination of the supply agreement to adequately supply the products to our customers for at least the next two years.
Watson Pharma, Inc.
In June 2006, we entered into a supply and distribution agreement with Watson, pursuant to which Watson serves as the exclusive U.S. distributor of our authorized generic version of oxandrolone, an Oxandrin-brand equivalent product that we supply to Watson. Under the agreement, we began providing oxandrolone to Watson for U.S. distribution in December 2006. We receive a significant portion of the gross margin earned by Watson on the sale of the product.
The agreement has an initial term ending in June 2016, and either we or Watson may terminate the agreement upon one-year’s advance notice. Additionally, either we or Watson may terminate the agreement at any time in the event of insolvency or uncured material breach by the other party.
【Competition】
In the United States, Oxandrin and our authorized generic version of oxandrolone compete against several other anabolic agents and appetite stimulants. Each of these competing products has different strategies and resources allocated to its promotion as compared to Oxandrin and oxandrolone. In addition, Oxandrin faces competition from oxandrolone generics, including our authorized generic version of oxandrolone. Generic competition for Oxandrin began in December 2006. Our generic competitors are Sandoz Pharmaceuticals, Upsher-Smith Laboratories, Par Pharmaceuticals and Roxane Laboratories.
[2006] ・generic品出現に伴い、2006.12 当社もgeneric品(Watson Pharmaceuticals, Incとの契約)を発売。 ●KRYSTEXXA®(pegloticase)[旧Puricase] P3 痛風 a drug targeting the control of elevated uric acid levels in the blood, or hyperuricemia, in patients with symptomatic gout in whom conventional treatment is contraindicated or has been shown to be ineffective. FDAオーファン指定 Mountain View Pharmaceuticals, Inc. and Duke Universityが特許保持、ライセンス独占契約を締結している。 【2010】
OverviewWe are a specialty biopharmaceutical company focused on commercializing KRYSTEXXA ® (pegloticase) in the United States and completing the development and seeking regulatory approval outside of the United States for KRYSTEXXA, particularly in the European Union. KRYSTEXXA was approved for marketing by the U.S. Food and Drug Administration, or FDA, on September 14, 2010 and became commercially available in the United States by prescription on December 1, 2010, when we commenced sales and shipments to our network of specialty and wholesale distributors.
The active pharmaceutical ingredient, or API, in KRYSTEXXA is a PEGylated enzyme that converts uric acid to allantoin. KRYSTEXXA is indicated for the treatment of chronic gout in adult patients refractory to conventional therapy. Chronic gout that is refractory to conventional therapy occurs in patients who have failed to normalize serum uric acid and whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors, at the maximum medically appropriate dose or for whom these drugs are contraindicated. KRYSTEXXA is not recommended for the treatment of an elevation of blood concentration of uric acid that is not accompanied by signs or symptoms of gout, a condition referred to as asymptomatic hyperuricemia.
Gout develops when urate accumulates in the tissues and joints as a result of elevated blood concentration of uric acid. Gout is usually associated with bouts of severe joint pain and disability, or gout flares, and tissue deposits of urate, or gout tophi, which may occur in concentrated forms. Patients with severe gout have an associated increased risk of kidney failure and increased risk of cardiovascular disease. Uricase, an enzyme not naturally expressed in humans but present in other mammals, eliminates uric acid from the body by converting uric acid to allantoin, which is easily excreted by the kidney. We believe that treatment with KRYSTEXXA controls hyperuricemia and provides clinical benefits by eliminating uric acid in the blood and tissue deposits of urate.
Based on data from the National Health and Nutrition Examination Survey, a biennial survey conducted by the U.S. Centers for Disease Control and Prevention, we believe that there are approximately five million to eight million adults in the United States who suffer from gout. KRYSTEXXA is indicated only for those adult patients who suffer from chronic gout and who are refractory to conventional therapy. We currently estimate the total available market for KRYSTEXXA to be approximately 170,000 patients in the United States, although the size of the market is difficult to predict with accuracy. In addition, the total available market opportunity for KRYSTEXXA will ultimately depend on, among other things, our marketing and sales efforts, reimbursement and market acceptance by physicians, infusion site personnel, healthcare payers and others in the medical community.
The FDA granted KRYSTEXXA an Orphan Drug designation in 2001, which we expect will provide the drug with orphan drug marketing exclusivity in the United States until September 2017, seven years from the date of its approval. The composition, manufacture and methods of use and administration of KRYSTEXXA are also the subject of a broad portfolio of patents and patent applications, which we expect, assuming issuance of currently pending patent applications, will provide patent protection through 2026.
We have substantially completed our preparations for the full promotional launch of KRYSTEXXA in the United States with our sales force commencing field promotion to physicians on February 28, 2011. During the first quarter of 2011, we hired our initially planned 60 person sales force, with biologic drug experience, six regional business directors, six regional medical scientists and six managed care executives. We are also planning to hire an additional 12 field reimbursement specialists and may increase the number of sales force professionals in the future, if deemed necessary. This sales force will allow us to target the rheumatologists and nephrologists with access to infusion centers that treat adult patients suffering from chronic gout refractory to conventional therapy. We have built an inventory of finished KRYSTEXXA product as of December 31, 2010 that is packaged and labeled for distribution and additional supplies of bulk product that are scheduled to be packaged and labeled as part of our ongoing FDA-approved commercial manufacturing process. We believe this inventory will be sufficient for us to meet internal estimates of market demand through the first quarter of 2012. To date, several large private managed care organizations have added KRYSTEXXA as a covered medical benefit and other managed care organizations are actively evaluating medical benefits coverage. In December 2010, we filed for a temporary “C” code and a permanent “J” code application with the U.S. Centers for Medicare & Medicaid Services for reimbursement of the cost of treatment with KRYSTEXXA. We are also currently in contract negotiations with the U.S. Department of Veterans Affairs, or the VA, for KRYSTEXXA to be covered for reimbursement for VA member patients. We expect to have a contract in place with the VA to cover and reimburse KRYSTEXXA by the end of the first quarter of 2011, or shortly thereafter.
In support of our efforts to obtain regulatory approval for KRYSTEXXA outside of the United States, we are preparing to submit a Marketing Authorization Application, or MAA, for centralized review in the European Union. In December 2010, the Pediatric Committee of the European Medicines Agency approved our pediatric investigation plan for the treatment and prevention of hyperuricemia, which is a condition to filing for marketing approval in the European Union. We currently expect to submit our MAA for KRYSTEXXA by the end of the first quarter of 2011 or soon thereafter.
We also sell and distribute branded and generic versions of oxandrolone, a drug used to promote weight gain following involuntary weight loss. We launched our authorized generic version of oxandrolone in December 2006 in response to the approval and launch of generic competition to Oxandrin ® , our branded version of oxandrolone. The introduction of oxandrolone generics has led to significant decreases in demand for Oxandrin and our authorized generic version of oxandrolone. We believe that revenues from Oxandrin and our authorized generic version of oxandrolone will remain flat or continue to decrease in future periods.
We currently operate within one “Specialty Pharmaceutical” segment, which includes sales of KRYSTEXXA, Oxandrin and oxandrolone and the research and development activities of KRYSTEXXA. Total revenues from continuing operations were $4.0 million in 2010, an increase of $1.0 million, or 36%, from $3.0 million in 2009.
Our Board of Directors appointed John H. Johnson as our Chief Executive Officer and elected Mr. Johnson to serve as a member of our Board of Directors, both effective January 31, 2011. Prior to joining us, Mr. Johnson served as a Senior Vice President of Eli Lilly and Company and President of Lilly Oncology, Eli Lilly’s oncology business unit. From August 2007 to November 2009, Mr. Johnson was Chief Executive Officer of ImClone Systems, or ImClone, and served on ImClone’s Board of Directors until ImClone was acquired by Eli Lilly and Company in November 2008. Prior to joining ImClone, Mr. Johnson served as Company Group Chairman of Johnson & Johnson’s Worldwide Biopharmaceuticals unit, responsible for commercial businesses including Centocor, Inc., Ortho Biotech Products, L.P. and the Worldwide Strategic Marketing group. Mr. Johnson also served as President of Ortho Biotech Products, L.P. We expect that Paul Hamelin, our President since November 2008 and previously our most senior executive officer, will continue in his current role with us through a transition period and then leave to pursue other interests.
In February 2011, Louis Ferrari was appointed as our Senior Vice President, North America Commercial. Mr. Ferrari previously served as Vice President of Oncology and Nephrology, Sales and Marketing at Centocor Ortho Biotech. Prior to that he served as Vice President of Clinical Affairs and Executive Director of Clinical Affairs at Centocor Ortho Biotech. Mr. Ferrari has also held positions at Johnson and Johnson, Oxford GlycoSciences, Ortho-McNeil Pharmaceutical and Lilly. Mr. Ferrari earned his Bachelor of Science in Pharmacy from the Brooklyn College of Pharmacy and a Masters of Business Administration from Adelphi University.
KRYSTEXXA ® (pegloticase)
The API in KRYSTEXXA is a PEGylated enzyme that converts uric acid into allantoin. KRYSTEXXA is indicated for the treatment of chronic gout in adult patients refractory to conventional therapy. We produce the uric acid degrading enzyme uricase, using a third-party manufacturer, through a recombinant process in which genetically engineered bacteria produce uricase. We then produce the API, pegloticase, by PEGylating the purified uricase in order to decrease the rate at which the human body would otherwise clear the uricase. PEGylation refers to a process in which a polyethylene glycol polymer is attached to a molecule. With KRYSTEXXA, we PEGylate uricase by attaching methoxypolyethylene glycol, or mPEG, to it.
KRYSTEXXA received “orphan drug” designation from the FDA in 2001. Orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process; however, it does make the product eligible for orphan drug exclusivity and some financial benefits including specific tax credits in the United States. Generally, if a product with an orphan drug designation subsequently receives the first marketing approval for the use for which it has such designation, the product is entitled to orphan drug exclusivity. In such a case, later applications by other companies to market the same drug for the same use may not be approved in the United States for a period of seven years, except in limited circumstances, such as if a competitive product is shown to be clinically superior to the original product. Orphan drug designation of KRYSTEXXA does not prevent competitors from introducing different competing drugs for the same orphan indication that is covered by KRYSTEXXA’s orphan designation or the same drug for a different indication.
Phase 1 Trials
In 2001, we conducted the first of two Phase 1 clinical trials at the Duke University Medical Center, using subcutaneous delivery of KRYSTEXXA. The results demonstrated that over the three-week period of observation, uric acid levels decreased as the dosage of KRYSTEXXA increased. Two of 13 individuals participating in the study experienced allergic-type reactions. Therefore, we terminated the trial and abandoned the subcutaneous delivery approach.
We completed a second Phase 1 clinical trial in 2003 in which KRYSTEXXA was administered intravenously. The results of this trial demonstrated that plasma uric acid levels decreased as blood level of KRYSTEXXA enzyme activity increased. This trial allowed us to identify a minimum effective dosage of KRYSTEXXA and the dosage at which plasma uric acid levels were no longer improved by increasing the dosage of KRYSTEXXA, which is referred to as a dose-response plateau. In this second Phase 1 intravenous trial, no clinical allergic responses were observed, no infusion reactions were reported, and no adverse reactions at the site of intravenous infusion were noted.
Phase 2 Trials
In 2004, we conducted an open label, randomized, three-month Phase 2 safety and efficacy clinical trial of KRYSTEXXA to determine an appropriate dose and dose regimen and to support further testing in pivotal Phase 3 trials. There were 41 participants in this trial. The results of the study confirmed and extended the single dose data obtained in Phase 1, again showing a minimum effective dose and a dose-response plateau in terms of plasma uric acid normalization. These results supported our view as to KRYSTEXXA’s potential efficacy in reducing circulating uric acid. The most common adverse events observed in the Phase 2 trial were gout flares. In addition, 44% of patients experienced one or more adverse events that we determined may have been related to the drug infusion. No other important safety concerns arose from the Phase 2 data set.
Phase 3 Trials
Based on the results of our end-of-Phase 2 meeting with the FDA and post-meeting interactions, in December 2005, we submitted a protocol to the FDA under a Special Protocol Assessment, or SPA, for a Phase 3 clinical trial for KRYSTEXXA. In May 2006, we received written notification from the FDA concurring that the Phase 3 protocols that we had specified were adequate to address the objectives of our Phase 3 clinical program. In June 2006, we began patient dosing in our two replicate Phase 3 clinical trials of KRYSTEXXA for the treatment of chronic gout in patients refractory to conventional therapy, and patient recruitment was completed in March 2007.
These North American trials were multicenter, randomized, double-blind, placebo-controlled trials comparing KRYSTEXXA 8 mg intravenously every two weeks or every four weeks to placebo (every two weeks) in patients with chronic gout refractory to conventional therapy. Patients were randomized to the two treatment groups and placebo in a 2:2:1 ratio, meaning that for every one patient in the placebo group, there were two patients in the every two weeks dosing group and two patients in the every four weeks dosing group. Patients were stratified by presence or absence of tophi. In order to maintain the blinded nature of the studies, patients in the every four weeks dosing group received a placebo dose two weeks after each dose.
The duration of each study was 26 weeks, including two weeks for screening and 24 weeks of treatment. The trials enrolled male and female patients at least 18 years old, hyperuricemic (with a serum uric acid level of at least 8 mg/dL) with symptomatic gout (at least three gout flares experienced in the 18 months prior to entry, or at least one gout tophus, or gouty arthritis) and for whom conventional urate-lowering therapy was contraindicated or had been ineffective. After completion of each study, patients were offered the option of continuing active treatment for up to an additional 24 months in an open label extension, or OLE, study.
In the first clinical trial of the two replicate studies conducted in the United States and Canada, there were 104 patients dosed (comprising the intent-to-treat population): 43 in the KRYSTEXXA every two weeks dose group, 41 in the KRYSTEXXA every four weeks dose group, and 20 in the placebo group. In the second clinical trial of the two replicate studies conducted in the United States and Mexico, there were 108 patients dosed (comprising the intent-to-treat population): 42 in the KRYSTEXXA every two weeks dose group, 43 in the KRYSTEXXA every four weeks dose group, and 23 in the placebo group.
We completed the treatment portion of our Phase 3 clinical trials of KRYSTEXXA in October 2007. The results from the Phase 3 trials showed that KRYSTEXXA 8 mg administered by a two-hour intravenous infusion every two weeks met the primary efficacy endpoint (statistically significant as compared to placebo) in the intent-to-treat population (received at least one dose of study drug) analyses in each of the two replicate, six-month Phase 3 clinical trials. The every four weeks dose group also met the primary efficacy endpoint (statistically significant as compared to placebo). The primary efficacy endpoint specified in the protocol was the normalization of plasma uric acid for more than 80% of the time during months three and six of the clinical trials.
In the first clinical trial of the two replicate studies, the proportion of patients who met the primary endpoint for the every two weeks dose group was 47% (p is less than 0.001 as compared to placebo), and the proportion of patients who met the primary endpoint for the every four weeks dose group was 20% (p is equal to 0.044 as compared to placebo). In the second clinical trial of the two replicate studies, the proportion of patients who met the primary endpoint for the every two weeks dose group was 38% (p is less than 0.001 as compared to placebo), and the proportion of patients who met the primary endpoint for the every four weeks dose group was 49% (p is less than 0.001 as compared to placebo). Pooled across both studies, the proportion of patients who met the primary endpoint for the every two weeks dose group was 42% (p is less than 0.001 as compared to placebo), and the proportion of patients who met the primary endpoint for the every four weeks dose group was 35% (p is less than 0.001 as compared to placebo). The proportion of patients who met the primary endpoint for the placebo group was zero in both trials.
We assessed the following secondary endpoints using pre-specified pooled analyses (both studies combined) of each KRYSTEXXA treatment group as compared to placebo:
・the proportion of patients with a tophus complete response, which is the elimination of a tophus without worsening of any other tophus or the appearance of a new tophus,
・reduction in number of tender joints,
・reduction in number of swollen joints,
・improvement in the clinician’s global assessment of disease activity,
・improvement in patient-reported outcomes as measured by patient’s assessment of pain, patient’s global assessment of disease activity and patient’s assessment of disability using the Health Assessment Questionnaire, improvement in patient-reported outcomes as measured by patient’s assessment of health-related quality of life using the Medical Outcomes Survey Short Form 36, or SF-36, and
・reduction in the incidence and frequency of gout flares.The following endpoints for the KRYSTEXXA every two weeks dose groups were statistically significant as compared to placebo:
・elimination of gout tophi in 40% of patients who received KRYSTEXXA as compared to 7% who received placebo. This endpoint also achieved statistical significance in each of the two studies individually,
・reduction in the number of tender joints and improvement in the clinician’s global assessment of disease activity,
・improvement in the patient-reported outcomes as measured by patient’s global assessment of disease activity and patient’s assessment of disability using the Health Assessment Questionnaire,
・improvement in patient-reported outcomes as measured by patient’s assessment of overall health-related quality of life and pain as measured by the SF-36 physical component summary and bodily pain domain, and
・reduction in the incidence and frequency of gout flares. As expected and is common with initiation of any urate lowering therapy, we observed an increase in the incidence and frequency of gout flares in months one through three of the trial as compared to placebo, followed by a reduction in the incidence and frequency of gout flares in months four through six of the trial as compared to placebo.The following endpoints in the KRYSTEXXA every two weeks dose groups were not statistically significant as compared to placebo:
・reduction in swollen joints, and
・the mental component summary and the other dimensions (other than bodily pain) as measured by the SF-36 physical component summary.The primary endpoints were also met in the every four weeks dose group, though fewer of the secondary endpoints were met than in the every two weeks dose group. As discussed further below, the every two weeks dose regimen, we believed, presented a much clearer path toward FDA approval, so we focused exclusively on this dosing regimen.
The most common adverse events in the trials were gout flares, which occurred in 76% of patients in the every two weeks dose group, 83% of patients in the every four weeks dose group, and 81% of patients in the placebo group. An initial increase in gout flares (followed by a later decrease in gout flares) is an expected side effect of urate-lowering therapies. Standard gout flare medicines, such as colchicine or non-steroidal anti-inflammatory drugs, were administered to help prevent gout flares. The second most common adverse events in the trials were infusion reactions, which occurred in 26% of patients in the every two weeks dose group, 40% of patients in the every four weeks dose group and 5% in the placebo group. Most infusion reactions were managed by slowing the infusion or by stopping and restarting the infusion at a slower rate. Sometimes the physician also administered intravenous fluid or additional antihistamine or anti-inflammatory drugs to treat the infusion reaction. As a prophylactic measure, all patients received a standardized regimen of glucocorticoids, antihistamines and acetaminophen to help mitigate the occurrence and severity of infusion reactions. Eleven of 169 KRYSTEXXA-treated patients in the Phase 3 clinical trials, or 6.5%, had an infusion reaction reported as a severe adverse event, and 12% withdrew because of infusion reactions.
In late January 2009, under the auspices of the BLA Oversight Committee of our Board of Directors, we completed the first of three formal blinded and unblinded post-hoc adjudication of all cardiovascular events included in reports of serious adverse events and serious infusion reactions from the Phase 3 trial. Our evaluation was predicated on the Anti-Platelet Trialist Collaborative, or APTC, assessment criteria, which is a standardized approach that the FDA has widely accepted as a method of evaluating cardiovascular risk. APTC cardiovascular events include deaths, non-fatal myocardial infarction and non-fatal stroke. As a result of the review, we concluded that there were three APTC cardiovascular events in the KRYSTEXXA treatment arms of the Phase 3 trials (not including the OLE study) and none in the comparator placebo treatment arm. We also found that there were 10 non-APTC cardiovascular events in the treatment arms and no non-APTC cardiovascular events in the comparator placebo treatment arm. In addition, we evaluated cardiovascular events in the Phase 2 trial and the OLE study. However, because there was no placebo arm in the Phase 2 trial or the OLE study, there were no comparative results between the treatment group and the placebo group.
In late January 2009, we completed an additional analysis by reviewing all cause mortality in the Phase 3 trials and the OLE study. In that review, we noted that in the Phase 3 trials, there was a 2:2:1 randomization used, meaning that four times as many patients were receiving KRYSTEXXA treatment than placebo. We determined that five deaths were in the KRYSTEXXA treatment arm of the combined Phase 3 trials and the OLE study, and three deaths were in the placebo comparator arm of the Phase 3 trials.
On June 16, 2009, the FDA convened the Arthritis Advisory Committee, or AAC, in order to seek advice as part of the FDA’s regulatory decision-making process of the safety and efficacy data for KRYSTEXXA. The AAC reviewed separate data presentations by us and the FDA and discussed specific questions asked by the FDA. The AAC recommended by a vote of 14 to 1 that KRYSTEXXA be granted marketing approval by the FDA for the treatment of chronic gout in patients refractory to conventional therapy.
Open Label Extension Study
The purpose of the OLE Study was to better understand the long-term safety of KRYSTEXXA in all patients who have completed the Phase 3 trials including those patients that received placebo during the Phase 3 trials. Patients did not know their Phase 3 group assignment or uric acid values and were permitted to choose to go on or continue on KRYSTEXXA every two weeks or every four weeks or enter an observation group. One hundred fifty-seven patients completed one of the replicate double-blind pivotal Phase 3 clinical trials. One hundred fifty-one patients decided to enroll in the OLE study, 82 of whom decided to initially receive pegloticase 8 mg treatment every two weeks, 67 of whom decided to initially receive pegloticase 8 mg treatment every four weeks and two of whom decided to be observed without further infusions.
In the OLE study, the frequency of safety data collection was identical to the measures used in the Phase 3 trials while efficacy assessments were less frequent. Although there was no concurrent placebo comparator group, the interim efficacy and safety data of KRYSTEXXA in the OLE study appeared to be consistent with the randomized controlled Phase 3 clinical trials.
In early July 2009, we completed the patient dosing phase of the OLE study, and in January 2010, we completed a protocol-specified six-month observation period for patients enrolled in this study.
Re-Exposure Study
A common issue with biologics is that there may be a more pronounced immune response upon re-exposure to the biologic after a prolonged drug-free period. This can lead to reduced effectiveness of the biologic upon a later re-exposure to the drug, and potentially present safety issues. We conducted a re-exposure study in seven patients at four clinical sites that participated in KRYSTEXXA Phase I or Phase II development clinical studies. The goal of this re-exposure study was to determine whether patients who are re-exposed to intravenous KRYSTEXXA treatment after a prolonged KRYSTEXXA-free interval could tolerate the drug. The early development dose, schedule and number of KRYSTEXXA infusions as well of length of interval from last dose varied amongst these seven patients and none of these patients initially received the FDA-approved regimen. These patients had not received KRYSTEXXA treatment since participating in the Phase 1 or Phase 2 study in which they participated. The dosing phase of this study was completed and we evaluated the results of this small study which may be useful in the design of future clinical studies to better understand re-exposure after finite periods of KRYSTEXXA therapy.
Initial BLA Filings
In October 2008, we submitted our Biologic License Application, or BLA, to the FDA seeking approval to market KRYSTEXXA in the United States, and in December 2008, we were notified that the BLA was accepted with priority review status. In January 2009, the FDA notified us of the acceptance, subject to final approval, of the trade name KRYSTEXXA as the proprietary name for pegloticase.
In late January 2009, during the course of the FDA’s review of our BLA, we submitted amendments to our BLA to strengthen and clarify the data included in the BLA and to address review-related questions from the FDA. Although both the every two weeks dose regimen and every four weeks dose regimen for KRYSTEXXA met the primary efficacy endpoint in the Phase 3 trials, the every two weeks dose regimen, we believed, presented a much clearer path toward FDA approval due to its more robust risk-to-benefit profile. As a result, we focused exclusively on the every two weeks dose regimen and recommended only this dosage for approval with the amended BLA. We determined not to seek FDA approval for the every four weeks dose in the amended BLA.
The FDA determined that the amendments to the BLA constituted major amendments, and so the FDA elected under applicable procedures to extend its review period of the BLA for KRYSTEXXA by three months, establishing a revised Prescription Drug User Fee Act action, or PDUFA, date of August 1, 2009.
Complete Response Letter and Type A Meeting
On July 31, 2009, the FDA issued a Complete Response Letter, or CRL, notifying us that it was not in a position to approve the BLA as a treatment for chronic gout in patients refractory to conventional therapy unless and until a resubmission was provided to the FDA that addressed:
・deficiencies with the chemistry, manufacturing and controls, or CMC, section of the BLA,
・remediation of observations arising from the FDA pre-approval inspection of the manufacturing facility of our primary third-party API manufacturer, Bio-Technology General (Israel) Ltd, or BTG,
・a risk evaluation and mitigation strategy, or REMS, program (consisting of a Medication Guide and a Communication Plan), and
・a safety update focused on new clinical and pre-clinical data of KRYSTEXXA since the 120-Day Safety Update.One of the issues raised by the FDA in the CRL addressed a change in PEGylation concentration that we made in the proposed process for manufacturing pegloticase drug substance for commercial use of KRYSTEXXA final drug product. The FDA concluded that the comparability data that we submitted for the material manufactured using the proposed commercial manufacturing process was not adequate to demonstrate that it was representative of the material used to establish the safety and efficacy of KRYSTEXXA in the Phase 3 clinical trials. The FDA stated that we had the option of either reverting to and validating the manufacturing process used to produce pegloticase for the Phase 3 clinical trials or conducting additional comparability clinical trials to support the use of KRYSTEXXA manufactured using the proposed commercial manufacturing process.
The CRL also stated that the FDA determined that a REMS program would be necessary for KRYSTEXXA consisting of:
・a Medication Guide to ensure the safe and effective use of KRYSTEXXA by patients, alert and warn healthcare providers and patients about the risks of infusion reactions and anaphylaxis associated with KRYSTEXXA therapy, alert and warn healthcare providers not to use KRYSTEXXA in individuals with glucose 6-phosphate dehydrogenase, or G6PD, deficiency, and inform and educate healthcare providers to exercise caution when prescribing KRYSTEXXA to patients with major cardiovascular diseases,
・a Communication Plan directed to healthcare providers likely to prescribe KRYSTEXXA to provide for the dissemination of information about the risks of severe infusion reactions and anaphylaxis, severe events associated with the use of KRYSTEXXA in individuals with G6PD deficiency, and major cardiovascular events, and
・an Assessment Plan to survey patients’ and providers’ understanding of the serious risks of KRYSTEXXA.The CRL also included FDA comments on our draft label language as well as additional CMC comments focused on tightening a number of analytical methods used to assess manufacturing and narrowing analytical specifications associated with commercial production of pegloticase.
Following our review of the CRL, we requested a “Type A” meeting with the FDA, which occurred on September 14, 2009, to determine defined resolutions with respect to the necessary requirements for approval of our BLA. At this meeting, we gained clarification from the FDA on the contents of the CRL and proposed a resubmission plan to fully address all deficiencies and issues identified therein. In response to the deficiencies cited by the FDA with the CMC section of our BLA, we proposed to revert to and validate the original manufacturing process used to produce KRYSTEXXA drug product for the Phase 3 clinical trials and to make certain revisions, such as the inclusion of additional 0.2 micron filters, to the manufacturing process. The FDA indicated that, in its view, our plan was a reasonable approach that would be expected to produce pegloticase drug substance that is representative of that used to establish safety and efficacy in the Phase 3 clinical trials. The FDA also stated that it expected that the comparability between the material produced with this validated Phase 3 process that includes the additional filters and the Phase 3 clinical trial material used in the replicate clinical trials to establish safety and efficacy could be sufficiently established by quality criteria alone without the need to conduct additional clinical studies, provided no significant differences between products were observed.
The FDA also agreed at this meeting with the methods and criteria proposed by us to tighten a number of analytical methods used to assess manufacturing and acceptance criteria for all manufacturing steps in the final commercial production process for pegloticase. Additionally, the FDA informed us that the review cycle for resubmission of our BLA for KRYSTEXXA would include the review of all data to fully address all issues identified in the CRL, including the final product labeling and the materials to be used in connection with our REMS program for KRYSTEXXA. Since the resubmission included REMS program materials, it was subject to a Class 2 review cycle, meaning simultaneous approval of all components of our filing within six months of the date of resubmission.
Resubmission of BLA and FDA Approval of KRYSTEXXA
On March 15, 2010, we resubmitted our BLA for KRYSTEXXA to the FDA. The resubmission included data from three consecutive validation batches of pegloticase drug substance, additional and improved analytical methods for the control and release of pegloticase drug substance and KRYSTEXXA and other data which was designed to address the issues raised by the FDA in its July 31, 2009 CRL. Our submission also included a safety update from the remaining studies that were ongoing at the time of the previous 120-day safety update and additional documentation on prescribing and product labeling information, REMS program materials and a patient medication guide.
On March 30, 2010, the FDA acknowledged receipt of and accepted for review, our resubmitted BLA for KRYSTEXXA. The FDA deemed the resubmission a complete, class 2 response and established September 14, 2010 as the PDUFA date. On July 28, 2010, we submitted to the FDA the final three and six-month stability data for the pegloticase drug substance validation batches manufactured in late October 2009 and the final KRYSTEXXA drug product manufactured from those validation batches in November 2009. We submitted this data to the FDA in response to its request, made during our September 2009 “Type A” meeting, that we submit final stability data at least 30 days prior to the PDUFA date to provide the FDA with adequate time for review.
On September 14, 2010, the FDA approved KRYSTEXXA for marketing for the treatment of chronic gout in adult patients refractory to conventional therapy. We also received acceptance by the European Medicines Agency, or EMA, of the trade name KRYSTEXXA for the European Union.
【Manufacturing 】
We do not own or operate our own manufacturing facilities and use third-party contract manufacturers to manufacture our products under the oversight and supervision of our technical operations personnel. We intend to continue to rely on contract manufacturers to produce our products, and we have recruited personnel with manufacturing experience to oversee the production and release of KRYSTEXXA.
The manufacturing process for pegloticase, which is the API drug substance of KRYSTEXXA, consists of the production of uricase through a recombinant process in which a genetically-engineered bacteria produce uricase, followed by its purification, PEGylation, further purification and formulation to produce the bulk API, pegloticase, which we also refer to as the pegloticase drug substance. Pegloticase is then sterilized by filtration and is aseptically filled into sterile, single dose vials. The manufacturing process and the analytical methods used to test KRYSTEXXA and its intermediates have been validated as required by regulatory agencies.
All clinical supplies of the pegloticase drug substance were produced by BTG, and processes for the manufacture of the KRYSTEXXA drug product, namely sterilization and aseptic filling, were performed either by BTG, Wasserburger Arzneimittelwerk or Sigma-Tau PharmaSource, Inc., or Sigma-Tau. We have commercially launched KRYSTEXXA with pegloticase drug substance produced at BTG, and with aseptic filling and finishing performed by Sigma-Tau.
The production of the pegloticase drug substance is based on a recombinant micro-organism, the subject of an issued patent owned by Duke University, or Duke, and licensed exclusively to us, as well as published patent applications owned directly by us. The manufacturing processes used in the production of the pegloticase drug substance consist in most part of standard biotechnological techniques, except for the PEGylation step. The manufacturing process steps are covered by published patent applications owned directly by us and by an issued patent exclusively licensed to us by Mountain View Pharmaceuticals, or MVP.
On July 31, 2009, the FDA issued a CRL notifying us that it would not approve the BLA as a treatment for chronic gout in patients refractory to conventional therapy unless and until a resubmission was provided to the FDA that addressed, among other items, deficiencies with the CMC section of the BLA. The CRL also required correction of deficiencies and observations cited by the FDA during its June 2009 pre-approval inspection of BTG’s manufacturing facilities. While remediation of the deficiencies and observations arising from the FDA pre-approval inspection had been underway since the June 2009 inspection in accordance with two work plans submitted to the FDA by BTG in June and July 2009, in October 2009 the FDA provided notification that these original work plans were not adequate and identified additional corrective actions that would be required to successfully remediate the deficiencies and observations noted in their facility.
At our September 2009 “Type A” meeting with the FDA, we proposed a resubmission plan to fully address all deficiencies and issues identified in the CRL. Specifically, we proposed to revert to and validate the original manufacturing process used to produce KRYSTEXXA drug product for the Phase 3 clinical trials and to make certain revisions, such as the inclusion of additional 0.22 micron filters, to the manufacturing process. The FDA indicated that, in its view, our plan was a reasonable approach that would be expected to produce pegloticase drug substance that is representative of that used to establish safety and efficacy in the pivotal Phase 3 clinical trials. The FDA also agreed at this meeting with the methods and criteria proposed by us to tighten a number of analytical methods used to assess manufacturing and acceptance criteria for all manufacturing steps in the final commercial production process for pegloticase.
In late October 2009, as part of our validation campaign, we completed the manufacture of three consecutive batches of pegloticase drug substance at BTG using the manufacturing process used to manufacture pegloticase drug substance for the Phase 3 clinical trials. These batches were manufactured into final KRYSTEXXA drug product in November 2009 and samples from each batch were placed on stability testing by early December 2009. Our third-party testing laboratories then performed in-process and final release analytical testing on each batch of pegloticase drug substance and final KRYSTEXXA drug product to validate their comparability to the drug substance and final KRYSTEXXA drug product used in the Phase 3 clinical trials.
In November and December 2009, BTG submitted to the FDA reports of the steps that BTG had completed to that date with the goal of addressing the deficiencies and other observations identified by the FDA during its pre-approval inspection of BTG’s manufacturing facility in June 2009. In addition, BTG included in its submissions its plans and framework for implementing a broad, continuous quality improvement plan. In early February 2010, BTG received a letter from the FDA stating that the corrective actions implemented by BTG and the additional commitments made by BTG appear to address the FDA’s concerns. The FDA also stated in its letter that it will verify these corrective actions and additional commitments during the FDA’s next inspection of BTG’s facility.
On September 14, 2010, the FDA approved KRYSTEXXA for marketing in the United States for the treatment of chronic gout in adult patients refractory to conventional therapy.
We are advancing our efforts to complete the validation of manufacturing processes for the pegloticase drug substance by a second contract manufacturing organization, Merck Biomanufacturing Network, or Merck (previously Diosynth RTP), which is located in the United States. However, we will continue to rely on a single source of supply, BTG, for the pegloticase drug substance and NOF Corporation of Japan, or NOF, for mPEG-NPC, the PEGylation reagent. We have commenced efforts to engage a secondary fill and finish manufacturer for KRYSTEXXA, but at this time no contract agreement is in place for this function. As such, we also plan to continue to rely on a single provider of fill and finish services, Sigma-Tau, for the foreseeable future. In support of our plans to commercialize KRYSTEXXA, we have entered into agreements with BTG and Sigma-Tau for the supply of commercial materials and with NOF for supply of the PEGylation reagent.
BTG and Sigma-Tau commenced manufacturing of pegloticase drug substance and KRYSTEXXA drug product during the second half of 2010 pursuant to regularly scheduled commercial manufacturing campaigns. In connection with these manufacturing campaigns at BTG and the validation campaign at Merck, we have experienced some batch failures based on one manufacturing specification. While we believe these batch failures are within normal industry failure rates experienced for the commencement of biologic commercial manufacturing, this failure rate is nonetheless above the level that we believe to be acceptable for normal ongoing operations. With the assistance of an outside manufacturing and quality consulting firm, we have completed a review of these batches and believe that we have identified the root cause of these failures. Under our direction, BTG and Merck are in the process of implementing remediation steps that we believe will minimize or eliminate these batch failures in the future. While these remediation steps are ongoing, BTG has continued to manufacture pegloticase drug substance without batch failures. During the fourth quarter of 2010, BTG manufactured three batches of pegloticase drug substance that met all specifications.
For more information on our agreements with BTG, Merck, NOF and Sigma-Tau, please see “Manufacturing, Supply, Distribution and Other Arrangements”.
【Sales and Marketing 】
KRYSTEXXA became commercially available in the United States by prescription on December 1, 2010, when we commenced sales and shipments to our network of specialty distributors and wholesale distributors.
As KRYSTEXXA is an infused biologic, we expect that rheumatologists will be our primary target audience for our marketing and sales activities relating to KRYSTEXXA. Although the majority of gout patients are seen in primary care settings, many patients prefer specialized care by the rheumatologists. There are approximately 4,500 rheumatologists in the United States. Administration of biologic therapy via intravenous infusion is well-established in clinical practice in the rheumatology setting as there are two widely used pharmaceutical products used for the treatment of rheumatoid arthritis that are administered via intravenous infusion. The key opinion leaders in the gout field are rheumatologists, many of whom have been involved in the clinical development program for KRYSTEXXA.
Nephrologists see a high volume of complicated gout patients due to the association between the deposition of urate crystals in the kidney and renal disease. In some patients who undergo renal transplants, there can be an exacerbation of hyperuricemia and gout due to the use of medications to prevent organ rejection. A subset of nephrologists infuse biologics and do so in the hospital setting. We plan to market to these approximately 1,000 specialized nephrologists who we have determined have potential for adoption of KRYSTEXXA.
Infusion nurses play a critical role for any infused biologic product because they both perform the administration of a drug and are with the patient throughout the entire time of the infusion, providing a potential educational channel to patients. We also plan to market to infusion nurses for field force calls.
In preparation for the launch of KRYSTEXXA, we have conducted field force sizing analyses based on these target audiences and concluded on a field force of 60 specialty sales representatives for the commercial launch. Initially, these 60 sales representatives should allow us to target the approximately 4,500 rheumatologists, 1,000 nephrologists and 2,000 infusions centers which are either privately owned by the physician or are part of medical centers or academic centers. We have completed the hiring process for this field sales force and a management team. These employees have been fully trained and commenced field promotion on February 28, 2011. These field-based specialty sales representatives that we have hired have extensive experience in selling infused biologics, especially in the rheumatology field.
Additionally, we are contracting with a third party to provide 12 nurse educators who are experienced in the infusion of biologics to assist our field-based specialty representatives. These nurse educators will visit infusion centers and provide in service education to the healthcare nursing staff of these clinics. The in-service education will focus on proper storage and proper administration of KRYSTEXXA to patients. We also hired 12 additional employees to serve as reimbursement specialists. These Area Business Managers will provide assistance and education to the office or clinic staff, who are responsible for ensuring patients have reimbursement from the payors to provide services.
To support the payors, physicians and patients, we have also contracted for reimbursement services with an external organization that specializes in providing telephonic and web-based services in the area of insurance coverage and patient reimbursement. This company also administers our Patient Assistance Program pursuant to which we provide free prescriptions for patients who meet pre-established financial necessity criteria. In the first quarter of 2011, we expect to introduce a co-pay/co-insurance assistance program, pursuant to which we will offer need-based financial assistance to qualifying patients to help offset the costs associated with KRYSTEXXA treatment. We expect this program will be administrated by a third-party company that provides similar services for other biologic pharmaceutical companies. In conjunction with the commercial availability of KRYSTEXXA, on November 22, 2010, through partnerships with experienced third-party vendors, we launched our reimbursement and pharmacovigilance hotline services for the benefit and use of prescribers and patients.
Sales and Distribution
We sell KRYSTEXXA through a network of specialty and wholesale distributors. The specialty distributors market directly to doctors and infusion suites and include Besse Medical, McKesson Corp. and Curascripts. Our wholesaler customers market KRYSTEXXA primarily to hospitals and long-term care facilities and are Cardinal Health, AmerisourceBergen Corp. (the parent of Integrated Commercialization Services, Inc., or ICS, our third-party logistics provider) and McKessson Corp.
【Manufacturing, Supply, Distribution and Other Arrangements】
Bio-Technology General (Israel) Ltd. (a subsidiary of Ferring Pharmaceuticals)
In 2007, we entered into commercial supply and development agreements with BTG, pursuant to which BTG serves as the manufacturer and commercial supplier of the pegloticase drug substance for KRYSTEXXA and provides development, manufacturing and other services in relation to the product. Under the agreements, BTG also provided support with respect to our BLA for KRYSTEXXA. Pursuant to its terms, the development agreement automatically expired upon the FDA’s approval for marketing of KRYSTEXXA in the United States.
Under our commercial supply agreement with BTG, as amended, BTG is obligated to manufacture for us our firmly forecasted commercial supply of KRYSTEXXA and we are obligated to purchase from BTG at least 80% of our worldwide requirements of pegloticase drug substance. However, if BTG produces specified numbers of failed batches of pegloticase drug substance within one or more calendar quarters, then we may purchase all of our pegloticase drug substance requirements from other suppliers until BTG demonstrates to our reasonable satisfaction that it has remedied its supply failure. In addition, if our product forecasts are reasonably anticipated to exceed BTG’s processing capacity, then we may purchase from other suppliers our pegloticase drug substance requirements that exceed BTG’s capacity. We are obligated to provide BTG with a rolling forecast on a monthly basis setting forth the total quantity of pegloticase drug substance that we expect to require for commercial supply in the following 18 months. The first six months of each forecast represent a rolling firm irrevocable order, and we may only increase or decrease our forecast for the next 12 months within specified limits. As of December 31, 2010, based on our latest forecast, we expected to purchase an aggregate of approximately $7.5 million of pegloticase drug substance during 2011. During 2008, we paid to BTG non-refundable fees of $2.2 million, to reserve manufacturing capacity relating to our potential future orders of pegloticase drug substance. We recorded these capacity reservation fees, which may be credited as a discount against future orders of pegloticase drug substance, as research and development expenses as they were incurred.
Beginning in December 2015, which is the seventh anniversary of BTG’s first delivery of pegloticase drug substance under the commercial supply agreement, either we or BTG may provide three years advance notice to terminate the commercial supply agreement, effective not earlier than December 2018. The commercial supply agreement may also be terminated in the event of insolvency or uncured material breach by either party.
Merck Biomanufacturing Network
In 2007, we entered into a services agreement with Diosynth RTP, Inc (now a division of Merck), or Merck, pursuant to which Merck is preparing to serve as our secondary source supplier in the United States of pegloticase drug substance for KRYSTEXXA. Under the agreement, we are obligated to make specified milestone payments related to the technology transfer, and subsequent performance, of the manufacturing and supply process, which was initiated in August 2007 with BTG’s cooperation. In November 2009, we entered into a revised services agreement with Merck, pursuant to which we delayed the 2009 conformance batch production campaign until 2010. During the second quarter of 2010, the conformance batch production campaign at Merck was started. As a result of batch failures at Merck based on one manufacturing specification, the 2010 conformance batch production campaign was terminated during the fourth quarter of 2010. As such, this conformance campaign cannot be used to support licensure of the Merck facility for the commercial production of pegloticase drug substance. With the assistance of an outside manufacturing and quality consulting firm, we have completed a review of these batch failures and believe we have identified the root cause. Under our direction, Merck is in the process of implementing remediation steps that we believe will minimize or eliminate these batch failures in the future. We expect Merck’s conformance batch production to re-start later in 2011 and expect the additional costs associated with its re-execution campaign to result in incremental costs ranging between $7 million and $11 million. The timing of the conformance batch production and the expected campaign cost will be dependent on us reaching a satisfactory amendment to the service agreement.
We incurred total costs of $8.3 million and $8.2 million in 2010 and 2009, respectively, for services rendered under the agreement. Included in the total costs incurred in 2009 was a $2.0 million fee for the reservation of manufacturing capacity required for the production of the conformance batches in 2010 and an additional $2.5 million idle and down-time fee imposed under the agreement because we delayed the originally scheduled conformance batch production campaign from 2009 to 2010. We recorded the fees for capacity reservation, idle and down-time and other technology transfer services rendered by Merck as research and development expenses as they were incurred.
Either we or Merck may terminate the services agreement in the event of an uncured material breach by the other party. In addition, we may terminate the agreement at any time upon 45 days advance notice. If we terminate the agreement other than for Merck’s breach, or if Merck terminates the agreement for our breach, we must pay Merck a termination fee based on the value of the remaining unbilled activities under the agreement. Either party may also terminate the agreement within 30 days after any written notice from Merck that, in its reasonable judgment and based on a change in the assumptions or objectives for the project, it cannot continue to perform its obligations without a change in the scope, price or payment schedule for the project.
We estimate that Merck will be able to commence its commercial supply of pegloticase drug substance for KRYSTEXXA as our potential secondary source supplier during the second half of 2012, at the earliest. This estimate assumes that (1) the conformance batches are scheduled for production and testing in the second half of 2011, (2) the execution of validation batches will meet the same quality standards as those produced by BTG, (3) the Merck manufacturing facilities will receive a satisfactory inspection and regulatory approval from the FDA, and (4) we will complete and execute a commercial supply agreement with Merck. We and Merck will jointly make a go/no-go decision to have Merck proceed with commercial manufacturing following the evaluation of various preliminary manufacturing runs.
NOF Corporation (Japan)
In 2007, we entered into a supply agreement with NOF pursuant to which NOF serves as our exclusive supplier of mPEG-NPC, which is used in the PEGylation process to produce the drug substance for KRYSTEXXA. We must purchase our entire supply of mPEG-NPC from NOF unless NOF fails to supply at least 75% of our firm orders, in which case we may obtain mPEG-NPC from a third party until NOF’s supply failure is remedied to our reasonable satisfaction.
Under the agreement, we are obligated to make specified minimum purchases of mPEG-NPC from NOF. We must provide NOF with a rolling forecast on a quarterly basis setting forth the total quantity of mPEG-NPC that we expect to require in the following 18 months. The first six months of each forecast represent a rolling firm irrevocable order, and we may only increase or decrease our forecast for the next 12 months within specified limits. As of December 31, 2010, based on current forecasts, we expected to purchase mPEG-NPC at an aggregate cost of approximately $2.3 million during 2011. For any given year, upon three months advance notice, we may terminate our minimum purchase obligation for the entire year or the remainder of that year by paying NOF 50% of the minimum purchase obligation for that year or the remainder of that year.
NOF is obligated under the supply agreement to use commercially reasonable efforts to submit a Type II Drug Master File, or its equivalent, to the appropriate regulatory agency in one country outside the United States or in the European Union. Our agreement with NOF has an initial term ending in May 2017 and may be extended for an additional 10 years by mutual agreement of the parties at least 12 months before the expiration of the initial term. Prior to the expiration of the term, either we or NOF may terminate the agreement for convenience upon 24 months advance notice. Either we or NOF may terminate the agreement in the event of the other party’s insolvency or uncured material breach. In the event that NOF terminates the agreement for convenience or if we terminate the agreement for NOF’s breach or bankruptcy, we may require NOF to continue to supply mPEG-NPC for up to two years following the termination date. If we terminate the agreement for convenience or NOF terminates the agreement for our breach, we must pay NOF 50% of the minimum purchase obligation for the period from the termination date until the date on which the agreement would have expired.
Sigma-Tau PharmaSource, Inc.
In October 2008, we entered into a non-exclusive commercial supply agreement with Sigma-Tau (formerly known as Enzon Pharmaceuticals, Inc., which was acquired by Sigma-Tau in January 2010), which replaced our 2006 service agreement with Sigma-Tau. Under the terms of the commercial supply agreement, Sigma-Tau has agreed to fill, label, package, test and provide specified product support services for the final KRYSTEXXA product. In return, we agreed that once KRYSTEXXA received marketing approval from the FDA, we would purchase from Sigma-Tau product support services. As of December 31, 2010, we expected to purchase from Sigma-Tau product support services at an aggregate cost of approximately $1.7 million over the next 12 months. These purchase obligations are based on a rolling forecast that we have agreed to provide to Sigma-Tau on a quarterly basis setting forth the total amount of final product that we expect to require in the following 24 months. The first six months of each forecast will represent a rolling firm irrevocable order, and we may only increase or decrease our forecast for the next 18 months within specified limits. If we cancel batches subject to a firm order, we must pay Sigma-Tau a fee. Under the agreement, we are also obligated to pay Sigma-Tau a rolling, non-refundable capacity reservation fee, which may be credited against the fees for Sigma-Tau’s production of the final product. During 2010 and 2009, we incurred $0.5 million and $0.3 million, respectively, in capacity reservation fees. Capacity reservation fees incurred before FDA approval were recorded as research and development expenses, in the amount of $0.3 million for both 2010 and 2009. Capacity and reservation fees of $0.2 million incurred after FDA approval were recorded to the balance sheet in 2010. As a result of the grant by the FDA of marketing approval for KRYSTEXXA in the United States, we will no longer expense manufacturing costs relating to KRYSTEXXA as research and development expense. Instead, we will capitalize these costs as inventory as they are incurred.
Either we or Sigma-Tau may terminate the agreement upon 24 months advance notice given 30 days before each year’s anniversary date of the agreement. If we terminate the agreement, we would be obligated to pay Sigma-Tau a fee based on the previously submitted rolling forecasts. Either we or Sigma-Tau may also terminate the agreement in the event of insolvency or uncured material default in performance by either party.
We believe that our current arrangements for the supply of clinical and commercial quantities of pegloticase drug substance and finished form KRYSTEXXA will be adequate to satisfy our currently forecasted commercial requirements of KRYSTEXXA.
Mountain View Pharmaceuticals, Inc. and Duke University
We are party to an exclusive royalty bearing license agreement with MVP and Duke, originally entered into in August 1997 and amended in November 2001, granting us rights under technology relating to mammalian and non-mammalian uricases, and MVP’s technology relating to mPEG-NPC conjugates of these uricases, as well as patents and pending patent applications covering this technology, to make, use and sell, for human treatment, products that use this technology. These patents and pending patent applications constitute the fundamental composition of matter and underlying manufacturing patents for KRYSTEXXA. Under this agreement, we also have the exclusive license to the trademark Puricase ® , which is a registered trademark of MVP and was available for potential use as the proprietary name of the product candidate we now refer to as KRYSTEXXA. However, if we elect not to use the trademark Puricase, or if we otherwise fail to use the trademark Puricase within one year after the first sale of any product which uses the licensed technology, then MVP would retain all rights to use the trademark Puricase.
Under the agreement, we are required to use best efforts to bring to market and diligently market products that use the licensed technology. The agreement requires us to pay to MVP and Duke quarterly royalty payments within 60 days after the end of each quarter based on KRYSTEXXA net sales we make in that quarter. The royalty rate for a particular quarter ranges between 8% and 12% of net sales based on the amount of cumulative net sales made by us or our sub-licensees. Under the agreement, we are also required to pay royalties of 20% of any revenues or other consideration we receive from sub-licensees during any quarter. During the year ended December 31, 2008, we made aggregate milestone payments to MVP and Duke of $0.5 million upon the filing of our BLA for KRYSTEXXA. In addition, during the year ended December 31, 2010, we made aggregate milestone payments of approximately $0.8 million to MVP and Duke as a result of obtaining regulatory approval of KRYSTEXXA in the United States which was one of five major global markets identified in the agreement. We are also required to pay up to an aggregate of approximately $1.8 million to MVP and Duke upon the successful commercialization of KRYSTEXXA and attainment of specified KRYSTEXXA sales targets. As of December 31, 2010, we had made aggregate payments of approximately $2.5 million to MVP and Duke for the achievement of milestones under this agreement.
The agreement remains in effect, on a country-by-country basis, for the longer of 10 years from the date of first sale of KRYSTEXXA in such country, or the date of expiration of the last-to-expire patent covered by the agreement in such country. We may terminate this agreement in one or more countries with six months prior notice, and we may also terminate the agreement with respect to any country in which the licensed patents are infringed by a third party or in which the manufacture, use or sale of KRYSTEXXA infringes a third party’s intellectual property rights. Either we or the licensors may also terminate the agreement, with respect to the countries affected, upon the other party’s material breach, if not cured within a specified period of time, or immediately upon the other party’s third or subsequent material breach of the agreement or the other party’s fraud, willful misconduct or illegal conduct. Either party may also terminate the agreement for the other party’s bankruptcy or insolvency. Upon a termination of the agreement in one or more countries, all intellectual property rights conveyed to us with respect to the terminated countries under the agreement, including regulatory applications and pre-clinical and clinical data, revert to MVP and Duke and we are permitted to sell off any remaining inventory of KRYSTEXXA for such countries.
【Reimbursement and Pricing Controls】
In many markets today, including the United States as well as other markets in which we or any potential collaborator would commercialize KRYSTEXXA if we obtain marketing approval to do so, the prices of pharmaceuticals are constantly being subjected to direct and indirect price controls by a multitude of laws and reimbursement programs with varying price control mechanisms. In addition, where pricing of a pharmaceutical product varies from jurisdiction to jurisdiction, parallel importing in which product sold at a lower price in one jurisdiction may be legally or illegally imported into higher priced jurisdictions may undercut pricing in that higher priced jurisdiction.
Since we set the price for KRYSTEXXA at $2,300 per 8 mg vial, private and public payors are determining their interest in providing access to KRYSTEXXA. They are also determining what requirements or hurdles, such as prior authorization, to put in place for patients to qualify for therapy and ultimately what level of reimbursement they will provide, as well as the level of contribution required from the patient. These access decisions are closely linked to the price of KRYSTEXXA and our ability to demonstrate clinical and economic benefits for a payor’s covered populations.
Given that KRYSTEXXA is an orphan drug targeting a relatively small patient population without alternative approved therapies, we expect that KRYSTEXXA will be reimbursed by most major plans. However, we anticipate usage to be restricted to approved labeling or any relevant published treatment guidelines. In the United States, we expect limitations to be imposed through prior authorization and possibly through step therapy, by which patients would be required to fail both allopurinol and febuxostat before KRYSTEXXA would be reimbursed. We expect KRYSTEXXA to be covered mainly as a medical benefit as it will be administered by healthcare professionals in medical specialist offices, hospital infusion suites and independent infusion centers.
In the European Community, governments influence the price of pharmaceutical products through their pricing and reimbursement rules and control of national health care systems that fund a large part of the cost of those products to consumers. Some jurisdictions operate positive and negative list systems under which products may only be marketed once a reimbursement price has been agreed. Other member states allow companies to fix their own prices for medicines, but monitor and control company profits. The downward pressure on health care costs in general, particularly prescription drugs, has become very intense. As a result, increasingly high barriers are being erected to the entry of new products.
【Patents and Proprietary Rights】
Our scientific staff, contract manufacturing partners and consultants continually work to develop proprietary techniques, processes and products. We protect our intellectual property rights in this work by a variety of means, including assignments of inventions from our scientific staff, contract manufacturing partners and consultants, and filing patent and trademark applications in the United States, Europe and other major industrialized countries. We also rely upon trade secrets and improvements, unpatented proprietary know-how and continuing technological innovation to develop and maintain our competitive position.
As of February 24, 2011, we maintained 22 issued U.S. patents either owned or exclusively licensed by us, and 108 foreign issued patents in a number of jurisdictions. Additionally, as of February 24, 2011, we owned or have exclusively licensed to us, 5 issued U.S. patents, 11 pending U.S. patent applications, 90 issued foreign patents and 145 pending foreign patent applications in a number of jurisdictions in support of KRYSTEXXA. However, our patent applications might not result in issued patents and issued patents might be circumvented or invalidated. The expiration or loss of patent protection resulting from legal challenge normally results in significant competition from generic products against the originally patented product and can result in significant reduction in sales of that product in a very short time. For example, generic competition for Oxandrin began in December 2006 and the introduction of generic products has caused a significant decrease in our Oxandrin revenues, which has had an adverse affect on our financial results and cash flow. We believe that important legal issues remain to be resolved as to the extent and scope of patent protection, and we expect that in certain cases litigation may be necessary to determine the validity and scope of our and others proprietary rights. Such litigation may consume substantial amounts of our resources.
We are aware of patents and patent applications issued to and filed by other companies with respect to technology that is potentially useful to us and, in some cases, related to products and processes being developed by us. We cannot currently assess the effect, if any, that these patents may have on our operations.
In the aggregate, our patent and related rights are of material importance to our business. We have exclusively licensed from MVP and Duke issued patents and pending patent applications in numerous countries worldwide, including the United States, all of the countries included in Europe, China and Japan, directed to PEGylated urate oxidase, as well as methods for making and using PEGylated urate oxidase. We have also jointly filed U.S. patent applications with Duke directed to administration of PEGylated urate oxidase. In addition, we are the sole owner of several pending patent applications filed in numerous countries worldwide, including the United States, all of the countries included in Europe, China and Japan, directed to urate oxidase. Our licensed, co-owned and solely-owned issued patents and pending patent applications relating to PEGylated urate oxidase, if issued, would expire between 2019 and 2026, not including any possible patent term extensions that may be available as a result of the recent FDA approval on September 14, 2010 of KRYSTEXXA for marketing in the United States.
【Competition】
On September 14, 2010, we received FDA approval for marketing of KRYSTEXXA in the United States as a treatment for chronic gout in adult patients refractory to conventional therapy. There is no other drug or biologic approved for this patient population. Currently, by far the most prevalent conventional treatment for patients with gout is allopurinol, which can lower uric acid levels by inhibiting uric acid formation. Additionally, a small number of gout patients are treated with probenecid, which can lower uric acid levels by increasing excretion of uric acid. Febuxostat is another treatment for gout that received FDA approval in February 2009 and was launched in the U.S. market in March 2009 under the trade name Uloric ® . Febuxostat can lower uric acid levels by inhibiting uric acid formation through the same mechanism of action as allopurinol. Although febuxostat at the 80 mg dose has demonstrated superior uric acid control as compared to the most commonly used dose of allopurinol in randomized head-to-head clinical trials, febuxostat has not demonstrated superior clinical benefits in comparison to allopurinol. If febuxostat is able to adequately treat some gout patients who are unable to be adequately treated by allopurinol, it will reduce the population of patients with chronic gout that is refractory to conventional therapy and therefore our target market. Febuxostat was developed by Teijin Pharma Limited in Japan and licensed to Takeda Pharmaceuticals North America, Inc. in the United States and to Ipsen Pharmaceuticals, or Ipsen, in Europe. In October 2009, Ipsen subsequently granted exclusive license rights in 41 countries to the Menarini Group.
In addition to the drugs which are currently on the market that treat patients with gout, there are companies who are developing new medications for the gout market. Ardea Biosciences is currently developing RDEA594 for the treatment of hyperuricemia and gout. This product candidate recently generated positive results from a Phase 2a study to show normalization of the amount of uric acid excreted by gout patients previously classified as under-excretors. As this product is still in mid-stage development, it is uncertain if this drug candidate will be approved for marketing by the FDA alone, or in combination with other products, in the future.
Legislation has been introduced in the U.S. Congress that, if enacted or implemented, would permit more widespread reimportation of drugs and biologics from foreign countries into the United States. This may include reimportation from foreign countries where the drugs are sold at lower prices than in the United States. Such legislation, or similar regulatory changes, if enacted, could be an additional competitive factor for any approved products that we market. Legislation also has been introduced in the U.S. Congress that, if enacted, would permit the FDA to approve biosimilar versions of biological products like KRYSTEXXA through an abbreviated approval pathway. Such legislation, or similar regulatory changes, if enacted could result in earlier entry of similar, competing products and be another competitive factor for KRYSTEXXA.
[2006] P3段階 [COMPETITION 2006] If and when commercialized, Puricase will be launched in the gout treatment-failure population, an indication for which there is currently no product commercially available. Products used to treat the symptoms of gout, such as gout flares and synovitis, could be used concomitantly in patients also using Puricase, as long as symptoms and signs of the disease persist. Other uric acid lowering therapies, such as probenecid, oxypurinol, and allopurinol, have not been tested for use in combination with Puricase. Puricaseは Mountain View Pharmaceuticals, Inc.により創製され、1998.8.17にSavientに全世界ライセンスを与えた。
●Savient Pharmaceuticals, Inc. ●Pipeline KRYSTEXXA®(pegloticase)[旧Puricase] P3 痛風 Oxandrin® (oxandrolone) 術後等体重回復補助剤 ■Investor Relations ●SEC Filings 10-K annual report[2011.3.1] 10-K annual report[2010.3.1] 10-K annual report[2009.3.2] 10-K annual report[2008.3.14] 10-K annual report[2007.3.16] ●Annual Report ●Press Releases Savient Pharmaceuticals Marketing Authorization Application for KRYSTEXXA® Accepted for Review by European Medicines Agency[2011.5.26]
Savient Pharmaceuticals Submits European Marketing Authorization Application for KRYSTEXXA®[2011.5.4]
Savient Pharmaceuticals Announces U.S. Launch of KRYSTEXXAmV; Reports Fourth Quarter and Year-End 2010 Financial Results[2011.2.25]
Savient Pharmaceuticals Announces First Shipment to Specialty Distributors in the United States and Pricing of KRYSTEXXAmV[2010.11.30]
Savient Pharmaceuticals Announces Expected Availability of KRYSTEXXAmV for Prescription and Reports Third Quarter 2010 Financial Results[2010.11.4]
FDA Approves KRYSTEXXA(TM) (pegloticase) for the Treatment of Chronic Gout in Adult Patients Refractory to Conventional Therapy[2010.9.14]
Savient Announces KRYSTEXXA(TM) Resubmitted BLA Accepted for Review by the FDA[2010.3.30]
Savient Resubmits Biologics License Application for KRYSTEXXA(TM) (pegloticase) for the Treatment of Chronic Gout in Patients Refractory to Conventional Therapy[2010.3.15]
Savient Provides Update on KRYSTEXXA(TM) BLA Resubmission Activities[2010.1.8]
Savient Provides Update on Meeting with U.S. Food and Drug Administration for KRYSTEXXA(TM)[2009.9.16]
Multiple Abstracts Related to KRYSTEXXA(TM) Development and Treatment Failure Gout to be Presented at the 2009 ACR/ARHP Annual Scientific Meeting[2009.9.8]
Savient Pharmaceuticals Receives Complete Response Letter from U.S. Food and Drug Administration for KRYSTEXXA(TM)[2009.8.2]
FDA Appointed Arthritis Advisory Committee Recommends U.S. Food and Drug Administration Approval for KRYSTEXXA(TM) for Refractory Chronic Gout[2009.6.16]
Savient Announces New Date for FDA Arthritis Advisory Panel Review of KRYSTEXXA(TM) for Treatment Failure Gout[2009.5.7]
Savient Announces FDA's Advisory Panel to Review Pegloticase for Treatment-Failure Gout Patients[2009.1.28]
Savient Announces Completion of Patient Enrollment in Phase 3 Trials of Puricase(R) for Treatment-Failure Gout[2007.3.6]
New Poll Shows the Extreme Pain of Gout is Detrimental to Quality of Life & Work[2006.11.9]
- 痛風調査結果
Savient's Puricase(R) (PEG-uricase) Phase 2 Results Show Powerful Anti-hyperuricemic Activity in Treatment-Failure Gout Patients[2006.6.22]
Savient's PuricaseR (PEG-uricase) Substantially Reduces and Sustains Lower Plasma Urate Levels in Patients with Treatment-Resistant Gout[2005.11.14]
■Schwarz Pharma AG[ドイツ]
- http://www.schwarzpharma.com/ 1946年創立。ドイツ。 年間売上(2003)EURO 1,496.3 Million、従業員数3,853 1980 nitroglycerin dinitrate 'Isoket' (since 1963)の開発から the mononitrate 'Elantan' (1981) and the nitroglycerin patch 'Deponit' (1983) が発売してきた。 同じ循環器分野で A calcium antagonist ('Cardibeltin', 1980), then an ACE inhibitor ('Tensobon', 1983) and finally a prostaglandin ('Prostavasin', 1985)を発売。 2005 rotigotineの全権利をAderis Pharmaceuticals Inc., USAから Euro 63.3mで獲得。 2006.3 Pfizerに過活動膀胱薬fesoterodine(欧米申請中)の全権利を売却、up-front and milestone payments of Euro 89.8m 2006.9 UCB Groupとの事業統合契約調印。 その後UCBがSCHWARZ PHARMA株総数の87.6%を取得。 ★決算2006 ・Neupro(R) (rotigotine transdermal patch)(Rotigotine CDS;SPM 962) 抗パーキンソン病薬 - 2005.3.29 FDA申請。 EMEA申請は2004.9.29。新dopamine agonistで1日1回皮膚パッチ。 1998年にAderis Pharmaceuticals, Inc., USAから世界の開発・販売権を取得。 - 単独療法のEU 2006.2承認後、2006.3独・英発売に続き欧州12ヵ国で発売。 2007.1に進行性パーキンソン病での Levodopa併用で承認。 米国承認は2007.半ば予定。 抗パ剤世界市場規模はUS$2.9bn、年成長率8%。 Restless Legs Syndrome (RLS)の適応拡大:P3で欧米申請は2007.半ば予定。 RLS剤世界市場規模はUS$350mn、年成長率29%。 ・Lacosamide P3 新世代抗てんかん剤 抗てんかん剤世界市場規模はUS$12.4bn、年成長率7%。 副作用が少なく、効果が大きく、intervene in the disease process, slowing down or even stopping the progressionof the disease. Diabetic neuropathic painへの適応拡大(P3):世界市場規模はUS$3.5bn、年成長率14%。 ●会社決算[経営 2007] ・中止事業～UCBとの合併に伴いも2007.12.28時点で外国子会社１３社をUCBに移籍。 (米・英・仏・伊・スイス・西・蘭・ポーランド・オーストリア・フィンランド・ デンマーク・スエーデン・ノルウェイ) [経営 2004] ・大幅減収は、omeprazole(米国Univasc)にジェネリック品が多く参入したため。 ●地域別売上高
(Euro milllion) 2007 2006 2005 2004 2003 2002 2001 2000 純売上高 327.331 362.132
旧1,000.4990.6 946.6(-36.7) 1496.3 963.5 767.7 736.2 営業利益 (8.538) (4.209)
旧49.5-17.0 15.8 260.5 74.9 16.6 -3.6 純利益 871.906 13.079
旧12.4-54.1 -0.8(-98.6) 132.5 48.4 40.5 13.6 中止事業損益 946.698 19.207 研究開発費 89.985 126.758
旧215.1258.9 198.3(+33.4) 144.0 124.2 107.0 91.5 従業員数 3,714 4,327 4,100 3,813 3,853 3,739 ※[2004構成比] 米国43%、欧州32%、独22%、アジア3% ●製品売上
(Euro milllion) 2007 2006 2005 2004 2003 2002 2001 2000 純売上高 327.331 362.132
旧1,000.4(+1.0)990.6(+4.6) 946.6(-36.7) 1496.3 963.5 767.7 736.2 独 317.177 375.404 他の欧州 45.905 34.043
旧512.6(-1.9)522.4(+1.9) 560.3(+2.7) 545.4 米国・アジア 37.518 37.523
旧487.8468.2 433.9(-56.2) 991.0 米国 0 0
旧450.3(+3.9)433.2(+7.5) 402.9(-58.2) 963.7 アジア 37.518 37.523 FROM Annual Report 2004[pdf,122p] - 個別製品売上 109p(Leading SCHWARZ PHARMA Products) ●開発品目-主要
(Euro milllion) 2007 2006 2005 2004 2003 2002 備考 ★循環器 Isoket/Dilatrate 50.1 52.2 48.6 48.8 51.7 Isosorbide Dinitrate/心臓病[CHD] 独 [] 他の欧州(CIS) 16.7(-11.2) [] Provas/Miten 25.4(-31.9) 45.7 43.7 40.1 33.3 27.8 [Valsartan] /高血圧 独 25.4(-31.9) [] 他の欧州 [] Elantan 10.7(+0) 43.8 43.3 43.9 44.0 46.8 Isosorbide Mononitrate/心臓病[CHD] 独 [] 他の欧州 10.7(+-0) [] Prostavasin 43.5 41.2 37.7 35.6 42.2 Alprostadil /Peripheral Arterial Occlusive Disease Verelan PM 43.6 42.0 50.5 38.3 36.7 Verapamil HCL /高血圧 Deponit 8.7(+14.1) 33.8 36.6 40.7 36.1 37.0 Glyceryl Trinitrate (Patch) /心臓病[CHD] 独 [] 他の欧州 8.7(+14.1) [] Univasc / Femipres 35.7 38.7 13.8 27.4 56.3 Moexipril /高血圧 Uniretic / Femipres Plus 25.5 23.7 22.3 21.6 16.9 Moexipril HCTZ /高血圧 Clivarina 12.7 12.0 12.0 10.5 8.2 Reviparine Sodium /静脈血栓 Cardin - 9.4 6.3 Simvastatin /脂質低下剤 ★消化器 Omeprazol (KUDCo) 191.6 184..3 229.2 784.3 176.3 Omeprazole /消化性潰瘍、逆流性食道炎 Rifun 39.9 52.1 39.0 34.2 35.8 Pantoprazole /消化性潰瘍、逆流性食道炎 独 3.9(-90.3) [] 他の欧州 [] Glycolax 44.6 52.2 17.9 0.0 - Polyethylen glycol /便秘 Colyte 23.2 19.0 18.7 15.8 17.1 Polyethylene Glycol,Sodium Chloride /Bowel cleaning prior to colonoscopy Procto 16.6 12.1 13.0 16.4 18.0 Hydrocortisone /Dermatoses Vogalene 12.3 10.4 10.2 8.9 7.5 Metopimazine /吐き気Nausea Levsin 8.7 11.3 16.5 19.3 Hyoscyamine /Irritable Bowel Syndrome Dioctyl 6.1 4.9 [Docusate]便秘 Norpramin - 10.4 13.7 Omeprazole /消化性潰瘍、逆流性食道炎 ★中枢神経系 Agit / Seglor 12.7 13.1 14.8 12.8 12.0 Dihydroergotamine 片頭痛 Niravam 13.5 3.6 0.0 [Alprazolam]不安症 Neupro 16.5 9.5 - [Rotigotineパッチ]パーキンソン病 独 16.5 [] 他の欧州 [] Tylex 8.0 9.5 11.1 11.2 14.2 Paracetamol, Codeine 痛み Primesin 5.7 5.5 5.8 [Fluvastatin]関節炎 Parcopa 6.1 2.5 0.2 [Carbidopa/Levadopa]パーキンソン病 Lorans 4.5 5.0 7.7 7.3 8.4 Lorazepam /不安症 ★泌尿器 Viridal / Edex 19.6 17.7 12.3 13.9 11.9 Alprostadil /勃起不全 Spasmo-Lyt 5.0 4.7 5.7 Trospium Chloride 尿失禁 Mitem 3.6 3.6 0.0 - mitomycin 癌 ★その他 Atmadisc 47.8(+1.5) 47.1 44.4 36.3 29.6 27.7 Salmeterol Xinafoate&fluticasone /喘息 独 47.8(+1.5) [] 他の欧州 [] Ferro Sanol 10.5(+1.5) 29.8 24.8 22.2 19.8 18.0 Iron (II)-Glycine-Sulphate Complex /鉄欠乏症 独 [] 他の欧州 10.5(+1.5) [] Oestradiol 8.6 4.3 [Estradiol]Estrogen substitution 独 [] 他の欧州 [] [] FROM Annual Report 2007[pdf,141p] -p94 ●開発品目-リスト除外
製品 適応 ステージ 備考 Rotigotine Nasalspray acute intervention for Restless Legs Syndrome (RLS) IIa Rotigotine CDS Restless-Legs-Syndrome 米欧申請2007Q4 市場規模US$500Million Vimpat(R)(Lacosamide)(旧Harkoseride) Epilepsy EU申請2007.5
FDA申請2007Q4Vimpat(R)(Lacosamide)(旧Harkoseride) Diabetic Neuropathic Pain EU申請2007Q3
FDA申請2007Q4市場規模US$3Billion Toviaz(R)(Fesoterodine) OAB/Urinary Incontinence 欧承認済み
FDA2007.1 approvable letter2006春Pfizerに全世界権売却
an anti-muscarinic agent
市場規模US$2BillionNeupro(R)(Rotigotine transdermal system)
(Rotigotine CDS;SPM 962)Parkinson's Disease FDA申請2005.3.29、FDA承認2007.5。 EMEA申請2004.9.29、EMEA承認2006.2 EMEA承認2006.2(For the treatment of the signs and symptoms of early-stage idiopathic Parkinson's disease as monotherapy)、EU27ヵ国には英独2006.3発売に続く。 新dopamine agonistで1日1回皮膚パッチ。1998年にAderis Pharmaceuticals, Inc., USAから世界の開発・販売権を取得。
製品 適応 ステージ 備考 Pamirosin (SPM 969) Benign Prostatic Hyperplasia P2 unclear preclinical findingsにより開発中止[2004.11]
●Schwarz Pharma AG ●Products ●Investor Relations [Preliminary Report 2003] SCHWARZ PHARMA’s Results Exceed Expectations, Pipeline Advanced[2004.2.18;pdf,4p] ★Business Report -Annual Reports Annual Report 2007[pdf,141p] - Annual Report 2006 - [pdf,196p] - 個別製品売上 187p(Leading SCHWARZ PHARMA Products) - 開発製品 20-22p(Products in Clinical Development) Annual Report 2005 - [pdf,150p] Annual Report 2004[pdf,122p] - 個別製品売上 109p(Leading SCHWARZ PHARMA Products) - 開発製品 6-11p(Development projects to reach market) Annual Report 2003[pdf,109p] - 個別製品売上 91p(Leading SCHWARZ PHARMA Products) - 開発製品 8-11p(Major Advances in Development Projects) ●Press Room -Press Releases Full Year Report 2007[2008.2] Full Year Report 2006: Sound Business Trend [2007.2] Executive Board and Supervisory Board recommend SCHWARZ PHARMA Shareholders Acceptance of Offer by UCB[2006.11.20] - ドイツSchwarz Pharma AGはベルギーのUCB社による44億ユーロ（56億ドル）での買収提案に合意。 社名はそのまま。 SCHWARZ PHARMA Acquires Remaining Rights to Rotigotine from Aderis[2005.7] - 1998年にAderis Pharmaceuticals, Inc., USAから世界の開発・販売権を取得。 抗パーキンソン病薬RotigotineはFDA/EUに申請済み。 SCHWARZ PHARMA’s NDA for Rotigotine Transdermal System is filed by FDA[2005.3] - 2005.3.29 FDA申請。 EMEA申請は2004.9.29。 SCHWARZ PHARMA discontinues clinical trial in benign prostate hyperplasia[2004.11] - unclear preclinical findingsにより、pamirosin(SPM969)の開発中止 SCHWARZ PHARMA to Add Promising Novel Treatment Option for Pain to Its Pipeline[2004.2] - AmorePacific Corp[韓国]からVR1 (vanilloid) receptor antagonistsのPAC20030 と関連物質のライセンス契約。 韓国とインドを除く全世界の権利。 慢性疼痛を 適応として現在前臨床。2005年末に臨床試験開始予定。 -------------------------------------------------
- 07/2007 - First Half Year Report 2007
- 07/2007 - UCB announces The U.S. Launch of Neupro® (Rotigotine Transdermal System) for the Treatment of Early-Stage Parkinson's Disease
- 07/2007 - Stephan Roeder appointed as new Chief Financial Officer of SCHWARZ PHARMA AG
- 07/2007 - Domination and Profit Transfer Agreement between SCHWARZ PHARMA and UCB Effective
- 05/2007 - SCHWARZ PHARMA Submits Marketing Application for it's Epilepsy compound Lacosamide
- 05/2007 - FDA Approves SCHWARZ PHARMA's Neupro for the Treatment of early-stage Parkinson's Disease in USA
- 05/2007 - Jürgen Baumann leaves SCHWARZ PHARMA
- 04/2007 - First Quarter Report 2007
- 04/2007 - SCHWARZ PHARMA Announces Publication of Rotigotine Data for Advanced Parkinson's Disease in Neurology
- 04/2007 - Rotigotine Study to Investigate 24-hour-Action and Sleep Benefits in Parkinson's Patients
- 03/2007 - Domination and Profit Transfer Agreement
- 02/2007 - Full Year Report 2006: Sound Business Trend
- 02/2007 - Positive Results with Lacosamide in Diabetic Neuropatic Pain in Phase III trial
- 02/2007 - Changes in the Supervisory Board of SCHWARZ PHARMA
- 01/2007 - Neupro Now Approved in Europe for All Stages of Parkinson's Disease
- 01/2007 - Principle Decision on Group Integration of SCHWARZ PHARMA by Domination and Profit Transfer Agreement
- 01/2007 - Positive Results with Rotigotine in Restless Legs Syndrome in Second Phase III trial
- 12/2006 - Changes within the Executive Board of SCHWARZ PHARMA AG
- 12/2006 - SCHWARZ PHARMA announces agreement with OTSUKA for jointly marketing Pletal(R) in Germany
- 11/2006 - Executive Board and Supervisory Board recommend SCHWARZ PHARMA Shareholders Acceptance of Offer by UCB
- 11/2006 - Neupro(R) Receives Positive Opinion from European CHMP for the Treatment of Advanced Parkinson's Disease
- 11/2006 - Lacosamide Has a Novel Dual Mode of Action
- 10/2006 - Nine Months Report 2006: Business on Track, Further Progress in R&D
- 10/2006 - Positive Results for Lacosamide in Second Phase III Epilepsy Trial
- 10/2006 - SCHWARZ PHARMA Reports Positive Results for Rotigotine in Restless Legs Syndrome
- 09/2006 - SCHWARZ PHARMA's Parkinson Patch Offers Additional Benefits
- 07/2006 - Half Year Report 2006: SCHWARZ PHARMA on Track
- 07/2006 - SCHWARZ PHARMA Filed Application for Neupro in Advanced Parkinson's Disease with EMEA
- 06/2006 - US FTC Clears SCHWARZ PHARMA's Agreement with Pfizer for Fesoterodine
- 04/2006 - First Quarter Report 2006: SCHWARZ PHARMA with a Good Start
- 04/2006 - SCHWARZ PHARMA and Pfizer Enter into Worldwide Transaction and Settle Fesoterodine Litigation
- 04/2006 - SCHWARZ PHARMA Presents Phase III Data on Fesoterodine at the EAU Congress
- 04/2006 - SCHWARZ PHARMA to present Lacosamide Data in Neuropathic Pain on the AAN Congress in San Diego
- 04/2006 - SCHWARZ PHARMA Presents Clinical Data on Rotigotine Transdermal Patch at the Annual Meeting of the American Academy of Neurology
- 03/2006 - Lacosamide at Significance Level in Diabetic Neuropathic Pain Phase III Trial
- 03/2006 - Positive Phase III Results for Lacosamide in Epilepsy
- 03/2006 - Neupro(R) Receives Approvable Letter from FDA for Early Parkinson's Disease in USA
- 02/2006 - Neupro(R) Approved in Europe for the Treatment of Early Parkinson's Disease
- 02/2006 - Full Year Report 2005
●Research & Development ★Our Development Pipeline
●SCHWARZ PHARMA Inc.[US] - http://www.schwarzusa.com/ ●Products ●Press Room - Press Releases
■Sepracor Inc.
- http://www.sepracor.com/; 研究開発型製薬企業。 米マサチュセッツ州。 1984 創立。 by Mr.Timothy J. Barberich(現在も前CEOとして役員) ; ●[NY Times 2008.11.8]INVESTING IT; A Small Drug Maker In a Low-Risk Niche 1989 世界的品目の異性体や代謝物の製品化開発に特化。 1991 株式公開 1994 子会社BioSepra Inc.(医薬製造クロマトグラフィ技術開発)を設立。 その後同社はchromatography事業を売却し、仏BioSphere Medical, S.A.を買収し 社名をBioSphere Medical, Inc.に変更。 1994 子会社HemaSure Inc.(輸血用血液濾過技術)を設立。 2001.5 HemaSure Inc.の全資産をWhatman Bioscience Inc(Whatman plc子会社)に売却。 2001.12 HemaSure Incは社名をHMSR, Incに変更。 2002.3 HMSR, IncはPoint Therapeutics, Incに吸収合併された。 1995.5子会社Versicor, Inc.(感染症の創薬)を設立。 同社は2000.8に株式公開。 2009.9.3 大日本製薬かSepracor社を買収(総額U.S. $2.6 Billion) - [日本語] - [説明資料] 年間総収入$1,225 million、製品売上$1,177 milion(2007), 従業員数2,277 セプラコール社は異性体開発に特化することで失敗リスクを低減した創薬ベンチャーの成功モデル。 発売製品については、導出３製品、自社販売３製品がいずれも各領域で重要な位置を占めている。 しかし、開発中の製品を含めて、最近開発方針を変更した。 既に製品導入を開始、異性体にこだわらない開発を進めるようになった。 大手企業へのライセンス品目 Schering-Plough for CLARINEX(R)(desloratadine); Sanofi-Aventis for ALLEGRA(R)(fexofenadine HCl); and UCB Farchim SA for XYZAL(R)/XUSAL(TM) (levocetirizine). ●会社決算●製品売上
($000) 2007 2006 2005 2004 2003 2002 2001 2000 収入 製品売上高 1,177,256 1,149,374
旧1,162,775769,685 319,781 286,819 190,227 125,248 57,160 ロイヤリティ 47,710 33,759 51,243 52,150 51,487 48,491 25,663 2,573 共同研究開発 - - - - - - - 3,573 ライセンス料 264 - - 8,946 5,734 250 1,184 21,939 総収入 1,225,230 1,183,133
旧1,196,534820,928 380,877 344,040 238,968 152,095 85,245 原価及び経費計 1,085,542 927,281
旧1,032,017838,545 584,818 449,349 450,569 378,568 283,491 売上原価 117,155 104,736 67,431 35,427 30,219 24,609 15,904 14,334 販売管理費 699,336 691,650
旧763,793626,610 389,417 198,906 180,905 131,386 98,398 研究開発費 263,756 163,488 144,504 159,974 220,224 243,797 231,278 170,759 営業利益 22,533 151,116
旧164,517(16,573) (202,689) (103,323) (207,301) (226,473) (198,246) 経常利益 64,603 174,817
旧188,2184,078 (296,910) (137,922) (280,790) (226,167) (207,637) 純利益 58,333 171,161
旧184,5623,927 (296,910) (137,922) (280,790) (224,015) (204,017) 従業員数 2,277 2,470 2,059 1,782 983 818 930 499 ●研究開発費内訳 LUNESTA (eszopiclone) 25,074
累245,09720,301
累220,02316,159
累199,72247,833
累183,56320,206
累135,730XOPENEX HFA (levalbuterol tartrate) 6,209
累175,50712,507
累169,29824,094
累156,79121,934
累132,69753,367
累110,763BROVANA (arformoterol tartrate) 14,837
累188,76812,353
累173,93118,059
累161,57825,395
累143,51944,712
累118,124SEP-225289 11,083
累24,1939,041
累13,1103,951
累4,069- - SEP-227162 12,844
累20,9846,394
累8,1401,746
累1,746- -
($ 000) 2007 2006 2005 2004 2003 2002 2001 2000 1999 備考 ●製品売上計 1,177,256 1,162,775(+51) 769,685(+141) 319,781(+11.5) 286,819(+51) 190,227 125,248 57,160 16,383 Xopenex Inhalation 487,189 542,944
旧554,999(+30)410,807
旧428,506(+34)319,781(+11.5) 286,819 190,227 122,200 55,100 14,100 (発売1999.5)levalbuterol HCl Xopenex HFA 74,883 40,994
旧40,968(+243)11,958(-) 0 - - - - - (発売2005.12)levalbuterol HCl;MDI剤型 Lunesta 600,904 565,436
旧566,808(+72)327,100
旧329,221(-)0 - - - - - (発売2005.4)eszopiclone 睡眠薬 Brovana 14,280 - - 発売2007.4(米) [arformoterol tartrate]喘息 対総収入比 96% 97% 94% 84% 83% 80% 82% 67% 72% ●Royalty収入計 47,710 33,759 51,243 52,150 51,487 48,491 25,663 2,573 2,000 Clarinex 16,500 12,197 9,364 13,320 15,633 12,370 (発売2002.1) (Desloratadine)Schering-Plough Allegra 25,200 16,593 36,945 35,005 34,697 35,504 25,254 2,495 1,746 (fexofenadine HCl) Sanofi-Aventis;発売1996.10 XYZAL/XUSAL 6,000 4,969 4,933 3,734 1,127 617 409 (発売2001) (Levocetirizine) UCB
*CLARINEX(Desloratadine)Schering-Plough (loratadine[CRARITIN]活性体) 1997.12 世界独占販売権をSchering-Ploughにライセンス。 2002.1 Schering-Plough はCLARINEXとして発売。 (5 mg tablets for the treatment of seasonal allergic rhinitis, or SAR, in adults and children twelve years of age and older.) 2002.2 CIU の追加適応FDA承認。 *ALLEGRA(fexofenadine HCl) Sanofi-Aventis 1993.7 Hoechst-Marion-Roussel(後Aventis→現Sanofi-Aventis)にライセンス。 1996.10発売。 ロイヤリティは1999.3.1から受け取り開始、米国分は2002.1から。 しかし2005.9にジェネリック出現。 *XYZAL(Levocetirizine) UCB 1999.6 UCB Farchim SA(現UCB Pharma)に米国・日本を除く全世界。2006.2.23 UCBに米国ライセンス。 cetirizineの異性体。 2001.2ドイツ、2001Q4他のEU発売。 2000.9.22 日本で承認 2006.7 UCBはXyzal(Levocetirizine)をFDA申請。 Levocetirizine is currently marketed by UCB under the brand names XYZAL and XUSAL(TM) in the E.U. for treatment of symptoms of seasonal and perennial allergic rhinitis, persistent allergic rhinitis and CIU in adults and children six years of age and older. Bronchodilators(Long-acting) US Market (2002)$2 billion 診療科別処方箋枚数比 開業医54%、胸部専門医15%、アレルギー専門医11%、小児科6%、 その他14% *2004.10.1 MedPointe, Inc.とのAstelin(azelastine HCl)の共同販売契約を終了。 *2004.3.25 Ross社(Abbottの子会社)との間のXOPENEX(levalbuterol HCl)共同販売契約 の変更。2004.12末に契約終了。 ★2005年度決算メモ ・2006.1.12 FDAがDey,L.P.によるlevalbuterolのジェネリックANDAを受付。 2005.9.7 FDAがBreath LtdによるlevalbuterolのジェネリックANDAを受付。 (Sepracor社は両社に対し特許侵害訴訟提起。 勝訴の場合ANDA申請は却下、 敗訴の場合、判決日もしくはANDA通知受領日から30ヵ月のどちらか早い方迄 承認は保留される。) ・2005.12.13 arformoterol tartrate吸入液のNDA申請をFDAに提出。 同剤は持続性βアゴニストで、COPDの長期維持療法の適応。 ★2006年度決算メモ ・2006.1 ACADIA Pharmaceuticals Incのthe second $10 million purchase を完了。 ・ ★ciclesonide() ・2008.1 Nycomed社から導入。 米国が対象。 製品はALVESCO HFA Inhalation Aerosol(喘息)およびOMNARIS AQ nasal spray(アレルギー性鼻炎) 2008.2 an upfront payment of $150.0 million 、最終的には$280.0 million迄 ★LUNESTA (eszopiclone) (S)-ZOPICLONE; zopiclone(R,S異性体混合)のS-異性体。 1999.10 Sanofi-Aventis前身Rhone-Poulenc Rorer SAにライセンス。 *2004.7.13 eszopicloneに関するAventisとの契約を変更。米国外でもAventis社のデータ を閲覧可能となった。 Original契約は、zopicloneおよび関連物質を米国で開発販売 する権利をAventisから取得。 zopiclone(IMOVANE and AMOBAN)は世界８０か国で販売。 米国特許は2012.1失効 *Acadia社の株式を取得(2004)。 Lunestaの開発と世界販売を行ってもらう。 [2007] ・2007.9 GSKと開発販売契約。 GSKはLUNIVIA名で販売、地域は米・加・メキシコ・日本を除く全世界。 対価は契約金$20.0 million 、ライセンス・マイルストーン$155.0 million ・2007.7 エーザイと契約。地域は日本。 ・2007.7 GSKがEMEAに申請 ・競合 LUNESTAは処方箋の10%未満。 OTC/健康食品との競合。 AMBIEN (zolpidem tartrate)のGEが2007.4 出現。 AMBIEN CR (zolpidem tartrate extended release)のGEが2009.3 出現予想。 [2006] ・2006.6 日本PMDAと治験相談。 2007.1 P1開始。 [2005] ・2004.12 米国で承認。 ★BROVANA (arformoterol tartrate) Inhalation 喘息薬；COPD ・(R,R)-FORMOTEROL ・formoterol(米加FORADIL[Novartis]、日本ATOK[アステラス])の（R,R）-エナンチオマー 同剤は持続性βアゴニストで、COPDの長期維持療法の適応。 ・即効性でかつ長時間作用型の気管支拡張剤で既存薬に優る効果。 １日１回投与の吸入剤。 ・2000年Q4にP2終了。2001.9 P3開始 [2006] ・2006.10 FDA承認。 2007.4発売 15 mcg as a long-term, twice-daily (morning and evening), maintenance treatment of bronchoconstriction in patie nts with chronic obstructive pulmonary disease, or COPD, including chronic bronchitis and emphysema. BROVANA is for use by nebulization only. [2005] ・2005.12.13 arformoterol tartrate吸入液のNDA申請をFDAに提出。 ★levalbuterol tartrate inhalation (Xopenex HFA) ・indicated for the treatment or prevention of bronchospasm CFCを含まない。 ・2005.3 FDA承認、2005.12米国発売。 ★levalbuterol hydrochloride inhalation (Xopenex Inhalation) ・[特許]2010.1-2013.8に失効する５つの特許. 他に米国外特許１件はMarch 2021迄. [2006] ・2006.8 Dey, L.P社がFDAにジェネリック品申請 ・2006.4 Watson Laboratories, IncがFDAにジェネリック品申請 当社特許は2021に失効 [2000] ・1999.5 米国発売 ・1999.11 Abbott Laboratoriesと共同販売契約 ●失敗したプロジェクト(2007) ★(S)-amlodipine P2完了 高血圧 ・Amlodipine(NORVASC[Pfizer])の異性体 [2005] ・P1/2終了し、評価完了。 導出候補品。 ★(R)-FLUOXETINE P3中止 うつ病 ・fluoxetine(PROZAC[Lilly])の異性体。 ・1998.12 Eli Lillyにライセンス。 しかし2000.10.19契約終了。 ・高用量で不整脈(QTc intenual)を誘発すると判明したため2000年開発中止。 ★TICALOPRIDE(旧(+)-norcisapride) P2中止 胸焼け ・cisapride(PROPULSID[Janssen])の活性代謝物の異性体 ・1998.7 Janssen Pharmaceutica, N.Vにライセンス。 ・2003.10 開発中止 ★tecastemizole(旧norastemizole)(SOLTARA(TM)) 申請取下げ アレルギー性鼻炎 ・astemizole関連物質 ・2001.3.12 FDA申請、2002.3.7 FDA非承認レター(安全性データ不足)、2003.12.2開発中止 ・開発中止に伴い2003度にwe incurred a non-cash charge of approximately $19,000,000 in 2003. ★(S)-OXYBUTYNIN P3中止 尿失禁、過活動膀胱 ・oxybutynin(DITROPAN(ALZA))の異性体 ・資金上の理由で2004年臨床試験の継続を保留 ★その他 (2000) 2000年度次のプロジェクトが検討されていたが、2001-2007年度での報告はなく、中止。 (S)-Doxazosin 前立腺肥大 ・doxazosin(CARDURA(Pfizer))の異性体 (S)-Lansoprazole ・Lansoprazole(PREVACID[TAP Pharmaceuticals])の異性体 (-)-Pantoprazole ・pantoprazole(PANTOZOL(Byk-Gulden))の異性体
●Sepracor Inc. ■Products & Pipeline ●Marketed Products Lunesta(TM)(eszopiclone)...睡眠薬 Xopenex HFA(levalbuterol tartrate)...喘息 Xopenex(levalbuterol HCl)...喘息 BROVANA(TM) (arformoterol)...COPD OMNARIS(TM) (ciclesonide)...アレルギー性鼻炎 ●開発中 SEP-0002093(eslicarbazepine acetate) ...申請準備中 (てんかん) *Bial-Portela & Ca, S.Aから導入(2007.12) SEP-225289 ...P2 (うつ病) *a triple reuptake inhibitor SEP-227162 ...P1完了 (うつ病) *a serotonin and norepinephrine reuptake inhibitor (SNRI) SEP-225441 ...P2 (不安症) *an agonist of the alpha receptor of the gamma aminobutyric acid, or GABA, complex ●Therapeutic Area ■Investor Information ●Annual Reports Annual Report 2007[pdf,p] Annual Report 2006[pdf,p] Annual Report 2005[pdf,127p] Annual Report 2004[pdf,74p] Annual Report 2003[pdf,56p] Annual Report 2002[pdf,60p] ★Fact Sheet[pdf,4p]～喘息薬、睡眠剤などの市場規模データ ●SEC Filings 10-K Annual report[2008.2.29] - [pdf] 10-K Annual report[2007.3.1] - [pdf,155p] 10-K Annual report[2006.3.16] - [pdf,161p] 10-K Annual report[2005.3.16] - [pdf] 10-K Annual report[2004.3.15] - [pdf] 10-K Annual report[2003.3.31] - [pdf] 10-K Annual report[2002.4.1] - [pdf] 10-K Annual report[2001.3.28] - [pdf] ★Press Release Sepracor Inc. Reports 2007 Fourth Quarter and Full-Year Results[2008.2.29] Sepracor Announces Fourth Quarter and Full Year 2005 Results; Sepracor Reports
First Profitable Year; 2005 Product Revenues Increase by 116% Over 2004[2006.1.31] Sepracor Announces Fourth Quarter and Full Year 2004 Operating Results[2005.1.27] Sepracor Announces Fourth Quarter and Full Year 2003 Operating Results[2004.1.22]
■Servier[FR]
- http://www.servier.com/ ; 株式非公開 従業員総数20,000 ;世界１４０ヵ国で販売；フランス第二位の製薬会社
●LES LABORATOIRES SERVIER ●Products ●Healthcare Professionals
●日本セルヴィエ株式会社
■Shire Pharmaceuticals Group plc[UK]
- http://www.shire.com/shire/; 本社in Basingstoke, UK. 1986 設立。 当初hormone replacement therapy (HRT) を手がける。 アルツハイマー薬galantamine (Reminyl)をJanssenと共同開発 1996.2 ロンドン株式市場上場。 ６社買収 1997 米国製剤技術会社Pharmavene社を買収。 米国Richwood社を買収。 Adderal(ADHD薬)を入手 1999 Fuisz社およびRoberts Pharmaceutical社を買収。Agrylin and Lodineを入手 2001 カナダBiochem Pharmaを買収。 HIV薬3TCを入手。 2004.9 ワクチン事業をID Biomedical Corporation (IDB)に売却。 2005.7 Transkaryotic Therapies Inc.(TKT) を買収。Replagalを入手。2006.1 Shire Human Genetic Therapies, Inc. (Shire HGT)に社名変更 2007.2 New River Pharmaceuticals Incを買収($2.6 billion)。VYVANSE(TM) (lisdexamfetamine dimesylate)を入手。 2008.10.1 Shire Limited (LSE: SHP, NASDAQ: SHPGY),Dublin, Ireland 社名をShire plcに変更。 Jerini AGを買収。 ●決算●製品売上高
($ milllion) 2008 2007 2006 2005 2004 2003 2002 2001 2000 売上高 3,022.2 2,436.3(+36) 1,796.5(+12) 1,599.3(+17) 1,363.2(+13) 1,211.6(+19) 1,037.3 853.0 647.7 製品売上高 2,754.2 2,170.2(+41) 1,535.8(+16) 1,327.7(+19) 1,112.5(+11) ロイヤリティ 245.5 247.2(+2) 242.9(+0) 242.9 230.4(+13) ライセンス・開発 - - - 15.0 13.5 他の収入 22.5 18.9(+6) 17.8(-38) 28.7
旧13.76.9 営業利益 412.0 (1,379.1)
旧(1,398.1)283.2
旧316.8(524.9)
旧(491.7)
旧(354.1)412.9
旧446.4(+6)419.6 327.0 143.1 140.3 純利益 156.0 (1,451.8) 278.2 -578.4
旧-410.8269.0(-3) 276.1 250.6 38.8 211.7 研究開発費 526.6 576.4
旧566.6[26%]385.4
旧380.5(+14)[25%]339.1 196.3(+5) 187.7 189.2 171.0 取得研究開発費 263.1 1,866.4 - 従業員数 3,769 3,436 2,868
($ milllion) 2008 2007 2006 2005 2004 2003 2002 備考 製品売上高計 2,754.2 2,170.2(+41) 1,535.8(+16) 1,327.7(+19) 1,112.5(+11) 1,029.8(+20) 859.4 ★ADHD ADDERALL XR 1,101.7(+7) 1,030.9(+19) 863.6(+18) 730.8(+20) 606.7(+28) 474.5(+49) 317.9 [mixed amphetamine salts] ADHD [ADHD市場] 25.5 26.1% 26% 25% 23% 18% 米国各12月シェア ADDERALL - - 23.6(-45) 43.1 - 61.1 109.8 [mixed amphetamine salts] ADHD;2006.9権利をDuramedに$63.0 millionで売却 [ADHD市場] - - 2% 5% 米国各12月シェア Dytrana 78.7(+23) 64.2(+156) 25.1(-) - [methylphenidate transdermal system]ADHD;発売2006.6 [ADHD市場] 2.1 0.8% 米国各12月シェア Vyvanse 318.9(+317) 76.5(-) - [lisdexamfetamine dimesylate]ADHD;米発売2007.7 [ADHD市場] 5.2% 米国各12月シェア ★消化器系 Colazide - 9.2(+7) 8.6 [balsalazide disodium]潰瘍性大腸炎 Pentasa 185.5(+5) 176.4(+28) 137.8(+1) 136.1(+18) 115.0(+16) 99.3(+14) 87.2 [mesalamine]潰瘍性大腸炎 [&olsalazine市場] 17.2 17.3% 18% 18% 17% 18% 米国各12月シェア Lialda/Mezavant(2008-) 140.4(+178) 50.5(-) - - [mesalamine]米発売2007.3,英2007.11 [&olsalazine市場] 8.0% 米国各12月シェア ★腎臓 FOSRENOL 155.4(+52) 102.2 44.8(-16) 53.5(-) - - - [lanthanum carbonate]*米発売2005.1/Hyperphosphatemia高リン血症;24ヵ国発売(2007末) [リン酸結合剤] 8.6 8.5% 8% -% -% - 米国各12月シェア Dynepo - 14.2(-) - - [Epoetin-delta]貧血;独発売2007.3;英仏伊2007後半発売;Transkaryotic Therapeutics社品 ★一般 AGRYLIN&XAGRID - 66.8(+25) 53.3
旧60.892.8(-39) 152.5(+15) 132.5(+11) 119.2 [anagrelide]血小板増多症 Agrylin(北米) - - 7.5 46.0(-61) 119.1 - - [anagrelide];2005.4米国GE発売 Xagrid(欧州) 78.7(+18) 66.8(+25) 53.3(+14) 46.8(+40) 33.4 - - [anagrelide]Thrombocythemia CALCICHEW range 52.8(-3) 54.2(+19) 45.5(+18) 38.7 - 28.9(+25) 23.2 [calcium carbonate with or without vitamin D3)]骨粗鬆症 CARBATROL 75.9(+5) 72.3(+6) 68.3(-5) 72.1(+33) 54.3(+4) 52.4(+16) 45.3 [CARBAMAZEPINE]抗てんかん剤 [carbamazepine市場] 42% 42% 46% 43% 36% 米国各12月シェア Reminyl,XL 34.4(+10) 31.2(+45) 21.5(+59) 13.5 [galantamine hydrobromide]アルツハイマー型痴呆症；英国・アイルランド;Synaptech, Inc.が権利保持 他の一般医薬品 50.1(-58) 119.3 PROAMATINE - - - - - 49.3(+3) 50.9 [midodrine]低血圧 [&fludrocortisone市場] - - 15% 25% 米国各12月シェア Solazine - - 13.2(+6) 12.5 [diclofenac sodium (3%w/w))]actinic keratosis(光線角化症) Vaniqa - - 7.9(+25) 6.3 [eflornithine]女性用facial hirsutism(顔面多毛症) Lodine - - 12.6(-) 12.6 [etodolac]鎮痛・抗炎症剤 【医療用医薬品 計】 2,272.5(+23) 1,844.5 ★HGT[Human Genetic Therapies] REPLAGAL 176.1(+22) 143.9(+22) 117.7(-) 41.3(-) - - - [Agalsidase Alfa]*TKT製品;Fabry Disease (2005売上高は5ヵ月分のみ、TKT期間通算$94.6 million(2004:US$77.4 million)) Elaprase 305.1(+68) 181.8(+670) 23.6(-) - [idursulfase]Hunter症候群(Mucopolysaccharidosis II)発売米2006.8 FIRAZYR 0.5 - - - - - - [Icatibant]成人における遺伝性血管浮腫（C-１エステラーゼ阻害欠損を伴う）の急性発作の対症療法;欧Jerini AGが2008.7.11承認 【HGT 計】 481.7(+48) 325.7 ★その他 Others 105.1(-5) 111.0
旧60.6(-8)65.8 183.9(-25) 131.8(+24) 105.9 ●Royalty収入 245.5(-1) 247.2(+2) 242.9 242.9 230.4(+13) 203.6(+16) 174.8 3TC 140.2 145.3(-4) 150.9(-6) 159.8(+3) 155.8(+8) 144.6(+9) 132.5 from GSK (GSK世界売上高) 1,060 1,110 1,138 1,211(+2) 1,184 ZEFFIX 40.3(-2) 41.0(+18) 34.8(+14) 30.5(+11) 27.4(+11) 24.7(+17) 21.2 from GSK (GSK世界売上高) 341 301 266(+11) 240 Others 65.0 60.9(+6) 57.2(+9) 52.6(+11) 47.2(+37) 34.3(+63) 21.1 REMINYL from J&J ●主要製品[2008.6.10]
●[ADHD market 2009 & 2008 & 2007 & 2006] 【2009】ADHD is one of the most common psychiatric disorders in children and adolescents (J Am Acad Child Adolesc Psychiatry,2007). Worldwide prevalence of ADHD is estimated at 5.3 percent (Am J Psych. 2007). In the US, approximately 7.8 percent of all school-aged children, or about 4.4 million children aged 4 to 17 years, have been diagnosed with ADHD at some point in their lives (CDC, 2005). According to the Results from the National Comorbidity Survey Replication (Am J Psychiatry, 2006), the disorder is also estimated to affect 4.4 percent of US adults aged 18 to 44. When this percentage is extrapolated to the full US population aged 18 and over, Shire estimates that approximately 9.8 million adults have ADHD (based on US Census 2000 kｿ 2005). According to IMS, a leading global provider of business intelligence for the pharmaceutical and healthcare industries, the US market for ADHD treatments was valued at approximately $4.7 billion for the year to December 31, 2009, an increase of 10% from the year to December 31, 2008.
Competition in the US ADHD market has increased with the launch of competing products in recent years, including the launch of authorized generic versions of ADDERALL XR by Teva and Impax in 2009. This generization has resulted in a decline in sales of ADDERALL XR and in December 2009 authorized generic versions of ADDERALL XR had a 12% share of the US ADHD market. Shire’s share of the US ADHD market in December 2009 was 25.9% (2008: 32.7%) Shire has four products within the US ADHD market:
kﾎADDERALL XR, an extended release treatment for ADHD designed to provide once daily dosing, launched in 2001;
kﾎDAYTRANA, a methylphenidate transdermal product for the treatment of ADHD, launched in 2006;
kﾎVYVANSE, a stimulant pro-drug product for the treatment of ADHD, launched in 2007; and
kﾎINTUNIV, a non-stimulant, non-scheduled treatment for ADHD, launched in November 2009.Many products which compete with the Company’s ADHD products in the US contain methylphenidate, including the following once-daily formulations: CONCERTA, launched in 2000 by J&J (in conjunction with Alza): METADATE CD, launched in 2001 by UCB; RITALIN LA, which is an extended release formulation of methylphenidate, launched by Novartis (in conjunction with Elan) in 2002; and FOCALIN XR, which is a long-acting formulation of dexmethylphenidate, the active ingredient of traditional methylphenidate preparations, launched by Novartis (in conjunction with Celgene Corporation) in 2005. In December 2009, CONCERTA, METADATE CD, RITALIN LA and FOCALIN XR had a 17.9%, 1.9%, 1.4% and 6.0% share of the US ADHD market, respectively. In 2003, Eli Lilly launched STRATTERA, a nonstimulant, non-scheduled treatment for ADHD. In December 2009, STRATTERA had a 6.3% share of the US ADHD market.
Key competitors in the European ADHD market are CONCERTA (Janssen-Cilag), RITALIN LA (Novartis), and MEDIKINET (Medice) depending upon the country.
The Company is also aware of clinical development efforts by GSK (in collaboration with Neurosearch), Cortex Pharmaceuticals Inc., Eisai Inc., BMS (in collaboration with Otsuka), AstraZeneca (in collaboration with Targacept), CoMentis, Shionogi/Sciele (in collaboration with Addrenex), Eli Lilly, J&J, Pfizer, Merck, Schering-Plough/Organon, PsychoGenics, Supernus and Abbott to develop additional treatment options for ADHD.
【2008】Competition in the US ADHD market has increased as several products that compete with the Company's products have been launched in recent years. The Company has also introduced two new entrants to the market: VYVANSE, the Company's stimulant pro-drug product, launched in 2007 and DAYTRANA, the Company's methylphenidate transdermal product, launched in 2006. Additional competition will result in 2009 from the anticipated launch of generic ADDERALL XR beginning in April 2009, and other ADHD products could face generic competition in the future. Many of the competing products contain methylphenidate. In 2000, Johnson & Johnson (in conjunction with ALZA) launched CONCERTA, a once-daily formulation of methylphenidate. For the month of December 2008, CONCERTA had a 19.4% share of the US ADHD market. In 2001, UCB launched METADATE CD, a once-daily formulation of methylphenidate. In December 2008, METADATE CD had a 2.4% share of the US ADHD market. In 2002, Novartis (in conjunction with Elan) launched RITALIN LA, an extended release formulation of methylphenidate, and in 2005 Novartis launched FOCALIN XR in conjunction with Celgene Corporation (“Celgene”), a long-acting formulation of dexmethylphenidate, the active ingredient of traditional methylphenidate preparations. In December 2008 RITALIN LA and FOCALIN XR had a 1.7% and 6.0% share, respectively, of the US ADHD market.
In 2002, Barr launched a generic version of ADDERALL. Subsequently, five additional companies have launched generic versions. Total ADDERALL generic prescriptions accounted for about 14.7% of the US ADHD market for the month of December 2008. In September 2006, Duramed purchased the product rights to the Company's ADDERALL product for $63 million. For further information see ITEM 7: Management's Discussion and Analysis of Financial Condition and Results of Operations .
In 2003, Eli Lilly launched STRATTERA, a non-stimulant, non-scheduled treatment for ADHD. As of December 2008, STRATTERA had a 7.4% share of the US ADHD market . The Company's non-stimulant product INTUNIV is in registration in the US.
The Company is also aware of clinical development efforts by GlaxoSmithKline (in collaboration with Neurosearch), Cortex Pharmaceuticals Inc., Eisai Inc., BMS (in collaboration with Otsuka), AstraZeneca (in collaboration with Targacept), CoMentis, Shionogi/Sciele (in collaboration with Addrenex), Eli Lilly, Johnson & Johnson, Pfizer, Merck, Schering-Plough/Organon, PsychoGenics, Supernus and Abbott to develop additional indications and new non-stimulant treatment options for ADHD.
●INTUNIV(guanfacine持続性製剤) ADHD治療薬 The FDA approved INTUNIV in September 2009 as a once daily treatment for children and adolescents aged 6 kｿ 17 years. Shire launched INTUNIV in November 2009.
●VYVANSE [lisdexamfetamine dimesylate]ADHD;米発売2007.7 VYVANSE is a new chemical entity for the treatment of ADHD and is the first pro-drug stimulant, where the amino acid l-lysine is linked to damphetamine,which is therapeutically inactive until metabolised in the body. 【2009】VYVANSE is a new chemical entity and is the first pro-drug stimulant for the treatment of ADHD, where the amino acid llysine is linked to d-amphetamine, which is therapeutically inactive until metabolized in the body. VYVANSE for the treatment of ADHD in pediatric patients aged 6 to 12 years was approved in 2007 and is available in the US in six dosage strengths: 20mg, 30mg, 40mg, 50mg, 60mg and 70mg, all indicated for once-daily dosing.
In April 2008 the FDA approved the adult indication for VYVANSE, making it the first and only once-daily pro-drug stimulant approved to treat adults aged over 18 years with ADHD. Shire launched VYVANSE in the US for adults with ADHD in June 2008.
In February 2009 Health Canada approved VYVANSE for the treatment of ADHD in pediatric patients aged 6 to 12 years in Canada. Shire launched VYVANSE in Canada in February 2010.
In May 2009 Shire and GSK commenced working together on the co-promotion of VYVANSE for the treatment of ADHD in adults with the aim of improving recognition and treatment of adult ADHD in the US.
In October 2009 the FDA affirmed its decision to grant new chemical entity exclusivity to VYVANSE and refused to accept an Abbreviated New Drug Application (“ANDA”) submitted by Actavis Elizabeth, LLC in January 2009 for generic lisdexamfetamine dimesylate. VYVANSE has new chemical exclusivity through to February 23, 2012 and is also covered by US patents which remain in effect until June 29, 2023.
Litigation proceedings relating to the VYVANSE are in progress. For further information see ITEM 3: Legal Proceedings and Note 23(d), “Commitments and Contingencies, Legal proceedings” to the consolidated financial statements listed under ITEM 15: Exhibits and Financial Statement Schedules of this Annual Report.
【2008】VYVANSE for the treatment of ADHD in children aged 6 to 17 in the EU is in Phase 3 development and Shire expects to submit the regulatory filing for VYVANSE in Europe in 2010. ●EQUASYM(methylphenidate hydrochloride) ADHD治療薬 ●DAYTRANA [methylphenidate transdermal system]ADHD;発売2006.6 In 2009 and January 2010 Shire voluntarily recalled limited lots of DAYTRANA patches because certain patches did not meet their release liner removal specifications which may have resulted in some patients and caregivers having difficulties removing the liners. The voluntary recall was not due to safety issues. Shire and Noven continue to pursue enhancements to the product and to work closely with the FDA to implement changes that may improve the usability of DAYTRANA. There has been no interruption in the production of DAYTRANA.
On January 9, 2008 the FDA issued a Warning Letter to Noven which related to Noven’s manufacture of DAYTRANA. FDA conducted a follow-up inspection of Noven in January 2009. On May 14, 2009, Noven met with the FDA to discuss the progress and completion of corrective actions. A follow-up FDA inspection is anticipated in 2010 to verify that the items identified in the Warning Letter have been addressed and the site meets Current Good Manufacturing Standards (“GMP”) requirements.
【2008】Regulatory submissions were filed for approval of the product with Health Canada in November 2007 and in the EU via the decentralized procedure, with the Netherlands as the reference member state in December 2007. Reviews are ongoing. ●ADDERALL XR [mixed amphetamine salts] ADHD The FDA approved ADDERALL XR as a once-daily treatment for children aged 6 to 12 with ADHD in October 2001, for adults in August 2004 and for adolescents aged 13 to 17 in July 2005.
Teva Pharmaceutical Industries, Ltd. (“Teva”) and Impax Laboratories, Inc. (“Impax”) commenced commercial shipment of their authorized generic versions of ADDERALL XR in April and October 2009, respectively. Shire receives revenues from the supply of authorized generic ADDERALL XR to Teva and Impax. Shire also receives royalties from Impax’s sales of authorized generic ADDERALL XR and, until October 2009, received royalties from Teva’s sales of authorized generic ADDERALL XR. The launch of authorized generic versions has resulted in a decline in Shire’s product sales of branded ADDERALL XR in 2009. For further information see ITEM 7: Management’s Discussion and Analysis of Financial Condition and Results of Operations.
In October 2005 the Company filed a Citizen Petition with the FDA requesting that the FDA require more rigorous bioequivalence testing or additional clinical testing for generic or follow-on drug products that reference ADDERALL XR before they can be approved. The Company received correspondence from the FDA in April 2006 stating that, due to the complex issues raised, which require extensive review and analysis by the FDA’s officials, a decision cannot yet be reached by the FDA. The FDA has not yet reached a decision on this Citizen Petition and did not provide any guidance as to when that decision may be reached.
Teva and Impax commenced commercial shipment of their authorized generic versions of ADDERALL XR in April 2009 and October 2009, respectively. Shire derives revenues from the supply of authorized generic ADDERALL XR to Teva and Impax. Shire also receives royalties from the sale of authorized generic versions of ADDERALL XR. From April 2009 Shire received royalties from Teva’s sales of authorized generic versions of ADDERALL XR (these royalties ceased in September 2009) and from October 2009 Shire received royalties from Impax’s sales of authorized generic ADDERALL XR.
★Reminyl,XL[galantamine hydrobromide] アルツハイマー病 ★リン酸塩結合剤 Ulcerative Colitis market 潰瘍性大腸炎市場 【2008】Ulcerative colitis is a type of Inflammatory Bowel Disease. The primary treatments for patients with ulcerative colitis are 5-ASA containing formulations. More than 88% of all ulcerative colitis patients receive treatment with 5-ASA. Competition in the oral 5-ASA market has remained relatively constant with the Company's LIALDA/MEZAVANT being the only new branded market entrant for patients with mild to moderate ulcerative colitis since the launch of the mesalamine pro-drug COLAZAL in 2001. Shire defines the 5-ASA competitive set as the non-sulfasalazine, oral mesalamine and mesalamine pro-drug products. The US oral 5-ASA market is led by Proctor and Gamble's ASACOL. In December 2008, ASACOL had a 58.9% share of the oral 5-ASA market, declining from 63.2% in December of 2007. In December 2008 Salix's COLAZAL had a 1.8% market share, while UCB's DIPENTUM had a 0.9% market share.
The EU oral 5-ASA market is somewhat more fragmented. Major competitors in the UK include Proctor and Gamble's ASACOL which had a 45.8% share of the UK oral 5-ASA market and Ferring's PENTASA tablets had an 18.7% market share in November 2008. The German oral 5-ASA market is led by Dr Falk's SALOFALK, with 56.7% market share, followed by Merkle's CLAVERSAL with 20.0% share in November 2008. CLAVERSAL and PENTASA are the leaders in the oral 5-ASA market in Spain with 42.6% and 41.0% market shares respectively in November 2008. PENTASA sachets are the market leader in France with 42.8% market share of the oral 5-ASA market. Norgine's FIV-ASA had a 15.1% share of the French oral 5-ASA market. Overall, Proctor and Gamble's ASACOL had a 22.0 % share of the EU G5 oral 5-ASA market.
Mesalamine and balsalazide products are generally protected by formulation patents only. In December 2007, the FDA denied Salix's Citizen Petition for COLAZAL and Salix subsequently announced the launch of an authorized generic version by Watson Laboratories. This was followed by the introduction of three other generic versions of COLAZAL.
The Company is aware of other 5-ASA formulation development efforts by Salix and Proctor and Gamble and other non-5-ASA biologic treatments in development for Inflammatory Bowel Disease by UCB and Abbott.
【2007】米国の経口5-ASA市場トップはAsacol(P&G)で2007.12で63.2%のシェア(前年68.7%)。 Colazal(Salix)が10.8%、Dipentum(UCB)は1.2%。 欧州5-ASA市場は分断化しており、英国ではAsacol(P&G)が42.4%、Pentasa(Ferring)が17.4%。 ドイツはSALOFALK(Dr.Falk) 59.1%、次いでClaversal(Merkle) 21.9%シェア。 フランスはPentasa(Ferring)が68.7%とトップ、次いでFIV-ASA(Norgine) 12%。 EU５ヵ国全体ではAsacol(P&G)が32&。 Mesalamine and balsalazideは製剤特許で保護されているが、2007.12 FDAはSalixのColazalの市民誓願を否定し、Watson Laboratoriesのジェネリック製剤を認可した。
★LIALDA/MEZAVANT(mesalamine) 潰瘍性大腸炎 【2008】In April 2008, TAP Pharmaceutical Products Inc. (“TAP”) commenced co-promotion of LIALDA in the US in accordance with the co-promotion agreement entered into in March 2008. This agreement adds more than 500 additional sales representatives from TAP which will increase the reach and frequency of sales calls covering an additional 22,000 doctors ★PENTASA(mesalamine) 2006 潰瘍性大腸炎 【2008】In September 2008 the Company filed a Citizen Petition with the FDA requesting that the FDA require more rigorous bioequivalence testing for generic or follow-on drug products that reference PENTASA before they can be approved. To date, there has been no substantive action on this Citizen Petition by the FDA. [2006] PENTASA controlled release capsules are indicated for the induction of remission and for the treatment of patients with mild to moderately active ulcerative colitis. Ulcerative colitis is a serious chronic inflammatory disease of the colon in which part, or all of the large intestine becomes inflamed and often ulcerated. Typically, patients go through periods of relapse and remission and can suffer from diarrhoea, bleeding and abdominal pain. Once diagnosis is confirmed, patients are usually treated for life. The worldwide diagnosed population for ulcerative colitis is expected to reach 1.4 million by 2015. The first line treatment for inflammatory bowel disease is with mesalamine (5- aminosalicylic acid 5-ASA) based products
PENTASA is an ethylcellulose-coated, controlled release capsule formulation designed to release therapeutic quantities of mesalamine throughout the gastrointestinal tract. In the US, PENTASA is available in 250mg and 500mg capsules.
★COLAZIDE(balsalazide disodium) 潰瘍性大腸炎 【2008】 ●AGRYLIN/XAGRID(anagrelide) 原発性血小板血症/本態性血小板増多症(Essential Thrombocythemia:ET) 【2007】Myeloproliferative disorders (“MPDs”慢性骨髄増殖疾患), including essential thrombocythemia (“ET”) and polycythemia vera(真性多血症, 真性赤血球増加症, 真性赤血球増多症), are a group of diseases in which one or more blood cell types are overproduced. In the case of platelets, which are involved in the blood clotting process, excess numbers can result in abnormal blood clot formation giving rise to events such as heart attack and stroke. Excessive platelet production can also lead to the formation of abnormal platelets, which may not be as effective in the clotting process. This can lead to events such as gastrointestinal bleeding.
【2005】US sales were up 13% in the year to December 31, 2004, primarily due to increased prescription volumes (up 6% compared to 2003) and the effect of price increases in April and November 2003. AGRYLIN had a 28% share of the total US AGRYLIN, hydrea and generic hydroxyurea prescription market in December 2004, compared to 27% in December 2003. 【2004】Sales of AGRYLIN for the year to December 31, 2003 were $132.5 million, an increase of 11% compared to the prior year (2002:$119.2 million). The increase was primarily driven by substantial sales growth outside the US market where AGRYLIN was available on a named patient basis. In addition, US prescription volumes were up 7% over the same period.
AGRYLIN had a 27% share of the total US AGRYLIN, Hydrea and generic hydroxyurea prescription market in December 2003(December 2002: 27%).● *Registered trade mark of ML Laboratories. **Each registered trade marks of GlaxoSmithKline.
Shire Product Marketed in
(オリジン)Product Description ADDERALL XR(R)
(mixed salts of a single entity amphetamine)USA & Canada
(Shire)ADDERALL XR is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) and is a once-daily formulation of ADDERALL. AGRYLIN(R)
(anagrelide hydrochloride)USA & Canada
(Shire)AGRYLIN is indicated for the treatment of essential thrombocythaemia, secondary to a myeloproliferative disorder. CALCICHEW(R) Range
(calcium carbonate with or without vitamin D3)UK & Republic of Ireland
(Nycomed Pharma AS)The CALCICHEW range indicated as supplemental sources of calcium and as adjuncts to conventional therapy in the treatment and prevention of osteoporosis CARBATROL(R)
(carbamazepine extended-release capsules)USA
(Shire)CARBATROL is indicated for the treatment of epilepsy ★COLAZIDE
(balsalazide)UK
(Shire)COLAZIDE is marketed for the treatment of Ulcerative Colitis.
ColazideはLaboratorios Almirallの商標DAYTRANA(TM)
(methylphenidate transdermal system)米(欧・加申請)
(Noven Pharmaceuticals, Inc.から全世界)The first and only transdermal medication approved to treat the symptoms of Attention Deficit Hyperactivity Disorder (ADHD). DYNEPOTM *
Epoetin deltaApproved in the European Union � not yet available
(Sanofi Aventis)Dynepo is indicated for the treatment of anaemia in patients with chronic renal failure. It may be used in patients on dialysis and in patients not on dialysis. ELAPRASE(TM)
(idursulfase)European Union USA and Canada, Japan, Mexico
(Shire)Product Description: human enzyme replacement therapy for the treatment of Hunter syndrome, also known as Mucopolysaccharidosis II (MPS II). Hunter syndrome is a rare, life-threatening genetic condition that results from the absence or insufficient levels of the lysosomal enzyme iduronate-2-sulfatase. Without this enzyme, cellular waste products accumulate in tissues and organs, which then begin to malfunction. ★EQUETROTM
(carbamazepine extended-release capsules)USA
()EQUETRO is indicated for the treatment of acute manic and mixed episodes associated with bipolar 1 disorder. Advanced drug delivery technology enables the convenience of twice-daily dosing. FOSRENOL(R)
(lanthanum carbonate)Australia, Austria, Belgium, Canada, Cyprus, Czech Rep, Denmark, Finland, France, Germany, Greece, Iceland, Ireland , Korea, Netherlands, Norway, Sweden, Taiwan, UK and USA
(Shire)FOSRENOL is indicated to reduce serum phosphate in patients with end-stage renal disease. LIALDA(TM)/MEZAVANT(R)
(mesalamine) with MMXTM TechnologyUSA, Canada, UK, Ireland, Germany
(Giuliani SpA)LIALDA indicated for the induction of remission in patients with active, mild to moderate ulcerative colitis (UC), a type of inflammatory bowel disease. LIALDA is the first and only FDA-approved once daily oral formulation of mesalamine. The U.S. Food and Drug Administration (FDA) approved LIALDA on January 16, 2007. PENTASA(R)
(mesalamine)USA
(Ferring A/S)PENTASA is indicated for the induction of remission and treatment of patients with mild to moderately active ulcerative colitis. PROAMATINE(R)
(midodrine hydrochloride)USA
()PROAMATINE is indicated for the treatment of symptomatic orthostatic hypotension. REMINYL(R)XL
(galantamine hydrobromide)UK & Republic of Ireland
(Synaptech, Inc.)REMINYL is indicated for the symptomatic treatment of mild to moderately severe dementia of the Alzheimer type. REPLAGALTM
I mg/ml
(agalsidase alfa)European Union, Australia, Canada, Iceland, Israel, New Zealand, Norway, Romania, Switzerland, Taiwan
(Shire)Replagal is indicated for long-term enzyme replacement therapy in patients with a confirmed diagnosis of Fabry Disease ( α -galactosidase A deficiency). ★SOLARAZETM (3%, gel diclofenac sodium (3%w/w)) UK, Republic of Ireland, Italy, France, Portugal, Sweden, Germany, Norway, Denmark, Finland and Germany
(Jagotec A.G.)SOLARAZE is indicated for the treatment of actinic keratosis. 3TC(R) **
tablets
(lamivudine) EPIVIR(R)**
COMBIVIR(R)**
TRIZIVIR(R)**
World wide
()3TC, also marketed as EPIVIR, in combination with other antiretroviral agents is indicated for the treatment of human immunodeficiency virus (HIV) infection. Lamivudine is a component of the combination HIV treatments, COMBIVIR and TRIZIVIR. ★VANIQA(R)
11.5% cream
(eflornithine)UK, Republic of Ireland, France, Italy, Germany and Spain
(Skinmedica, Inc.)VANIQA is indicated for the treatment of facial hirsutism in women. VYVANSE(TM)
(lisdexamfetamine dimesylate)USA(欧P3,加申請準備)
(Shire)VYVANSE (lisdexamfetamine dimesylate) is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). XAGRID(R)
0.5 mg hard capsule
(anagrelide hydrochloride)UK, Sweden, Denmark, France, Germany, Republic of Ireland, Norway
(Shire)XAGRID (anagrelide hydrochloride) is indicated for the reduction of elevated platelet counts in at-risk essential thrombocythaemia patients who are intolerant to their current therapy or whose elevated platelet counts are not reduced to an acceptable level by their current therapy. ZEFFIX(R)**
(lamivudine)World wide
()ZEFFIX is indicated for the treatment of chronic hepatitis B infection associated with evidence of hepatitis B viral replication and acute liver inflammation.
●Shire Pharmaceuticals Group plc ●Products ●News & Media ★Press Releases -Shire ★Press Releases -Non-Shire ★TKT Archive ★New River Archive ●R&D Pipeline /2007.8.23 ■Investors Relations ●Investor News Excellent results in a transformational year for Shire; core product sales up 25%[2010.2.19] ●SEC Filings 10-K Annual Report[2010.2.26] - [pdf] - [doc] 10-K[2009.2.27] - [pdf,228p] - [doc] 10-K[2008.2.25] - [pdf,206p] - [doc] ●Annual Reports Annual report and accounts for the year ended December 31, 2009 [2010.3.25] Annual Review and Summary Financial Statement 2009 [2010.3.25] 10-K Report Year End 2009 [2010.2.26]
Shire has a total of 14 projects in full development of which 4 are in phase II or beyond.
Indication Project Preclinical Phase
IPhase
IIPhase
IIIRegistration Specialty Pharma ADHD SPD503 ADHD SPD465 Valrocemide for CNS disorders SPD493 Moderate to severe pain SPD491 Platelet-lowering agent SPD535 Extended-cycle oral contraceptive SEASONIQUE(R) Transvaginal ring technology Tissue protective cytokines SPD500 Acute pain NRP290 Hypothyroidism NRP409 Prevention and reduction of scarring(肥厚性瘢痕,ケロイド) JUVISTA(R) Human Genetic Therapies Gaucher disease GA-GCB Hunter syndrome CNS Sanfilippo A syndrome Metachromatic Leukodystrophy
■Transkaryotic Therapies, Inc. (TKT)[US]
- http://www.tktx.com/; 設立July 1988。 バイオベンチャー、NASDAQ:TKTX 本社Cambridge, Massachusetts, USA。 子会社Sweden。 従業員数300(2003年末) ●2005.7 Shire Pharmaceuticals Group plc[UK]が Transkaryotic Therapies Inc.(TKT) を買収。Replagalを入手。2006.1 Shire Human Genetic Therapies, Inc. (Shire HGT)に社名変更 ●売上 ($000) 2003 2002 2001
Replagal 57,225 34,682 3,535 (agalsidase alfa)ファブリー病
製品売上 $57,225 $34,682 3,535 License収入 1,664 1,818 2,653 収入合計 58,889 36,500 6,188
純損失 75,234 129,762 70,243
●Transkaryotic Therapies, Inc. (TKT) ●製品 Replagal ●疾病 Fabry Disease ●Investor Information Press Releases Annual Report ●Press Release
■SkyePharma PLC[英]
- http://www.skyepharma.com/ ; 英国。 １４ヵ国に従業員140名。 1996年設立 製剤技術とくに吸入剤に優れたメーカー。 経口剤 Geomatrix ●会社決算●個別製品
(￡ milllion) 2007 2006 2005 2004 2003 2002 2001 収入(継続事業) 41.6 43.0 収入(中止事業) 売上原価 16.1 18.0 粗利益 25.5 25.0 営業利益 (15.7) (28.3) 経常利益 (23.7) (19.3) 当期純利益(継続事業) (24.0) (20.1) 当期純利益(中止事業) (3.0) (59.0) 研究開発費 25.2 22.9 従業員数[連結]
Solaraze(R) [2007]
Solaraze(R) (diclofenac), a topical gel treatment of actinic keratosis, is marketed in the US by Doak Dermatologics, a subsidiary of Bradley Pharmaceuticals, Inc. (“Bradley”), which was acquired by the Nycomed Group (“Nycomed”) in February 2008. Sales in 2007 were approximately US$31 million (￡15.5 million), up by approximately 40% on 2006.
The acquisition of Bradley has added further branded dermatologics to the PharmaDerm division of Nycomed US Inc (“Nycomed US”) and will provide an enhanced platform for in-licensing and co-promotion of dermatology products. Nycomed plans to leverage its manufacturing and distribution capabilities to support the Bradley product lines, improve customer service and optimise the cost structure. In addition, Nycomed US will leverage the combined sales and marketing capabilities to enhance both the Bradley and Nycomed product lines. SkyePharma's low teens royalty on net sales is unaffected by the acquisition.
2007 sales in Europe and certain other territories by Shire PLC (“Shire”) were US$15.5 million (￡7.8 million), compared with the US$13.2 million (￡6.6 million) reported in 2006. In October 2007 it was announced that the distribution and marketing rights for Solaraze(R) were being divested by Shire to Laboratorios Almirall, S.A. (“Almirall”) together with a portfolio of other products and this transaction has now been completed. In the third quarter of 2007, the product was launched in Australia by CSL Biotherapies under an agreement with Shire (now taken over by Almirall). SkyePharma's low teens royalty on relevant net sales is not affected by the transfer from Shire to Almirall in respect of which the Group has received a small consent fee.
●SkyePharma PLC - http://www.skyepharma.com/ ■Products ●Approved Products
●Pipeline Products
LICENSEE/PARTNER PRODUCT NAME GENERIC NAME PRIMARY INDICATION MARKETED ORAL GlaxoSmithKline Paxil CR™ paroxetine Depression Requip® XL 24-Hour™ ropinirole Parkinson’s disease sanofi-aventis Xatral® OD/ Uroxatral® alfuzosin BPH (urinary symptoms) Sciele Pharma Triglide® fenofibrate Lipid disorders Sular® Geomatrix™ nisoldipine Hypertension Roche Madopar DR® levodopa + benserazide Parkinson’s disease Critical Therapeutics ZYFLO CR™ zileuton Asthma Therabel Coruno® molsidomine Angina Ratiopharm diclofenac-ratiopharm® uno diclofenac Pain/inflammation INHALATION AstraZeneca Pulmicort® HFA-MDI budesonide Asthma Novartis Foradil® Certihaler® formoterol Asthma TOPICAL Nycomed/Almirall Solaraze® diclofenac Actinic keratosis ■Investors ●Financial Information Annual Report 2007 ●Press Releases SkyePharma PLC Solaraze(R) Receives Approval in Australia[2006.11.28] ------------------ Skyepharma Announces Bioglan As U.S. Marketing Partner For Solaraze[2001.1.4] - 英SkyePharma PLC社の発表によると、同社はSolarazeの販売権を英Bioglan Pharma PLC にライセンス。 対象地域はU.S., Canada and Mexico。 2000.3に既に欧州(英仏独伊, Swede)の製造販売権をライセンス済みで申請中であり、2001年前半承認見込み。 SolarazeTM - 3% diclofenac in 2.5% hyaluronan gel SkyePharma Withdraws Bioglan Termination Notice for Solaraze[2001.12.21] - 英SkyePharma PLC社は2001.11.20、Bioglan Pharma PLC とのSolaraze契約を終了する。 Bradley Pharmaceuticals to Acquire Bioglan Pharmaceuticals From Quintiles Transnational[2004.6.9] - 関連記事 - 譲渡価額は現金US$183 million ＋在庫コスト。Quintilesは2002.3 Bioglanを買収した。 FDA Approves Solaraze (Diclofenac Sodium) Topical Gel For Actinic Keratosis[2000.10.23] - 既に欧州(英仏独伊, Swede)で承認済み。 Solaraze (Diclofenac Sodium) Gel, For Treatment Of Actinic Keratosis, To Be Available In US In January 2002[2001.12.10] - Nycomed US Inc. Acquires Bradley Pharmaceuticals, Inc.[2008.2.21] - [] -
LICENSEE/
PARTNERPRODUCT ACTIVE PRIMARY
INDICATIONPRE-CLINICAL PH I PH II PH III FILED ORAL Nitec Lodotra™ prednisone Rheumatoid
arthritisAvailable SKP-1032 undisclosed Pain/
inflammationSomnus SKP-1041 undisclosed Sleep
disordersINHALATION Abbott US Flutiform™ formoterol
fluticasoneAsthma Mundipharma
EuropeFlutiform™ formoterol
fluticasoneAsthma Kyorin
JapanFlutiform™ formoterol
fluticasoneAsthma PRE-CLINICAL Dr. Reddy's
LaboratoriesSKP-2045 undisclosed undisclosed
■Smith & Nephew plc[UK]
- http://www.smith-nephew.com/ 設立1856年。 年間売上￡1.2 billion、従業員数7000人以上、３２か国で事業。 ３つの事業分野：整形外科、内視鏡[Endoscopy]、創傷管理。 傷テープから事業展開してきた。 ●損益 (￡million) 2003 2002 2001 2000 1999 売上 1,178.9 1,109.9 1,081.7 1,134.7 1,119.9
整形外科製品 525.4(+16) 470.2 404.6 内視鏡 300.0(+4) 291.8 252.8 創傷管理製品 353.5(9) 321.7 285.6
経常利益 230.1 177.9 193.6 265.2 182.1 純利益 242.2 209.9 180.9 178.9 172.7 * 個別製品売上は明示されない[年報・20-F共]。
●Smith & Nephew plc[UK] - http://www.smith-nephew.com/ ●Investor Relations Annual REports & Results Product Portfolio -製品 - [創傷管理]Collagenase - [整形外科]Supartz[ヒアルロン酸] ●News - 事業別、自由に指定検索、いずれも対応。[1997～] - Strong Performance in Orthopaedics Leads Growth at Smith & Nephew[2004.2.5] ●Innovations ●What We Do
■Solvay S.A.
- http://www.solvay.com/ 1999.7 Unimed Pharmaceuticals, Inc 100%買収 2005.1.19 Neopharma AG[スエーデン] 100%買収 2005.7.28 Fournier Pharma 100%買収 【米アボット】ソルベイの製薬部門買収‐新興国市場のインフラ獲得へ[2009.9.30] 【データモニター】ソルベイ買収でアボットの成長率は大幅改善[2009.10.9] ●会社決算「財務分析」用語一覧 日本で使用しない項目 # EBITDA（Earnings Before Interest Taxes Depreciation and Amortization） 利払い前・税引き前・減価償却前・その他償却前利益 # EBIT（Earnings Before Interest and Taxes）利払い前の税引前当期利益 ●売上
(Euro milllion) 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 グループ売上高 8,485(-11) 9,490(-1) 9,572(+2) 9,399(+10) 8,562(+18) 7,877(+4) 7,557(-5)
旧8,101(-5)7,919
旧8,514医薬品 2,791(+3)[67%] 2,699(+4) 2,591(+0) 2,601(+15) 2,270(+30)[26%] 1,745(-5)[%] 1,832(-2) 1,863(+5) 1,769 1,548 Chemicals 2,713(-12)[25%] 3,096(+2) 3,031(+1) 2,998(+8) 2,785(+14)[33%] 2,692
旧2,433(+2)2,386
旧2,739(-4)2,636
旧2,851Plastics 2,982(-19)[8%] 3,695(-6) 3,950(+4) 3,800(+8) 3,507(+13)[41%] 3,632(+13) 3,215
旧2,105(-9)3,416
旧2,309Plastic 2,198(+22) 1,802 Processing 1,434(+1) 1,423(-4) 1,487 中止事業 491 67(-46) 125 REBITDA 1,375 1,436 1,662 1,568(+13) 1,338 1,146 1,101 1,284 REBIT[対売上%] 905[11%] 965(-19)[10%] 1,192[12%] 1,099[12%] 912[11%] 741[10%]
旧789(+17)673[9%] 844[11%] 医薬品 649(+27) 509(+11) 457(+1) 451(+49) 302 236(-3) 243 263 化学品 246(+3) 238(-31) 345(+9) 315(+11) 285 180(-1) 182 259 Plastic 73(-72) 264(-40) 441(+8) 409(+5) 389 397(+76) 225 327 Plastic 330(+113) 155 Processing 67(-4) 70 Non-Allocated -64 -49 -41 中止事業 22 25(-60) 63 EBIT 800 985(-19) 1,223 経常利益 643 592(-49+) 1,165 当期純利益 553 449(-46) 828 817 816 541 430(-13) 494 403 433 研究開発費 555 564 556 563 472 408 404 399 医薬品 416 428 415 424(+21) 351 294 284 269 人件費 1,981 2,081 2,136
旧2,0521,920 1,698 1,802 1,833 従業員数[連結] 28,204 29,433 28,340 29,258 28,730 26,926 30,139 30,302 31,413 32,294 医薬品 9,188 9,660 9,178 10,088 10,004 化学品 8,721 8,966 8,396 8,691 8,721 プラスチック 8,402 8,816 8,977 8,889 8,474 管理部門 1,893 1,991 1,789 ●開発品目 * 2001 Annual Report ★ホルモン療法 Estrogel 米 申請 HRT Presomen(estrogen/progesteron patch) 欧 P3 Vasomotor symptoms & osteoporosis prevention 米 P3 Vasomotor symptoms ★消化器 KC11458 ,SLV305 P2 Gastric motolity cilansetron P3 IBS Creon P3 Pancreatic insufficiency(日本) ★精神 fluvoxamine-CR P3 Compulsive obsession /Social phobiaの単回投与 DU125530 P2 Depression DU127090 P2 Psychosis/Parkinson's (Lundbeck共同) SLV 308 P2 Parkinson's , Panic and Depression ★循環器 Teveten+HCTZ 米 承認 tedisamil P3 不整脈 moroxonidine+HCTZ P3欧 高血圧 SLV306 P2 高血圧、うっ血性心不全
(Euro milllion) Market 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 ★Men's & Women's Health 648(+3) 627
旧599599(+11) 542[23%] [34%] 682(-4) 713(+10) 646 ? Estratest USA - - 75(-18)[3%] 91(-9)[4%] 100(-24)[6%] 131(-37) 207(+4) 199(+38) 145(+17) [estro-testosterone] Prometrium USA 103(+25) 82(+3) 80(+5) 76(+7)[3%] 71(+20)[3%] 59(-23)[3%] 77(+8) 71(+9) 66(+36) 49(+93) [progestogens];from Schering Corp Femoston Europe+ - - - - - ? ? 27(+43) 16(+20) [estro-progesterone] Duphaston Europe+ 104(+8) 96(+7) 90(+22) 74(+19)[3%] 62(+6)[3%] 59(+2)[3%] -- -- -- 56(+7) [dehydrogesterone] ★(Men's Health) Androgel Global 452(+34) 337(+9) 308(+12) 275(+15)[11%] 239(+3)[11%] 231(-8)[13%] 250(+28) 196(+51) 129(x4) 29(-) [testosterone] ★(消化酵素) 217(+9) 198(+4) 191(+18)[7%] 162[7%] Creon Global 268(+23) 217(+9) 198(+4) 191(+18)[7%] 162(+25)[7%] 130(-5)[7%] 137(-2) 140(+7) 131(+11) 119(+6) [pancrelipase]膵外分泌機能不全 ★(ワクチン) 137(-14) 159(+7) 148(+17) 128[6%] Influvac Europe+ 162(+41) 116(-9) 127(+8) 118(+18)[5%] 100(+32)[4%] 76(+12)[4%] 68(+13) 60(+6) 56(+11) 51(+21) [flu-vac;インフルエンザ] ★消化器 243(+4) 233(-21) 294(-27) 401[18%] [30%] 536(-) 539(+7) 507 Pantoloc Canada - - - 70(-58)[3%] 166(+19)[7%] 139(+12)[8%] 124(+19) 104(+24) 84(+55) 54(+101) [pantoprazole ; from Altana]2006年末で販売契約切れ Duspatal Europe+ 67(+7) 63(+7) 59(+2)[2%] 58(+15)[3%] 55(-2)[3%] 62(+3) 60(+1) 59(+2) - [mebeverine]; IBS Duphalac Europe+ 104(+0) 104(+6) 99(+16) 85(+0)[3%] 85(+9)[4%] 78(+3)[4%] 76(-8) 83 -- 81(0) [lactulose]; 肝性昏睡、便秘 Rowasa USA/仏 - - - - - ? 57(+4) 55(+17) 47(+8) [Mesalamine]大腸炎 Dicetel Europe+ 34(-6) 36 - - 44(+7)[3%] ? ? 41(+22) 34(+9) [pinaverine];大腸炎 ★循環器[Cardiometabolics] 812(+12) 728(+6) 686(+58) 434[19%] [12%] 208(+14) 183(+21) 150 Physiotens Europe+ - 47(-3) 49(-2) 50(-4)[2%] 52(-11)[2%] 58(-3)[3%] 60(+15) 52(+14) 46(+18) 39(+26) [moxonidine] ;高血圧 Teveten Global 110(-5) 116(+9) 106(+12) 95(+4)[4%] 91(+26)[4%] 72(+6)[4%] 60(+25) 53(+49) 35(+127) 16(+20) [eprosartan] ;高血圧[AII] TriCor/Lipanthyl Global 453(-11) 511(+18) 433(+5) 413(+123)[16%] 185(-)[8%] [fenofibrate]発売2004.7;Fournier製品 Aceon USA - - - - - - 28(-3) 29(+39) 21(x7) -- [perindopril];高血圧[ACEI] from Servier ★(NeuroScience)
旧Mental Health411(-6) 439(+2) 430(+14) 376[16%] [18%] 316(-) 318(-11) 356 Serc Europe+ 143(-13) 165(+10) 150(+3) 146(+20)[6%] 122(+27)[5%] 96(+12)[6%] 86(+8) 80(+4) 77(+6) 72(+2) [betahistine]; めまい Luvox/Depromel Japan+ 89(+7) 83(+2) 81(+1)[3%] 80(+4)[4%] 77(-4)[4%] 80(-17) 96(-35) 147(-45) 271(+19) [fluvoxamine]; SSRIうつ病 Marinol USA 47(-56) 105(-1) 106(+26)[4%] 84(+33)[4%] 63(-10)[4%] 70(+32) 53 65(x3) -- [dronabinol];食欲増進剤・嘔吐抑制剤 ★その他 181
●Solvay S.A. ●Sitemap ●Presse -http://www.solvaypress.com/ - 2008 Results[2009.2.19] - 2007 Results[2008.2.15] - New records for Solvay in 2005, after excellent results in 2004[2006.2.16] - Final 2003 results[2004.3.26] - Solvay Group preliminary 2003 results[2004.2.13] - February 11, 2003 SOLVAY GROUP HAS EXCELLENT YEAR IN 2002[2003.2.11] - Preliminary 2002 results[pdf,32p] ●Products -Pharmaceuticals ●Investors ★Annual Reports Annual Report 2008[pdf,166p] Annual Report 2007[pdf,162p] Annual Report 2006[pdf,150p] Annual Report 2005[pdf,116p] ★Library～過去の年報など
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●Unimed Pharmaceuticals, Inc. - 1999.7 Solvay Pharmaceuticals, IncがUnimed Pharmaceuticals, Inc 100%買収 ●Products ★AndroGel(R) (testosterone gel) 1% CIII 男性ホルモン ★ANADROL(R)-50 (oxymetholone) Tablets CIII 蛋白同化ホルモン ★MARINOL(R) (dronabinol) capsules CIII 嘔吐抑制剤 ●News
■Somaxon Pharmaceuticals Inc[US]
- http://www.somaxon.com/ ; NASDAQ symbol “SOMX”. 2003.8 創立Delawareにて ●会社決算Silenor for Insomnia
($ 000) 2009 2008 2007 2006 2005 ライセンス支払 (999) 165 490 1,165 482 研究開発費 4,337 16,546 12,694 37,462 28,955 営業管理費 10,874 18,809 15,614 11,744 4,814 その他経費 - - - - 5,649 営業経費 計 14,212 35,520 28,798 50,371 39,900 営業利益 (14,212) (35,520) (28,798) (50,371) (39,900) 当期純利益 (14,443) (37,227) (26,411) (46,410) (38,487) 従業員数[連結] 5 It is estimated that approximately one-third, or 70 million, of adult Americans are affected by insomnia. One study has found that approximately 20% of those who suffer from insomnia are treated with prescription medications. Silenor was approved by the FDA for the treatment of insomnia characterized by difficulty with sleep maintenance in March 2010. We believe that Silenor has the potential to offer significant benefits to patients with insomnia.
We in-licensed the patents and the development and commercial rights to Silenor and we are preparing for the commercial launch of this product in the U.S. market. Silenor is an oral tablet formulation of doxepin at strengths of 3 mg and 6 mg. Doxepin has been marketed and used for over 35 years at dosages from 75 mg to 300 mg per day and is indicated for the treatment of depression and anxiety. Doxepin has a well-established safety profile, but it has a range of pharmacologic effects at high doses that were not observed in our clinical development program. Our clinical development program for Silenor included four Phase 3 clinical trials, and the primary efficacy endpoint achieved statistical significance in each trial. Our clinical trials for Silenor also demonstrated a favorable safety and tolerability profile, including a low dropout rate, an adverse event profile comparable to placebo, no clinically meaningful next-day residual effects and no evidence of amnesia, complex sleep behaviors, hallucinations, tolerance or withdrawal effects.
Silenor binds to H 1 receptors in the brain and blocks histamine, which is believed to play an important role in the regulation of sleep. The leading approved insomnia medications, Ambien, Sonata and Lunesta, work by binding and activating a different set of brain receptors known as gamma aminobutyric acid, or GABA, receptors. Currently approved GABA receptor-activating drugs are designated by the Drug Enforcement Administration, or DEA, as Schedule IV controlled substances, which require additional registration and administrative controls.
Disease Background and Market Opportunity
Sleep is essential for human performance, general health and well-being. Insomnia, the most common sleep complaint across all stages of adulthood, is a condition characterized by difficulty falling asleep, waking frequently during the night or too early, or waking up feeling unrefreshed. It is estimated that approximately one-third, or 70 million, of adult Americans are affected by insomnia. One study has found that only approximately 20% of those who suffer from insomnia are currently treated with prescription medications. Chronic insomnia, insomnia lasting more than four weeks, is often associated with a wide range of adverse conditions, including mood disturbances, difficulties with concentration and memory, and certain cardiovascular, pulmonary and gastrointestinal disorders. Chronic sleep deprivation has also been associated with an increased risk of depression, diabetes and obesity, among other disorders. The National Institutes of Health 2005 State-of-the-Science Conference statement on the treatment of insomnia stated that estimates placed the direct and indirect annual costs of chronic insomnia at tens of billions of dollars, but cautioned that such estimates were based on many assumptions and varied extensively.
The U.S. market for prescription products to treat insomnia grew to approximately 67 million prescriptions in 2009 according to IMS Health, a growth rate of 5% for the year. According to IMS Health, the insomnia market accounted for more than $2 billion in sales in 2009.
The current market-leading prescription products for the treatment of insomnia include GABA-receptor agonists such as Ambien, zolpidem, the generic form of Ambien, in various formulations, Ambien CR, a controlled-release formulation of Ambien, Lunesta, Sonata and zaleplon, the generic form of Sonata, in various formulations, melatonin agonists such as Rozerem, several hypnotic benzodiazepines such as temazapam (Restoril) and flurazepam (Dalmane), and sedating antidepressants such as trazodone (Desyrel).
According to physicians that we surveyed in our market research, one of the primary reasons they prescribe sedating antidepressants for the treatment of insomnia is that they generally are not associated with the risk of dependency. As a result, they are not Schedule IV controlled substances, and they may be administered for long periods of time. As an example, it is estimated that the majority of trazodone prescriptions are prescribed off-label for the treatment of insomnia.
In our market research, physicians indicated that they would prefer to prescribe sleep medications for their patients that provided a full seven to eight hours of sleep, that removed any risk of dependency and that minimized known side effects of many of the currently prescribed products such as memory impairment, hallucinations and complex sleep behaviors. Our Phase 3 clinical trial program for Silenor demonstrated that patients slept seven to eight hours with no evidence of dependence, tolerance, withdrawal, memory impairment, hallucinations or complex sleep behaviors. When presented with this product profile, the surveyed physicians indicated that Silenor could become the most widely prescribed insomnia product in their practice.
We believe that the introduction of new prescription treatments having different clinical profiles from currently marketed products, coupled with the increased awareness at both the patient and physician levels that chronic sleep deprivation can lead to deleterious health consequences, will translate into an increase in the treatment of insomnia and resultant prescription market growth.
Limitations of Current Therapies
According to a recent Sleep in America Poll, 65% of respondents reported experiencing insomnia symptoms a few nights a week. In addition, 71% of respondents often experienced awakenings during the night or waking up too early without being able to go back to sleep (sleep maintenance), and 26% had difficulty falling asleep (sleep onset). Historically, insomnia therapies have addressed sleep onset rather than sleep maintenance and duration. Only recently have therapies been approved with indications for sleep maintenance, although the ability of available drugs to maintain sleep throughout the night without unwanted next-day residual effects remains limited.
While there are a number of products currently available for the treatment of insomnia, we believe that the market is still underserved due in part to the limitations of current therapies. Our market research indicates that only 25% of patients being treated for insomnia with prescription medications claimed they were very satisfied with their current treatment. The high level of dissatisfaction is frequently attributed to characteristics associated with many of the currently marketed products. For example, 41% of patients claimed that their medication did not provide them with a full night’s sleep, almost one-third of patients claimed they woke feeling groggy, and 33% claimed to have suffered from memory impairment at some time after taking medication, with almost 80% reporting that they found memory lapse somewhat or very scary. Additionally, 24% of patients on prescription insomnia medication claimed that they were dependent on their medication and could not sleep without it.
Technology In-Licenses
In a license agreement entered into in August 2003, as amended in October 2003 and September 2006, we acquired the exclusive, worldwide license from ProCom One, Inc., or ProCom, to certain patents to develop and commercialize low dosages of doxepin for the treatment of insomnia. Although our license to the low-dose doxepin patents is a worldwide license, we currently intend to develop and commercialize Silenor in the United States only, since patent protection for the current dosage form is limited to the United States. The term of the license extends until the last licensed patent expires, which is expected to occur no earlier than 2020. The license agreement is terminable at any time by us with 30 days notice if we believe that the use of the product poses an unacceptable safety risk or if it fails to achieve a satisfactory level of efficacy. Either party may terminate the agreement with 30 days notice if the other party commits a material breach of its obligations and fails to remedy the breach within 90 days, or upon the filing of bankruptcy, reorganization, liquidation, or receivership proceedings relating to the other party.
As consideration for the license, we paid $0.1 million as an option payment and $0.4 million as the first milestone payment for a total of $0.5 million for the period ended December 31, 2003. We paid $0.5 million in January 2005 and an additional $0.5 million in December 2006 in connection with the achievement of milestones. The approval of the Silenor NDA by the FDA in March 2010 triggered an additional $1.0 million payment obligation to ProCom. We are also obligated to pay a royalty on worldwide net sales of the licensed products. We have the right to grant sublicenses to third parties. We also issued 84,000 shares of common stock to ProCom One contemporaneously with our Series A preferred stock financing.
In October 2006, we entered into a supply agreement pertaining to a certain ingredient used in our formulation for Silenor. In August 2008, we amended our supply agreement to provide us with the exclusive right to use this ingredient in combination with doxepin. As part of the amendment, we made an upfront license payment of $0.2 million and are obligated to pay a royalty on worldwide net sales of Silenor beginning as of the expiration of the statutory exclusivity period for Silenor in each country in which Silenor is marketed. Such royalty is only payable if one or more patents under the license agreement continue to be valid in each such country and a patent relating to our formulation for Silenor has not issued in such country. Intellectual Property
We are the exclusive licensee of four U.S. patents from ProCom claiming the use of low dosages of doxepin and other antidepressants. U.S. Patent No. 6,211,229, “Treatment of Transient and Short Term Insomnia,” covers dosages of doxepin from 0.5 mg to 20 mg for use in the treatment of transient insomnia and expires in February 2020.
U.S. Patent No. 5,502,047, “Treatment for Insomnia,” claims the treatment of chronic insomnia using doxepin and expires in March 2013. Due to some prior art that we identified, we initiated a reexamination of our “Treatment for Insomnia” patent.
Silenor Competition
The FDA-approved products that are currently available for the treatment of insomnia consist of sedative hypnotics, including GABA-receptor agonists, hypnotic benzodiazepines and a melatonin agonist. In addition, products such as sedating antidepressants and other products which are not approved for the treatment of insomnia are sometimes prescribed for such use.
Ambien, a GABA-receptor agonist, and its generic equivalents have historically been the market share leaders in the insomnia segment. Generic versions of Ambien (zolpidem) entered the market in April 2007. According to data obtained from IMS Health, generic versions of Ambien accounted for approximately 52% of insomnia prescriptions in 2009. In September 2005, Sanofi-SynthAmlabo, Inc. launched Ambien CR, a controlled-release version of Ambien. Unlike Ambien, Ambien CR is indicated for the treatment of sleep maintenance insomnia and does not have a label restriction limiting the length of time of its use. Ambien CR accounted for approximately 10% of insomnia prescriptions in 2009 and branded Ambien accounted for approximately 1% of insomnia prescriptions in 2009 according to data obtained from IMS Health.
Lunesta, marketed by Sepracor Inc., a wholly-owned subsidiary of Dainippon Sumitomo Pharma Co., Ltd., is a GABA-receptor agonist that was approved in December 2004 by the FDA and was launched in the second quarter of 2005. Lunesta accounted for approximately 8% of insomnia prescriptions in 2009 according to data obtained from IMS Health. Lunesta is indicated for the treatment of insomnia and has been shown to decrease sleep latency and increase sleep maintenance. It was the first of several products to have the short-term use restriction removed from its label.
Sonata, a GABA-receptor agonist marketed by King Pharmaceuticals for the treatment of insomnia, and its generic equivalents accounted for less than 1% of insomnia prescriptions in 2009 according to data obtained from IMS Health.
Rozerem was launched by Takeda Pharmaceuticals North America, Inc. in September 2005 and accounted for approximately 1% of insomnia prescriptions in 2009 according to data obtained from IMS Health. Rozerem is indicated for the treatment of insomnia characterized by difficulty with sleep onset. It was the first drug approved for the treatment of insomnia that is not a Schedule IV controlled substance. With the exception of Rozerem, the approved medications for the treatment of insomnia all act on GABA receptors and are designated as Schedule IV controlled substances. Takeda Pharmaceuticals North America, Inc. conducted a clinical trial to evaluate the administration of a combination of Takeda’s product Rozerem and 3 mg of doxepin in patients with insomnia. We are unaware of the results of this trial.
A number of companies are marketing reformulated versions of previously approved GABA-receptor agonists. In March 2009, Meda AB and Orexo AB received approval from the FDA for Edluar, formerly known as Sublinox, a sublingual tablet formulation of zopidem, for the short-term treatment of insomnia. Meda and Orexo launched this product in the U.S. in the third quarter of 2009.
In December 2008, NovaDel Pharma, Inc. received approval from the FDA for ZolpiMist, an oral mist formulation of zolpidem for the short-term treatment of insomnia characterized by difficulties with sleep initiation. In November 2009, NovaDel and ECR Pharmaceuticals Company, Inc., a wholly owned subsidiary of Hi-Tech Pharmacal Co., Inc., entered into an exclusive license and distribution agreement to commercialize and manufacture ZolpiMist in the United States and Canada. ECR Pharmaceuticals announced that it plans to launch the product in the United States in the first half of 2010.
The remaining market is comprised of older generic benzodiazepines and sedative antidepressants. In addition to the currently approved or off-label products for the treatment of insomnia, a number of new products are expected to enter the insomnia market over the next several years. While the new entrants bring additional competition to the insomnia market, they are also expected to increase the awareness of insomnia and further expand the market. Additionally, we believe market growth will also be driven by the aging of the population and emerging awareness of the links between sleep, health and overall well-being.
Transcept Pharmaceuticals, Inc. submitted an NDA for Intermezzo, a low-dose sublingual tablet formulation of zolpidem, in 2008, and in October 2009, Transcept announced that it received a complete response letter from the FDA relating to such NDA. Transcept held a meeting with the FDA in January 2010 to discuss the implications of the complete response letter, and we do not know the impact that the complete response letter or this meeting will have on the potential approval of this product candidate. Transcept and Purdue Pharmaceutical Products L.P. have entered into an exclusive license and collaboration agreement to commercialize Intermezzo in the United States.
Alexza Pharmaceuticals, Inc. has announced positive results from a Phase 1 clinical trial of an inhaled formulation of zaleplon, the active pharmaceutical ingredient in Sonata. Somnus Therapeutics, Inc. has announced positive results from a Phase 1 clinical trial of a delayed-release formulation of zaleplon. Sanofi-Aventis has completed Phase 3 clinical trials for Ciltyri (eplivanserin), a 5HT2 antagonist, and submitted an NDA for this product to the FDA and The European Agency for the Evaluation of Medicinal Products, or EMEA, for the treatment of insomnia during the fourth quarter of 2008. In September 2009, Sanofi-Aventis announced that it received a complete response letter from the FDA relating to such NDA, and in December 2009 Sanofi-Aventis announced that it was discontinuing the eplivanserin development program.
Vanda Pharmaceuticals Inc. has completed two Phase 3 insomnia clinical trials of VEC-162, a melatonin receptor agonist. Vanda has announced that it intends to submit a marketing application for this product candidate in the United States in mid-2011.
Merck & Co., Inc. has completed two Phase 3 clinical trials of esmirtazapine, an H1 antagonist, for the treatment of insomnia. In February 2010, Merck announced that it was terminating its development program for esmirtazapine for strategic reasons. Merck also has MK-4305, an orexin antagonist, in Phase 3 clinical trials for the treatment of insomnia.
In addition, Actelion Pharmaceuticals Ltd. completed a Phase 3 clinical trial of almorexant, an orexin antagonist, in December 2009 for the treatment of insomnia. Based on the results of that clinical trial, Actelion announced that it was preparing further late-stage trials in adults and elderly patients to evaluate the long-term efficacy and safety of this product candidate. Actelion and GlaxoSmithKline announced a collaboration relating to almorexant under which GlaxoSmithKline received exclusive, worldwide rights to co-develop and co-commercialize almorexant together with Actelion.
Several other companies, including Sepracor, are evaluating 5HT2 antagonists as potential hypnotics, and Eli Lilly and Company is evaluating a potential hypnotic that is a dual histamine/5HT2 antagonist. Additionally, several companies are evaluating new formulations of existing compounds and other compounds for the treatment of insomnia.
●Somaxon Pharmaceuticals Inc ●Silenor(doxepin) ■Investor Relations ●SEC Filings 10-K annual report [2010.3.19] ●News Somaxon Announces FDA Approval of Silenor for the Treatment of Insomnia[2010.3.18]
■Somerset Pharmaceuticals, Inc[US]
本社Tampa, Florida; Mylan Laboratories, Inc.(NYSE:MYL)とWatson Pharmaceuticals, Inc(NYSE:WPI)の合弁会社[50:50] 設立 1986
●Somerset Pharmaceuticals, Inc - http://www.somersetpharm.com/ ●Deprenyl Information Deprenyl Labeling ★Parkinson's Information -http://www.parkinsonsinfo.com/ ●Healthcare Professionals
Laboratorios Sophia S.A. de C.V[ME]
■Laboratorios Sophia S.A. de C.V[ME]
- http://sophia.com.mx/ [会社概要] ★ニュース Sirion Therapeutics Acquires U.S. License To Develop New Ophthalmic Compound [2006.7.24] - ST-603(cyclosporine) [Tenby Pharma Inc] - 8-K - For 9/12/06- - 当社Tenby Pharma Incは2006.1設立。 2006.9.13 Sirion Therapeutics, Inc., を完全子会社とした。 Tenby Pharma Incは2006.11.30社名をSirion Holdings, Inc.に変更。 SIRION HOLDINGS, INC. Annual Report [3/30/2007 ] ・ ST-603. ST-603 is a compound, with the active ingredient cyclosporine-A, which we are developing for use with the Sophisen ocular delivery system, a carrier of ophthalmic drug products. We began a clinical program with this product in the first quarter of 2007. We are evaluating options in a number of disease states, including dry eye syndrome. We license the exclusive rights to ST-603 in the U.S., Puerto Rico, Guam, the U.S. Virgin Islands and other U.S. territories and possessions from Laboratorios Sophia, S.A. de C.V. pursuant to a license agreement. In exchange for such license rights, we have committed to use our reasonable efforts to develop, market and promote this compound at our own expense in the geographic areas covered by the license, and we may be required to make payments based on the achievement of research milestones and royalties on sales, if any. [ISTA Pharmaceuticals]10-K/A - For 12/31/02- - Vitrase(R)(ovine hyaluronidase)をLaboratorios Sophia S.Aからライセンス Pharmacy Choice －8/24/06 - Sirion Therapeutics acquires U.S. license to develop cyclosporine A ophthalmic compound 2006 AUG 23 - -- Sirion Therapeutics, Inc., an ophthalmic-focused pharmaceutical company, announced that it has reached an exclusive licensing agreement with Laboratorios Sophia S.A. de C.V. [The Dry Eye Zone]The Dry Eye Digest - Clinical Trials SIRION/ST-603: (Added May 2007) Sirion Therapeutics announced May 1 that it was starting Phase III clinicals on its cyclosporine dry eye therapy ST-603. Click here for press release. ★ST-603文献 Characterization of the Novel Ophthalmic Drug Carrier Sophisen in Two of Its Derivatives: 3A Ofteno(TM) and Modusik-A Ofteno(TM) Drug Development and Industrial Pharmacy, Volume 31, Number 3, Number 3/2005 , pp. 263-269(7) 中等度～重症ドライアイで涙液産生を増加させる。 INTERNATIONAL SOCIETY OF DACRYOLOGY AND DRY EYE(ISD&DE). - 8th Congress - POSTER ABSTRACT PRESENTATIONS GONZALEZ, J.R. Laboratorios Sophia - TX 77030 GUADALAJARA (MEXICO) Cyclosporine-A Level in Serum after Topical Application of Eye Drops from Modusik-A Ofteno? L.M. BAIZA-DURAN; J.A. RODRIGUEZ-TREVILLA; M.M. GONZALEZ-LOMELI; R. TORNERO-MONTANO Laboratorios Sophia (Guadalajara, Mexico) Abstract:BACKGROUND: Cyclosporine-A (CsA) is a peptide with potent immunosuppressive activity. Several studies indicate that CsA affects mainly proliferating T-cells. CsA has been used in ophthalmology, to improve some conditions related to dry eye syndrome. Using CsA can promote natural tears production.
AIMS: To evaluate the systemic absorption of CsA after the topical installation of Modusik-A Ofteno? eye drops used in the treatment of dry eye syndrome.
METHODS: Modusik-A Ofteno? consists of 0.1% CsA associated to Sophisen? (US patent 6,071,958). 1 ml blood samples were obtained from 26 patients who received Modusik-A Ofteno? eye drops each 12 hours during a period from 3 to 6 months. Sera from blood samples were processed for CsA with (FPIA) Fluorescence Polarization Immunoassay with antibodies against Cyclosporine-A.
RESULTS: Twenty-six patients were included in this study, all of them signed an informed consent and were receiving CsA solution eye drops through 3 to 6 months. The mean value of CSA level in sera detected was of 1.75 ng/mL with a Standard deviation +/- 2.58 in a range 0f 0 to 9, distributed as follow 73% (19 patients) sera level was between 0 and 2 ng/mL, 11.5% (3 patients) Shown between 3 and 4ng/mL, 7.7% (2 patients) between 5 and 6 ng/mL, 3.8% (1 patient) between 7 and 8 ng/mL and 3.8% (1 patient) between 9 and 10 ng/mL.
CONCLUSIONS: The results suggest that the systemic absorption of CsA when is applied as eye drops is minimum if we compare it with the blood level of CsA during treatment to avoid organ transplant reject or some others immunologic diseases management. This indicates that topical application of Modusik-A Ofteno? does not reach risky CsA sera levels.GONZALEZ, J.R.
Laboratorios Sophia - TX 77030 GUADALAJARA (MEXICO)Creatinine and Urea Sera Levels Determination after 0.1% Cyclosporine Eyedrops Instillation
L.M. BAIZA-DURAN; J.A. RODRIGUEZ-TREVILLA; M.M. GONZALEZ-LOMELI; R. TORNERO-MONTANO
Laboratorios Sophia (Guadalajara, Mexico)Abstract:
PURPOSE: To determine if kidney function is affected by instillation of 0.1% Cyclosporine-A (CsA) eye drops, serum creatinine and urea levels were determined.
METHODS: The study included 40 healthy volunteers with no eye problems. All read and signed an informed consent letter. Each volunteer received one drop of 0.1% cyclosporine (w/v) on each eye, twice a day for 60 days. Blood samples were analyzed for creatinine and urea levels before and after the 60 days of treatement.
RESULTS: The average baseline serum creatinine level was 0.94 mg/dl, and urea was 32.5 mg/dl. After 60 days of CsA treatment, the data for creatinine and urea were 0.89 mg/dl and 29.1 mg/dl respectively. The results showed no evidence of changes.
CONCLUSIONS: After 60 days of 0.1% (w/v) CsA eye drops instillation, creatinine and urea sera levels do not indicate a risky condition for kidney health.--------------------------------------------------------------------------------
GONZALEZ, J.R.
Laboratorios Sophia - TX 77030 GUADALAJARA (MEXICO)Safety Efficacy and Tolerance Clinical Evaluation of a 0.1% Cyclosporine-A Eyedrops Compared to those in 0.05% Cyclosporine-A and Placebo as Treatment for Moderated to Severe Dry Eye Syndrome
L.M. BAIZA-DURAN; J.A. RODRIGUEZ-TREVILLA; M.M. GONZALEZ-LOMELI; R. TORNERO-MONTANO
Laboratorios Sophia (Guadalajara, Mexico)Abstract:
INTRODUCTION: Cyclosporine-A (CsA) can improve tears production in moderated to severe dry eye patients even without Sjogren syndrome, which turn dry eye treatment in an alternative to treat them instead of lubricants eyedrops which are limited to improve symptoms, CsA promotes tears production with all its characteristics, properties and advantages.
PURPOSE: To determine and compare safety, efficacy and tolerance of two different concentrations of CsA aqueous solution and placebo eyedrops for treatment of patients with dry eye syndrome.
METHODS: We compared the effects of 0.1% CsA (group A), 0.05% CsA (group B), and vehicle or placebo (group C), were evaluated symptoms and signs in patients affected by moderated to severe dry eye syndrome. This was a 120 days multicenter, randomized, double-blind clinical trial was preceded by two weeks wash-out period.
RESULTS: Patients receiving Modusik-A OftenoO (0.1% Cyclosporine) eye drops improved 72% in Schirmer I test compared to its own baseline, while 0.05% Cyclosporine improved 60.09% and placebo improved 32.2%. Also with Modusik-A OftenoO corneal surface conditions improved in 100% of the patients with moderated to severe dry eye syndrome. Compared to Placebo, patients with Modusik-A OftenoO improved 85% more in foreign body sensation. Also, burn sensation diminished 55% more when Modusik-A OftenoO compared to placebo. Dryness sensation diminished 40% in patients who used Modusik-A OftenoO compared to placebo. Weeping diminished 40% in patients with dry eye syndrome.
CONCLUSIONS: CsA reduced complaints and improved major ocular signs in patients suffering from moderate to severe dry eye syndrome. The group treated with 0.1% CsA aqueous solution outperformed the other 2 study groups.
Key words: Dry eye, Cyclosporine A, randomized clinical trial.--------------------------------------------------------------------------------
GONZALEZ, J.R.
Laboratorios Sophia - TX 77030 GUADALAJARA (MEXICO)In Vitro Study of Corneal Retention of Cyclosporine-A from Different Formulations
J.D. QUINTANA-HAU; L.M. BAIZA-DURAN; J.A. RODRIGUEZ-TREVILLA; M.M. GONZALEZ-LOMELI; R. TORNERO-MONTANO
Laboratorios Sophia (Guadalajara, Mexico)Abstract:
INTRODUCTION: Cyclosporine-A (CsA) is valuable in the treatment of diseases, such as dry eye, uveitis and corneal transplantation. Its acts by selective inhibition of interleukin-2 release during the activation of T-cells and causes suppression of the cell-mediated immune response. Several attempts were made to improve ocular CsA penetration. Modusik-A OftenoR is a new product developed by Laboratorios Sophia, which contains Cyclosporine-A.
PURPOSE: Compare the amount of CsA retained in cornea using an in vitro model with different formulations.
METHODS: It was compared Modusik-A OftenoR against Restasis? (0.05% CsA in castor oil; Allergan, Irvine CA) and Modusik-A OftenoR against 2.0% CsA in olive oil as vehicle, by In Vitro passive diffusion.
RESULTS: Modusik-A OftenoR showed to be a better source when the total amount of CsA in the cornea was compared to 0.10% o CsA in olive oil. When the concentration of CsA was increased to 2.0% in olive oil the concentration of the drug detected in cornea was similar compared to Modusik-A. Using the same method two different concentrations of CsA (0.10% and 0.05% Modusik-A OftenoR) were compared to Restasis. A slight increase of CsA in cornea was observed when the donor was 0.10% Modusik-A OftenoR as donor.
CONCLUSIONS: Challenging 2.0% CsA in olive oil and Modusik-A OftenoR by passive diffusion we did not find an improvement in amount of CsA in cornea when an oil formulation was used as a donor. It appears that cornea has restricted passive diffusion capability for CsA. These results suggest that Modusik-A OftenoR is a proper formulation to deliver CsA to the eye.
Key words: Dry eye, cyclosporine A, passive diffusion.
●Laboratorios Sophia S.A. de C.V[ME] ■Professional ●Products ■General ●Products ●Eye care
Special Products Limited[UK]
■Special Products Limited[UK]
- http://www.specialproducts.biz/; 本社in Surrey 1997 設立。 by Dr Graham March ●会社決算
(￡ milllion) 2006予 2005 2004 2003 2002 2001 売上高 3.5 2.3 1.5 1.0 開発中新薬数 39 26 18
●Special Products Limited[UK] - http://www.specialproducts.biz/ ●News ●Health Professionals[要登録] * Product List * Product Information * Online Ordering ●製品 Epistatus : Buccal midazolam KidNaps : melatonin liquid
製品名
(成分)適応 承認状況 競合 備考 Revocon 25mg Tablets
(tetrabenazine)used for the treatment of diseases , which cause jerky, irregular uncontrolled movements such as Huntington's chorea, senile chorea, tardive dysinesia and hemiballismus. Revocon 25mg Tablets should only be used in tardive dykinesia when other treatment options have failed Pharma Registration International Limitedが英2008.4.17 Xenazine(Life Health Ltd)のジェネリック Epistatus
(Buccal midazolam)
()
()
●Epistatus関連資料 United Kingdom Psychiatric Pharmacy Group[UKPPG] - ADMINISTRATION OF EPISTATUS R BUCCAL MIDAZOLAM - 10MG (BASE) IN 1ML SUGAR-FREE SYRUP TO PEOPLE WHO HAVE EPILEPSY[pdf,11p] - COLCHESTER PRIMARY CARE TRUST LEARNING DISABILITY SERVICES [West Midlands Medicines Information Service]Caution: oral / buccal midazolam for serious epileptic seizures, potential for dose confusion[pdf,3p] ●[NHS Lothian Joint Formulary] 4.8.1 Control of epilepsy
4.8.2 Treatment of prolonged seizures and status epilepticus
Status epilepticus is defined as seizures which last for more than 30 minutes or a series of seizures which takes place without the patient regaining consciousness in between them. Step 1 (in community)
First choice:
Second choice:
diazepam rectal solution
midazolam* buccalStep 2 (in hospital) lorazepam injection
or diazepam injection (emulsion)
or midazolam* buccalStep 3 (in hospital) phenobarbital (phenobarbitone) inj.
or phenytoin injectionStep 4 admit to ITU *Midazolam buccal is reserved for patients with a pre-planned individual protocol ★Dose
Diazepam rectal solution 10mg/2.5mL: usually 10mg.
★Prescribing notes Community
- Midazolam buccal liquid 10mg/mL (Epistatus®): drawn up via oral syringe, and administered by the buccal route in the treatment of status epilepticus (not intravenous for this indication), 10mg as a single dose (or 5mg if under 50kg) according to individual patient protocol.
- Lorazepam injection 4mg/mL: by intravenous injection (into large vein), 4mg.
- Diazepam injection (emulsion) 5mg/mL (Diazemuls®): by intravenous injection, 10-20mg at a rate of 0.5mL (2.5mg) per 30 seconds, repeated if necessary after 30-60 minutes.
- Phenobarbital injection 200mg/mL in propylene glycol 90% and water for injections 10%: by intravenous injection (dilute injection 1 in 10 with water for injections), 10mg/kg at a rate of not more than 100mg/minute; max 1g.
- Phenytoin sodium injection 50mg/mL: by slow intravenous injection or infusion (with blood pressure and ECG monitoring), 15mg/kg at a rate not exceeding 50mg per minute, as a loading dose. Maintenance dose may be required.
- Where possible, treatment should be initiated in the community prior to hospital.
- A possible underlying cause (e.g. hypoglycaemia, hypoxia etc) must be considered.
- The first episode of status epilepticus should be treated with rectal diazepam if available, and an ambulance should be called.
- Treatment should be given if convulsion lasts longer than 5 minutes. Buccal midazolam is an alternative to rectal diazepam. This drug should be given by a trained healthcare professional or carer, according to the individual agreed protocol drawn up for the patient by the specialist.
- Information regarding training for the administration of buccal midazolam can be obtained by contacting the epilepsy specialist nurses at 0131 537 2089.
- Midazolam buccal liquid 10mg/mL (Epistatus®) is available on a named patient basis from Special Products Limited. Note that Epistatus® is a different strength to midazolam injection.
Hospital
- In some cases, rectal paraldehyde may be administered in the community for prolonged seizures, according to individual patient protocol.
- If still fitting at 10 minutes and, if not already in hospital, call an ambulance. A second dose may be given sooner if resuscitation facilities are available.
- If convulsion continues beyond 30 minutes (status epilepticus), patient will need hospitalisation and preferably admission to ITU.
- Although the BNF recommends lorazepam injection, this requires refrigeration and may therefore not be suitable for GP use.
- Clobazam may be prescribed to prevent status epilepticus in patients with a previous history of status or who are known to be at risk if their seizures accelerate or begin to cluster. It may also be prescribed for those whose seizures occur or accelerate at certain times e.g. during menstruation or intercurrent infections. Prescriptions should be endorsed 'SLS'.
●PubMed midazolan buccal =30件
1: Walker DM, Teach SJ. Update on the acute management of status epilepticus in children.
Curr Opin Pediatr. 2006 Jun;18(3):239-244.
PMID: 16721142 [PubMed - as supplied by publisher]
2: Hindley D, Jameson H. Buccal midazolam: is a test dose in hospital needed?
Arch Dis Child. 2006 Jun;91(6):544-5. No abstract available.
PMID: 16714742 [PubMed - indexed for MEDLINE]
3: Wiznitzer M. Buccal midazolam is effective for acute treatment of seizures.
J Pediatr. 2006 Jan;148(1):143. No abstract available.
PMID: 16440479 [PubMed]
4: Baysun S, Aydin OF, Atmaca E, Gurer YK. A comparison of buccal midazolam and rectal diazepam for the acute treatment of seizures.
Clin Pediatr (Phila). 2005 Nov-Dec;44(9):771-6.
PMID: 16327963 [PubMed - indexed for MEDLINE]
5: Eriksson K, Kalviainen R. Pharmacologic management of convulsive status epilepticus in childhood.
Expert Rev Neurother. 2005 Nov;5(6):777-83. Review.
PMID: 16274335 [PubMed - indexed for MEDLINE]
6: Scott RC. Buccal midazolam as rescue therapy for acute seizures.
Lancet Neurol. 2005 Oct;4(10):592-3. No abstract available.
PMID: 16168926 [PubMed - indexed for MEDLINE]
7: Horiuchi T, Kawaguchi M, Kurehara K, Kawaraguchi Y, Sasaoka N, Furuya H. Evaluation of relatively low dose of oral transmucosal ketamine premedication in children: a comparison with oral midazolam.
Paediatr Anaesth. 2005 Aug;15(8):643-7.
PMID: 16029398 [PubMed - indexed for MEDLINE]
8: McIntyre J, Robertson S, Norris E, Appleton R, Whitehouse WP, Phillips B, Martland T, Berry K, Collier J, Smith S, Choonara I. Safety and efficacy of buccal midazolam versus rectal diazepam for emergency treatment of seizures in children: a randomised controlled trial.
Lancet. 2005 Jul 16-22;366(9481):205-10.
PMID: 16023510 [PubMed - indexed for MEDLINE]
9: Wiznitzer M. Buccal midazolam for seizures.
Lancet. 2005 Jul 16-22;366(9481):182-3. No abstract available.
PMID: 16023491 [PubMed - indexed for MEDLINE]
10: Pang T, Hirsch LJ. Treatment of Convulsive and Nonconvulsive Status Epilepticus.
Curr Treat Options Neurol. 2005 Jul;7(4):247-259.
PMID: 15967088 [PubMed - as supplied by publisher]
11: Body R, Ijaz M. Best evidence topic report. Buccal midazolam as an alternative to rectal diazepam for prolonged seizures in childhood and adolescence.
Emerg Med J. 2005 May;22(5):364-5. Review.
PMID: 15843707 [PubMed - indexed for MEDLINE]
12: Kwong KL, Chang K, Lam SY. Features predicting adverse outcomes of status epilepticus in childhood.
Hong Kong Med J. 2004 Jun;10(3):156-9.
PMID: 15181218 [PubMed - indexed for MEDLINE]
13: Maegaki Y, Ogura K, Ohno K. [Buccal midazolam for treatment of status epilepticus or repetitive seizures]
No To Hattatsu. 2004 Mar;36(2):155-7. Japanese. No abstract available.
PMID: 15031993 [PubMed - indexed for MEDLINE]
14: Armijo JA, Herranz JL, Pena Pardo MA, Adin J. [Intranasal and buccal midazolam in the treatment of acute seizures]
Rev Neurol. 2004 Mar 1-15;38(5):458-68. Review. Spanish.
PMID: 15029526 [PubMed - indexed for MEDLINE]
15: Wilson MT, Macleod S, O'Regan ME. Nasal/buccal midazolam use in the community.
Arch Dis Child. 2004 Jan;89(1):50-1.
PMID: 14709505 [PubMed - indexed for MEDLINE]
16: Kutlu NO, Dogrul M, Yakinci C, Soylu H. Buccal midazolam for treatment of prolonged seizures in children.
Brain Dev. 2003 Jun;25(4):275-8.
PMID: 12767460 [PubMed - indexed for MEDLINE]
17: Ng KC, Ang SY. Sedation with ketamine for paediatric procedures in the emergency department--a review of 500 cases.
Singapore Med J. 2002 Jun;43(6):300-4.
PMID: 12380727 [PubMed - indexed for MEDLINE]
18: Zhang J, Niu S, Zhang H, Streisand JB. Oral mucosal absorption of midazolam in dogs is strongly pH dependent.
J Pharm Sci. 2002 Apr;91(4):980-2.
PMID: 11948536 [PubMed - indexed for MEDLINE]
19: Wassner E, Morris B, Fernando L, Rao M, Whitehouse WP. Intranasal midazolam for treating febrile seizures in children. Buccal midazolam for childhood seizures at home preferred to rectal diazepam.
BMJ. 2001 Jan 13;322(7278):108. No abstract available.
PMID: 11203721 [PubMed - indexed for MEDLINE]
20: Scott RC, Besag FM, Neville BG. Intranasal midazolam for treating febrile seizures in children. Buccal midazolam should be preferred to nasal midazolam.
BMJ. 2001 Jan 13;322(7278):107. No abstract available.
PMID: 11154640 [PubMed - indexed for MEDLINE]
21: Camfield PR. Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomised trial.
J Pediatr. 1999 Sep;135(3):398-9. No abstract available.
PMID: 10523148 [PubMed - indexed for MEDLINE]
22: Chattopadhyay A, Morris B, Blackburn L, Wassmer E, Whitehouse W. Buccal midazolam and rectal diazepam for epilepsy.
Lancet. 1999 May 22;353(9166):1798. No abstract available.
PMID: 10348017 [PubMed - indexed for MEDLINE]
23: Scheepers M, Comish S, Cordes L, Clough P, Scheepers B. Buccal midazolam and rectal diazepam for epilepsy.
Lancet. 1999 May 22;353(9166):1797-8. No abstract available.
PMID: 10348016 [PubMed - indexed for MEDLINE]
24: Ellis SJ, Baddely L. Buccal midazolam and rectal diazepam for epilepsy.
Lancet. 1999 May 22;353(9166):1796-7. No abstract available.
PMID: 10348015 [PubMed - indexed for MEDLINE]
25: Scott RC, Besag FM, Neville BG. Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomised trial.
Lancet. 1999 Feb 20;353(9153):623-6.
PMID: 10030327 [PubMed - indexed for MEDLINE]
26: Holmes GL. Buccal route for benzodiazepines in treatment of seizures?
Lancet. 1999 Feb 20;353(9153):608-9. No abstract available.
PMID: 10030323 [PubMed - indexed for MEDLINE]
27: Schwagmeier R, Alincic S, Striebel HW. Midazolam pharmacokinetics following intravenous and buccal administration.
Br J Clin Pharmacol. 1998 Sep;46(3):203-6.
PMID: 9764959 [PubMed - indexed for MEDLINE]
28: Scott RC, Besag FM, Boyd SG, Berry D, Neville BG. Buccal absorption of midazolam: pharmacokinetics and EEG pharmacodynamics.
Epilepsia. 1998 Mar;39(3):290-4.
PMID: 9578047 [PubMed - indexed for MEDLINE]
29: Biddle C, Gilliland C. Transdermal and transmucosal administration of pain-relieving and anxiolytic drugs: a primer for the critical care practitioner.
Heart Lung. 1992 Mar;21(2):115-24.
PMID: 1544805 [PubMed - indexed for MEDLINE]
30: Alfonzo-Echeverri E, Troutman KC, George W. Absorption and elimination of midazolam by submucosal and intramuscular routes.
Anesth Prog. 1990 Nov-Dec;37(6):277-81.
PMID: 2097906 [PubMed - indexed for MEDLINE]
●melatonin Liquid関連資料 米国で健康食品として販売。 ●Natrol, Inc. -http://www.natrol.com/ 1980年創立の健康食品メーカー。栄養剤200製品以上、小売店54,000で販売。 NASDAQ上場。 年間売上高(2005) $67.5 MILLION Melatonin Liquid ●PubMed melatonin liquid =324件 めぼしい文献がない。
■SuperGen, Inc.[米]
- http://www.supergen.com/?main=home ; 設立 1991.3.6 IPO 1996.3.16 NASDAQ:SUPG 2006.4 Montigen Pharmaceuticals, Incを買収。 MP-470(a multi-targeted Tyrosine Kinase inhibitor("TKI"),MP-529(an Aurora-A Kinase inhibitor)共に前臨床で、2007年臨床入り予定。[開発・ライセンス収入] (2006)$20.0 million はDacogenのFDA承認に伴うMGIから。$5 million はMGIサブライセンスから。 (2005)$13.3 million は、MGIから。(2004)MGI [ロイヤルティ] (2006)MGI [販売契約等収入] (2005) NipentのAbbottとの販売契約終了に伴う。1999年から５年間の契約。
($ 000) 2006 2005 2004 2003 2002 備考 製品売上高 9,563(-40.5) 16,059(+22.3) 13,127(+14.8) 11,437(-19.4) 14,188 主にNipent 開発・ライセンス収入 25,093(+87.9) 13,353(-29.2) 18,866 - - 主にDacogen(MGI) ロイヤルティ 3,427(-) - - - - 販売契約等収入 - 757(-) - 57(-94.7) 1,081 総収入 38,083 30,169 31,993 11,494 15,269 売上原価 2,003 3,051 4,135 3,865 4,491 営業利益 (21,496) (15,987) (24,920) (43,119) (42,642) 経常利益 当期純利益 (16,487) (14,482) (46,860) (53,470) (49,471) 研究開発費 16,544 15,059 23,978 26,312 29,895 取得研究開発費 16,318 - - - - 従業員数[連結] 89 83 109 Nipent 8,400 15,000 11,400 10,100 12,600 [pentostatin注]hairy-cell leukaemia治療薬 うち欧州 509 1,000 1,500 315 400 [] []
●SuperGen, Inc.[米] - http://www.supergen.com/?main=home ●製品 主要製品は３つ。 ★Dacogen(R) (decitabine) for injection - 1999.9 Pharmachemieから取得。 - 2006年FDA承認。 2006.5.3 myelodysplastic syndromes("MDS"). 2004.9 MGI Pharmaに全世界の開発・製造販売権を許諾。($40.0 million) 欧州は2004.10.25の審査でデータを追加要求され、2005.11 申請取り下げ。 2006.7 MGIはDacogenの北米以外の開発販売権をCilag GmbH(J&J子会社)にサブライセンス。 sublicensesについては当社は50%を受け取る。 ★Orathecin(TM) (rubitecan) capsules - camptothecin系経口剤で1997年Stehlin Foundation for Cancer Research からライセンスを受けた。 - 2005.1申請取り下げ。 2004.1 迅速承認により膵臓癌の適応症でFDA申請。 欧州は2004.7申請、2006.1取り下げ。 From 1998 through 2006 we have spent approximately $72.5 million ★Nipent(R) (pentostatin for injection) - 1996年にWarner-LambertのParke-Davis事業部から取得したもの。 - 2006年にMayne Pharmaに全権を売却 ●Pipeline ■Investors ●News Releases SuperGen Reports 2006 Fourth Quarter and Year-End Financial Results[2007.3.14] Nipent(R) Acquisition by Hospira is Complete[2007.4.3] - Nipent(R) (pentostatin for injection)はhairy-cell leukaemia治療薬で、その全世界の権利を総額US$42 millionでMayne Pharmaに売却したわけだが、Myaneは2007.2にHospiraに買収された。 Mayne Pharma Acquires Remaining Nipent(R) Rights[2006.11.27] - 先にNipent(R) (pentostatin for injection)の北米の権利を売却したが、全世界の残りの権利をUS $8 millionで売却。 Nipent(R) の2005年度欧州売上高は約US $5 million。(英独仏伊など) Mayne Pharma's Purchase of SuperGen's North American Oncology Products Completes[2006.8.23] Mayne Acquires SuperGen's North American Oncology Products[2006.6.21] - Nipent(R) (pentostatin for injection) and SurfaceSafe(TM) の北米権をMayne Pharma Limited (ASX: MYP)に売却。US$34 million SuperGen Completes Contract to Transition Wyeth Distribution of Nipent(R), Outside of the U.S.[2006.6.6] - Nipentは欧州でWyethが販売してきたが2006.6.1で早期打ち切り、Supergen英国子会社EuroGen Pharmaceuticals Limitedが引き継ぐ。 Supergenは違約金$2.1 million を支払う。 SuperGen Receives U.S. Patent For Nipent(R)(Pentostatin For Injection)[2006.6.2] U.S. FDA Approves Dacogen(TM) (Decitabine) For Injection[2006.5.3] ●SEC Filings 10-K Annual report 2006[2007.3.16] - [pdf,113p] ●Annual Reports 2006 Annual Report[pdf,126p] ●
■Tercica, Inc.[US]
- http://www.tercica.com/index.html ●会社決算★Ipsen SAへのライセンス Increlexについては米加日を除く全世界の開発・販売権をライセンス。 IpsenはSomatuline(R) Autogel に関してTercica社に米加のライセンス。 ★Increlex(TM) [2006] 米国発売2006.1.3 we believe that approximately 24,000 children in each of the United States and Western Europe suffer from Primary IGFD. We estimate that a total of 6,000 children in each of the United States and Western Europe have severe Primary IGFD. The Company markets Increlex(TM) as a long-term replacement therapy for the treatment of children with severe primary insulin-like growth factor deficiency, or severe Primary IGFD, or with growth hormone gene deletion who have developed neutralizing antibodies to growth hormone. The Company obtained approval for the long-term treatment of severe Primary IGFD, from the U.S. Food and Drug Administration, or FDA, in August 2005. We are currently conducting a Phase IIIb clinical trial for the use of Increlex(TM) for the treatment of children with Primary IGFD. In January 2006, the Company launched Increlex(TM) in the United States. Increlex(TM) generated net revenues of $1.3 million in 2006.
($ 000) 2006 2005 2004 2003 2002 2001 備考 製品売上高 1,315 - - - - Increlex ライセンス 194 - - - - 収入 計 1,509 - - - - 営業利益 (86,440) (47,500) (41,887) (25,750) (9,023) 経常利益 (82,376) (46,233) (41,002) (24,423) (8,952) 当期純利益 (82,997) (46,233) (41,002) (25,423) (8,952) 研究開発費 42,034 21,587 29,335 20,916 7,045 従業員数[連結] In December 2005, the Company submitted a Marketing Authorization Application, or MAA, in the European Union for the long-term treatment of growth failure in children with severe Primary IGFD or with growth hormone gene deletion who have developed neutralizing antibodies to growth hormone. The Company expects to receive an opinion from the Committee for Medicinal Products for Human Use on the Increlex(TM) MAA in the second quarter of 2007. Pursuant to the Company's worldwide strategic collaboration with Ipsen that was finalized in October 2006, the Company granted to Ipsen and its affiliates the exclusive right under the Company's patents and know-how to develop and commercialize Increlex(TM) in all countries of the world except the United States, Japan, Canada, and for a certain period of time, Taiwan and certain countries of the Middle East and North Africa, for all indications, other than treatment of central nervous system and diabetes indications.
★Somatuline(R) Autogel(R) (lanreotide) [2006] 米国申請2006 by Ipsen SA; カナダ承認2006.7(for the treatment of acromegaly) by Ipsen. We believe that a total of approximately 15,000 people in the United States and Canada are estimated to have acromegaly. It is most commonly found in middle-aged adults.Somatuline R Autogel R has marketing authorizations in over 50 countries for the treatment of acromegaly and neuroendocrine tumors. In 2006, Somatuline R and Somatuline R Autogel R generated worldwide sales of Eur 92.2 million (approximately $120 million), up 12.8% versus 2005. In its main markets in Europe, Somatuline R Autogel R has achieved a 30% to 50% market share of the acromegaly market varying from country-to-country.Pursuant to the worldwide strategic collaboration with Ipsen, the Company has the exclusive right under Ipsen's patents and know-how to develop and commercialize Somatuline R Autogel R in the United States and Canada for all indications other than opthalmic indications. In July 2006, Somatuline R Autogel R was approved for marketing by Health Canada for the treatment of acromegaly and is currently in the reimbursement review process. Acromegaly is a hormonal disorder that results when a tumor in the pituitary gland produces excess growth hormone, resulting in overproduction of insulin-like growth factor-1 (IGF-1) and excessive growth. In October 2006, Ipsen submitted an NDA to the FDA for the use of Somatuline R Autogel R for the treatment of acromegaly. The FDA accepted the NDA on December 30, 2006, and the Prescription Drug User Fee Act, or PDUFA, date for Somatuline R Autogel R for the treatment of acromegaly is August 30, 2007
★Key Relationships - Genentech [2006]
rhIGF-1 . We entered into a U.S. License and Collaboration Agreement with Genentech in April 2002, which was amended in July and November 2003. In addition, we entered into an International License and Collaboration Agreement with Genentech in July 2003, which expands certain of the rights granted to us under the U.S. License and Collaboration Agreement to the remaining territories of the world outside of the United States. Under these agreements, we have certain rights and licenses to Genentech's intellectual property to research, develop, use, manufacture and market rhIGF-1, alone or in combination with IGF binding protein-3, which we refer to in this document as IGFBP-3, for a broad range of indications. The rights are exclusive with respect to our development and sale of rhIGF-1 and non-exclusive with respect to our manufacture of rhIGF-1. Indications not covered by our licenses from Genentech include diseases and conditions of the central nervous system. In addition, we need to enter into a written agreement with another company if we desire to commercialize rhIGF-1 for diabetes outside of the United States.
Under both the U.S. License and Collaboration Agreement and the International License and Collaboration Agreement, Genentech agreed to transfer to us its pre-clinical and clinical data related to rhIGF-1. This includes data resulting from extensive animal testing as well as Phase I, Phase II and Phase III clinical trials with respect to rhIGF-1. In addition, under these agreements Genentech agreed to transfer its manufacturing technology and know-how to us. In consideration of this transfer, we paid Genentech $1.0 million in cash and approximately $4.1 million in Series A preferred stock upon execution of the U.S. License and Collaboration Agreement. We paid Genentech $1.7 million upon execution of the International License and Collaboration Agreement and $1.4 million related to the license to Genentech's rights to IGF-1 combined with IGFBP-3. In connection with the approval of our NDA in August 2005, we paid Genentech a $1.0 million milestone payment related to the U.S. License and Collaboration Agreement. We also agreed to pay to Genentech royalties on the sales of rhIGF-1 products and certain one-time payments upon the occurrence of specified milestone events, such as attaining rhIGF-1 indication approvals and aggregate sales levels with respect to rhIGF-1. We are subject to the following milestone payments to Genentech as of December 31, 2006:
・ In addition to the amounts already paid to Genentech, if we achieve all of the additional milestones for rhIGF-1 under the U.S. License and Collaboration Agreement and the International License and Collaboration Agreement, we will owe Genentech up to an aggregate of approximately $33.0 million.
・ If we develop rhIGF-1 in combination with IGFBP-3, we would be subject to these same milestone events and, upon achievement of all of the milestones, would owe Genentech up to an additional aggregate of approximately $32.5 million.
Accordingly, we would owe Genentech up to an aggregate of approximately $65.5 million in milestone payments if we achieved all of these milestone events for both rhIGF-1 and for rhIGF-1 in combination with IGFBP-3. Both agreements require us to fulfill certain obligations to maintain our licenses.
Under the U.S. License and Collaboration Agreement, Genentech has exclusively licensed to us its right to develop and commercialize rhIGF-1 products in the United States for all indications other than diseases and conditions of the central nervous system. Genentech has a right, the Opt-In Right, to elect, within a limited period of time following an NDA-enabling clinical trial, to participate jointly with us in the development and commercialization of rhIGF-1 products we develop for diabetes indications and for all non-orphan indications. Orphan indications are generally diseases or conditions that affect fewer than 200,000 individuals in the United States. If Genentech elects to exercise its Opt-In Right for a particular indication, Genentech will pay us more than 50% of the past development costs associated with that indication. In addition, after Genentech exercises its Opt-In Right for a particular indication, we would share with Genentech the ongoing net operating losses and profits resulting from the joint development and commercialization effort for that indication. Pursuant to this arrangement, we would fund less than 50% of such operating losses and we would receive less than 50% of any profits associated with any joint indication. In addition, if we elect to discontinue the development of rhIGF-1 products for diabetes or a substitute indication selected by us, subject to Genentech's consent, Genentech has the right to assume development of such indication. Any substitute indication agreed to by Genentech, under the terms of the current agreement, must have a potential market greater than $250.0 million and not be an indication for the central nervous system. In such event, our rights under the agreement for such indication would terminate and Genentech would be granted a non-exclusive license under our rhIGF-1 intellectual property and technology to manufacture, use and sell rhIGF-1 products for diabetes, or if applicable the substitute indication, subject to an obligation to pay us milestone payments and/or royalties to be negotiated by Genentech and us in good faith on sales of these products.
With respect to those indications in the United States for which Genentech does not have an Opt-In-Right or for which Genentech has not exercised its Opt-In-Right to jointly develop and commercialize rhIGF-1, we have the final decision on disputes relating to development and commercialization of rhIGF-1. With respect to those indications in the United States for which Genentech has exercised its Opt-In-Right, or for which its Opt-In-Right has not expired or been waived by Genentech, Genentech has the final decision on disputes relating to development and commercialization of rhIGF-1.
Under the International License and Collaboration Agreement, Genentech has exclusively licensed to us its right to develop and commercialize rhIGF-1 products outside of the United States for all indications other than diseases and conditions of the central nervous system. In addition, we need to enter into a written agreement with another company if we desire to commercialize rhIGF-1 for diabetes outside of the United States. Unlike the U.S. License and Collaboration Agreement, Genentech does not have the right to participate in any of our development or commercialization efforts for rhIGF-1 products outside of the United States.
Upon an uncured material breach of either the U.S. License and Collaboration or the International License and Collaboration Agreement, the non-breaching party may terminate the agreement. We also have the right to terminate either agreement at our sole discretion upon 60 days prior written notice to Genentech. If Genentech terminates either agreement because of our material breach, or if we terminate either agreement for any reason other than a material breach by Genentech, the rights and licenses granted to us under the respective agreement would terminate. In such event, Genentech would be granted a non-exclusive license under our rhIGF-1 intellectual property and technology to manufacture, use and sell rhIGF-1 products, subject to an obligation to pay us royalties on sales of these products to be negotiated by Genentech and us in good faith.
★Key Relationships - Ipsen [2006]
On October 13, 2006, we completed the first closing of the transactions contemplated by the stock purchase and master transaction agreement we entered into with Ipsen in July 2006. At the closing, we issued 12,527,245 shares of our common stock to an affiliate of Ipsen for an aggregate purchase price of $77.3 million, a 30.0% premium to the Company's volume-weighted average closing stock price over the preceding 15 trading days ending on July 17, 2006, and issued to Ipsen a convertible note in the principal amount of $25.0 million and a warrant to purchase a minimum of 4,948,795 shares of our common stock, which warrant is exercisable at any time during the five-year period after the initial closing and carries an initial exercise price equal to $7.41 per share. Simultaneously with the initial closing, we and Ipsen (and/or affiliates thereof) entered into licensing agreements with respect to Somatuline(R) Autogel(R) and Increlex(TM) , and entered into certain other agreements, including an affiliation agreement with respect to certain corporate governance matters and providing Ipsen with the right to nominate a certain number of directors for election to our Board of Directors. Additionally, we effected an amendment to our amended and restated certificate of incorporation and adopted a rights agreement implementing a stockholder rights plan. The stock purchase and master transaction agreement we entered into with Ipsen in July 2006 also provides for the issuance by us of a second convertible note and a third convertible note to Ipsen in the principal amounts of Euro30.0 million (or $39.6 million at December 31, 2006) and $15.0 million, respectively, at the second closing thereunder. Each of the convertible notes we issued or that we may issue to Ipsen mature in October 2011 and carry a coupon of 2.5% per annum from the date of issuance, compounded quarterly, and are convertible into shares of our common stock at an initial conversion price per share equal to $7.41 per share (Euro5.92 per share with respect to the second convertible note). The number of shares that Ipsen can purchase by exercising the warrant can increase over time. As of December 31, 2006, Ipsen could purchase up to approximately 5,000,000 shares of our common stock by exercising the warrant.
Together with the shares issued at the initial closing, the conversion of all three convertible notes and the exercise of the warrant in full would enable Ipsen to acquire an ownership interest in us of approximately 40% on a fully diluted basis.
Pursuant to the licensing agreements we entered into with Ipsen (and/or affiliates thereof) in connection with the initial closing under the stock purchase and master transaction agreement, we granted to Ipsen and its affiliates exclusive rights to develop and commercialize Increlex(TM) in all countries of the world except the United States, Japan, Canada, and for a certain period of time, Taiwan and certain countries of the Middle East and North Africa, and Ipsen granted to us exclusive rights to develop and commercialize Somatuline(R) Autogel(R) in the United States and Canada. Further, we and Ipsen granted to each other product development rights and agreed to share the costs for improvements to, or new indications for, Somatuline(R) Autogel(R) and Increlex(TM) . In addition, we and Ipsen agreed to rights of first negotiation for our respective endocrine pipelines. Under the license and collaboration agreement with respect to Increlex(TM) , Ipsen made an upfront cash payment to us of Euro10.0 million or $12.4 million and has agreed to pay us a milestone of Euro15.0 million (or $19.8 million as of December 31, 2006) upon approval of the Increlex(TM) MAA in the European Union for the targeted product label. If Increlex(TM) is launched in Ipsen's territory, Ipsen would pay royalties to us on a sliding scale from 15% to 25% of net sales, in addition to a supply price of 20% of net sales of Increlex(TM) . Under the license and collaboration agreement with respect to Somatuline(R) Autogel(R) , we made an upfront payment of $25.0 million to Ipsen, which was financed through the issuance by us of the first convertible note to Ipsen at the initial closing under the stock purchase and master transaction agreement. If Somatuline(R) Autogel(R) is approved in the United States for the targeted product label (and the second closing under the stock purchase and master transaction agreement is consummated), we would make a milestone payment of Euro 30.0 million (or $39.6 million as of December 31, 2006) to Ipsen, which would be financed through the issuance by us of the second convertible note to Ipsen at the second closing. If the second closing is consummated, we would also issue the third convertible note to Ipsen and Ipsen would deliver $15.0 million to us, which would be used by us for working capital. Once Somatuline(R) Autogel(R) is launched in our territory, we would pay royalties to Ipsen, on a sliding scale from 15% to 25% of net sales, in addition to a supply price of 20% of net sales of Somatuline(R) Autogel(R) . For additional information on our collaboration with Ipsen, please refer to “Note 7 of the Notes to Financial Statements.
★Patents and Proprietary Rights [2006]
Our policy is to enforce our licensed patents to the extent our licensors have granted us such rights, and to protect our proprietary technology. We intend to continue to file U.S. and foreign patent applications to protect technology, inventions and improvements that are considered important to the development of our business. There can be no assurance that any of these patent applications will result in the grant of a patent either in the United States or elsewhere, or that any patents granted will be valid and enforceable, or will provide a competitive advantage or will afford protection against competitors with similar technologies. Our success could depend, in part, on our ability to obtain additional patents, protect our proprietary rights and operate without infringing third party patents. We will be able to protect our licensed patents or proprietary technologies from unauthorized use by third parties only to the extent that such patents or proprietary rights are covered by valid and enforceable patents or are effectively maintained as trade secrets and such third party does not have any valid defense.
We have licensed from Genentech certain intellectual property rights, including patent rights and pre-clinical and clinical data, and manufacturing know-how, to develop and commercialize rhIGF-1 worldwide for a broad range of indications. Such U.S. patents expire between 2010 and 2020. Our U.S. patent No. 6,331,414 B1 licensed from Genentech is directed to methods for bacterial expression of rhIGF-1 and expires in 2018. We have no equivalent European patent. The European Patent Office has determined that the claims of Genentech's corresponding European patent application are not patentable under European patent law in view of public disclosures made before the application was filed.
We have licensed from Ipsen their intellectual property rights, including patent rights and pre-clinical and clinical data, to develop and commercialize Somatuline(R) Autogel(R) in the United States and Canada for a broad range of indications. Such rights include U.S. patents for the formulation and for methods of using Somatuline(R) Autogel(R) that expire between 2015 and 2019. We do not have patent composition coverage on the lanreotide molecule (the active pharmaceutical ingredient of Somatuline(R) Autogel(R) ) alone.
There has been increasing litigation in the biopharmaceutical industry with respect to the manufacture and sale of new therapeutic products. The validity and breadth of claims in biotechnology patents may involve complex factual and legal issues for which no consistent policy exists. In particular, the patent protection available for protein-based products, such as rhIGF-1, is highly uncertain and involves issues relating to the scope of protection of claims to gene sequences and the production of their corresponding proteins.
There can be no assurance that our licensed patents will not be successfully circumvented by competitors. In particular, we do not have patent composition coverage on the rhIGF-1 protein alone, and we are aware that Chiron Corporation has developed a process to manufacture rhIGF-1 using yeast expression, rather than bacterial expression. In addition, the patent laws of foreign countries differ from those in the United States and the degree of protection afforded by foreign patents may be different from the protection offered by U.S. patents. Our competitors may obtain patents in the United States and Europe directed to methods for the manufacture or use of rhIGF-1 that may be necessary for us to conduct our business free from claims of patent infringement. We may not be able to license such patents on reasonable terms, if at all.
We may need additional intellectual property from other third parties to commercialize rhIGF-1 for diabetes. We cannot be sure that we will be able to obtain a license to any third party technology we may require to conduct our business.
In some cases, litigation or other proceedings may be necessary to defend against claims of infringement, to enforce patents licensed to us, to protect our know-how or other intellectual property rights or to determine the scope and validity of the proprietary rights of third parties. Any potential litigation could result in substantial cost to us and diversion of our resources. We cannot be sure that any of our licensed patents will ultimately be held valid. An adverse outcome in any litigation or proceeding could subject us to significant liability.
Declaratory judgments of invalidity against the patents asserted in any such actions could prevent us from using the affected patents to exclude others from competing with us.
We generally enter into confidentiality agreements with our employees and consultants. Our confidentiality agreements generally require our employees and consultants to hold in confidence and not disclose any of our proprietary information. Despite our efforts to protect our proprietary information, unauthorized parties may attempt to obtain and use our proprietary information. Policing unauthorized use of our proprietary information is difficult, and the steps we have taken might not prevent misappropriation, particularly in foreign countries where the laws may not protect our proprietary rights as fully as do the laws of the United States.
We have applied for registration of the trademarks “Increlex(TM) ,” “Tercica” and the Tercica logo in the United States.
★Competition [2006]
The biotechnology industry is intensely competitive and characterized by rapid technological progress. In each of our potential product areas, we face significant competition from large pharmaceutical, biotechnology and other companies. Most of these companies have substantially greater capital resources, research and development staffs, facilities and experience at conducting clinical trials and obtaining regulatory approvals. In addition, many of these companies have greater experience, expertise and resources in developing and commercializing products.
We cannot predict the relative competitive positions of Increlex(TM) and Somatuline(R) Autogel(R) . However, we expect that the following factors, among others, will determine our ability to compete effectively:
・ acceptance of Increlex(TM) and Somatuline(R) Autogel(R) by physicians and patients as a safe and effective treatment; ・ reimbursement adoption; ・ product price; ・ manufacturing costs; ・ the effectiveness of our and Ipsen's sales and marketing efforts; ・ storage requirements and ease of administration; ・ dosing regimen; ・ safety and efficacy; ・ prevalence and severity of side effects; and ・ competitive products.We believe that many of our competitors spend significantly more on research and development-related activities than we do. Our competitors may discover new treatments, drugs or therapies or develop existing technologies to compete with our products. Our commercial opportunities will be reduced or eliminated if these competing products are more effective, have fewer or less severe side effects, are more convenient or are less expensive than our products.
Growth hormone products compete with Increlex(TM) for the treatment of severe Primary IGFD. If Increlex(TM) receives regulatory approval for the treatment of patients with Primary IGFD, growth hormone products will also compete with Increlex(TM) for the treatment of patients in that indication. The major suppliers of commercially available growth hormone products in the United States are Genentech, Eli Lilly and Company, Teva Pharmaceutical Industries Ltd., Novo Nordisk A/S, Pfizer Inc., and Serono S.A. Investigators from a Novo Nordisk clinical trial presented data that demonstrated growth hormone was effective in a population that included children with Primary IGFD.
In addition, children with Primary IGFD may be diagnosed as having ISS. Eli Lilly and Company and Genentech have received FDA approval for their respective growth hormone products for the treatment of children with ISS in the United States, and Ipsen is seeking ISS approval for its growth hormone product in Europe. Moreover, biosimilar growth hormone products, including Omnitrope marketed by Sandoz, a division of the Novartis group, have been or may be approved in the United States and other countries. Accordingly, we expect that several growth hormone products will compete directly with Increlex(TM) for the treatment of children with Primary IGFD.
In addition, we are aware that Chiron Corporation has developed a process to manufacture rhIGF-1 using yeast expression and has intellectual property with respect to that process. We use bacterial expression, which differs from yeast expression, to manufacture Increlex(TM) .
We believe that Bristol-Meyers Squibb Company, Genentech, Merck & Co., Inc., Novo Nordisk and Pfizer Inc. have conducted research and development of orally available small molecules that cause the release of growth hormone, known as growth hormone secretagogues. We believe that Sapphire Therapeutics has licensed certain rights to Novo Nordisk's growth hormone secretagogues and is actively developing one of these compounds for use in cancer cachexia, a wasting disorder affecting some cancer patients. These products work by increasing the levels of rhIGF-1 and, if approved, could potentially compete with Increlex(TM) . It is possible that there are other products currently in development or that exist on the market that may compete directly with Increlex(TM) .
Somatuline(R) Autogel(R) . Somatuline(R) Autogel(R) is approved in Canada for the treatment of acromegaly. Together with Ipsen we are seeking regulatory approval for the same indication in the United States. In Canada, and in the United States if approved, Somatuline(R) Autogel(R) will compete directly with Sandostatin(R) LAR(R) Depot and Somavert(R) . Sandostatin(R) LAR(R) Depot is a somatostatin analogue and has the same mechanism of action as Somatuline(R) Autogel(R) . Sandostatin(R) LAR(R) Depot is indicated for long-term maintenance therapy in patients with acromegaly and in the treatment of symptoms related to carcinoid syndrome and vasoactive intestinal peptide tumors. Somavert(R) , a growth hormone antagonist, and Sandostatin(R) LAR(R) Depot are marketed by Pfizer and Novartis, respectively, in the United States and Canada. Moreover, a subset of patients with acromegaly can be treated with radiotherapy and dopaminergic agonists. These therapies are commercially available in the United States and Canada and will also compete with Somatuline(R) Autogel(R) for the treatment of patients with acromegaly.
We are aware that Ambrilia Biopharma, QLT Inc., Valera Pharmaceuticals and Camurus AB are conducting research and development programs with long acting versions of octreotide for the treatment of acromegaly. Octreotide is the generic name of the active molecule in Sandostatin(R) and Sandostatin(R) LAR(R) Depot. We are also aware that Novartis is developing pasiretide (SOM 230) and that Ipsen is developing dopastatin for the treatment of acromegaly and other hormone secreting tumors. If approved, these therapies would compete with Somatuline(R) Autogel(R) in these indications. It is possible that there are other products currently in development or that exist on the market that may compete directly with Somatuline(R) Autogel(R) .
●Tercica, Inc.[US] ●Poducts ★Increlex(TM) (mecasermin [rDNA origin] injection) ●Press Releases Tercica Reports Increlex Receives CHMP Positive Opinion for the Treatment of Severe Primary IGF-1 Deficiency[2007.5.25] Tercica Submits Marketing Authorization Application for Increlex in the European Union[2005.12.7] FDA Approves Tercica's Increlex for Short Stature Caused by Severe Primary IGF-1 Deficiency[2005.8.31] Tercica Submits New Drug Application for Increlex(TM) as a Treatment for Short Stature Caused by Primary IGF-1 Deficiency[2005.2.28] ■Investors ●Press Releases ●SEC Fikings 10-K annual report[2007.3.9]
■Teva Pharmaceutical Industries Ltd.[イスラエル]
- http://www.teva.co.il/; イスラエル本社。世界最大のジェネリック会社 年間売上(2010)$16,121 million(1兆2897億円) 、従業員数39,660 売上高の86%が、北米・欧州。 世界製薬売上第12位。 1450主成分を60ヵ国で販売。 1990年 Teva Biologics and Specialty Products (TBSP)の前身の米Gate Pharmaceuticals設立。 ～Teva Pharmaceuticals USAの子会社として1990設立。中枢神経系薬専門。2010年現社名に変更。 1996年 Teva Pharmaceuticals USA (Teva USA)に社名変更。 ～1945年 Lemmon Pharmacal Companyとして設立、1996年Lemmon社はBiocraft Laboratoriesと合併して、 1997年 Biovail Corpの開発中の持続性ジェネリック８製品販売の１０年契約 1999年 Bio-Technology General Corpとバイオシミラー開発で戦略提携 1999年08月 米Copley Pharmaceutical, Incを買収(広範囲な製品ラインを持つ。Rx,OTC) 1999年09月 Savient Pharmaceuticals Incとバイオ医薬のジェネリック版開発 2000年04月 Teva Canada Ltdの前身加Novopharm Ltdを買収。(当時カナダのジェネリック第2位) 2001年06月 Impax Laboratories, Incと12の持続性ジェネリック製剤で戦略提携。 Teve経由で販売 2003年07月 Corporation and Impax Laboratories, Inc.と Wellbutrin® SR and Zyban&ERG; (Bupropion HCl) Extended Release Tabletsのジェネリック品のANDA転換契約 2003年07月 Andrx Corporationとジェネリック経口避妊薬の開発・販売の戦略提携 2004年01月 米国Sicor Inc.買収～ジェネリック注射剤、医薬原料 $3.4 Billionで買収 ～2007年にTeva Parenteral Medicines, Incに社名変更(従業員830人) SicorがPharmacia Corp.(Pfizerの１部門)からCytosar-U (cytarabine注)と膵臓癌薬Zanosar(streptazocin)等を獲得[2003.6.6] - Teva Completes Acquisition of Sicor [2004.1.22]～ジェネリック - FTC Grants Early Termination of HSR Waiting Period on Teva Sicor Merger[2004.1.18] 2004年12月 伊Dorom(Pfizerの伊大手ジェネリック部門)買収 $93 millionで。 - Teva Closes Acquisition Of Pfizer's Italian Generic Pharmaceutical Operation - Dorom [2004.12.1] - Teva Announces Agreement To Acquire Pfizer's Italian Generic Pharmaceutical Operation [2004.8.17] 2006年01月 米IVAX Corporation買収～39ヵ国で事業、80ヵ国以上で販売。 - Teva Announces Final Results of Merger Consideration in Connection With Ivax Acquisition[2006.2.1] - Teva Completes Acquisition of Ivax [2006.1.26] - U.S. Federal Trade Commission Clears Teva/IVAX Merger; Closing Scheduled for January 26, 2006[2006.1.23] - Teva and IVAX Announce that FTC Review Process Continues on Track and Merger Closing is Expected Shortly [2006.1.10] - Teva and IVAX Decline "Public Acquirer Fundamental Change" Option for IVAX' 1.5% Convertible Senior Notes due 2025 [2006.1.3] - Teva and IVAX Sign Consent Order, Schedule Anticipated Closing Date for Merger [2005.12.23] - Teva Issues Statement Regarding Outstanding Ivax Convertible Notes [2005.12.7] - Teva and Ivax Receive European Commission Approval for Acquisition [2005.11.24] - Teva and Ivax Shareholders Approve Pending Merger [2005.10.27] - Teva/Ivax Cash and Stock Election Deadline Update[2005.10.17] - Teva and IVAX Receive FTC Request for Additional Information [2005.10.11] - Teva to Acquire Ivax for $ 7.4 Billion [2005.7.25] 2006年03月 中国Hualida Biotechnologyに資本参加 - Teva Expands Presence in China; Increases Equity Stake in Hualida Biotechnology to 60% [2006.3.30] 2006年09月 バイオ開発でProtalix Biotherapeutics Ltd.と提携 - Teva Pharmaceutical Industries Ltd. and Protalix Biotherapeutics Ltd. announce a Collaboration Agreement for the development of two Biopharmaceuticals, based on Protalix's recombinant plant cell expression technology [2006.9.26] 2006年09月 バイオ開発でProcognia (Israel) Ltdと提携 - Teva And Procognia (Israel) Ltd. Sign an Exclusive Collaboration Agreement for the Development of Biopharmaceuticals [2006.9.21] 2007年5月 Merck KGaA のジェネリック事業を買収 - Teva Comments about the acquisition of generic business of Merck KGaA [2007.5.13] 2008年01月 CoGenesys買収 - Teva to Acquire CoGenesys Acquisition Will Bolster Teva's Biotechnology Capabilities[2008.1.22] 2008年07月 Bentley Pharmaceuticals買収 - Teva Completes Acquisition of Bentley Pharmaceuticals [2008.7.23] - Teva to Acquire Bentley Pharmaceuticals [2008.3.31]～米国drug delivery business 2008年12月 イスラエル動物薬事業を売却 - Teva announces Sale of its Israeli Veterinary Business to Phibro Animal Health [2008.10.16] 2008年12月 Barr Pharmaceuticals, Inc.買収 - Teva Completes Acquisition of Barr [2008.12.23] - U.S. Federal Trade Commission Clears Teva's Acquisition of Barr [2008.12.19] - Teva and Barr Receive European Commission Approval for Acquisition [2008.12.19] - Teva Draws on $1.75 Billion Bridge Financing in Connection with Pending Barr Acquisition[2008.12.08] - Teva and Barr Provide Update on Acquisition [2008.10.27] - Teva and Barr Receive FTC Request for Additional Information [2008.9.3] - Teva to Acquire Barr [2008.7.18] 2008年09月 興和と合弁会社、興和テバ設立 - Teva and Kowa Announce Strategic Partnership to Create a Leading Generic Pharmaceutical Company in Japan[2008.9.24] - 興和、テバファーマスーティカル、ジェネリック医薬品で戦略的提携[2008.9.24] 2009年12月 興和テバが大正薬品工業買収 - Teva-KOWA Pharma to Acquire a Majority Share Interest in Taisho Pharmaceutical Industries [2009.12.24]～66.7% - 興和テバ株式会社 大正薬品工業株式会社とジェネリック医薬品で戦略的提携[2009.12.24] 2010年08月 ratiopharm-Merckle Group買収 - Teva Completes Acquisition of ratiopharm[2010.8.10]～ドイツ第２のジェネリック企業 - Teva Receives European Commission Approval for ratiopharm Acquisition [2010.8.3] - Teva Announces Agreement With Competition Bureau of Canada Regarding Proposed Merger with ratiopharm[2010.7.30] - Teva Announces Completion of $2.5 Billion of Senior Notes Offering Secures Financing for ratiopharm Acquisition [2010.6.18] - Teva Announces Pricing of $2.5 Billion of Senior Notes Secures Financing for ratiopharm Acquisition [2010.6.15] - Teva To Acquire ratiopharm [2010.3.18] 2011年01月 Corporacion Infarmasa買収 - Teva to Acquire Corporacion Infarmasa [2011.1.26]～ペルーの大手製薬 2011年01月 Theramex買収 - Teva Completes Acquisition of Theramex [2011.1.5]～Merck KGaA社の欧州女性保健薬事業会社 - Teva to Acquire Theramex, Merck KGaA's European Based Women's Health Business [2010.10.28] 2011年07月 大洋薬品買収 - Teva Completes Acquisition of Taiyo, The Third Largest Generics Company In Japan[2011.7.14] - Teva to Acquire Taiyo [2011.5.16] 2011年08月 Cephalon買収予定 - Teva and Cephalon Receive FTC Request for Additional Information[2011.6.13] - Teva to Acquire Cephalon in $6.8 Billion Transaction [2011.5.2] ●決算■パイプライン /2011.3
($ milllion) 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 備考 Net sales 16,121 13,899 11,085 9,408 8,408 5,250.4 4,798.9(+46) 3,276.4(+30.1) 2,518.6 2,077.4 1,749.9 1,282.4 ●事業別 医薬品 15,480 13,334 10,482(+18)[95%] 8,847(+13)[94%] 7,821(+66)[93%] 4,703(+10)[90%] 4,276(+48)[89%] 2,885.1(+28.8) 2,240.2 1,838 Generics and other 10,917(+17)[68%] 9,340(+21)[67%] 7,719[70%] Innovative products 3,202(+20)[20%] 2,665(+39)[19%] 1,922[17%] Copaxone/Azilect Specialty respiratory products 875(-3)[5%] 898(+15)[6%] 778[7%] ProAir (albuterol HFA) A.P.I. 641(+13)[4%] 565(-6)[4%] 603(+7)[5%] 561(-4)[6%] 587(+12)[7%] 524(+5)[10%] 501(+35)[10%] 371.5(+43.3) 259.3 219 (医薬原料) Women’s health 374(+5)[2%] 357(-)[3%] - ParaGard and Seasonique/Seasonique Lo/Plan B Biosimilars 112(+51)[1%] 74(+17)[1%] 63[1%] GCSF/HGH 動物薬他 - - - - - 23(+5)[-%] 22(+46)[1%] 19.8(+3.7) 19.1 20 ●地域別 北米 9,988(+16)[62%] 8,585(+35)[62%] 6,413(+18)[58%] 5,428(+7)[58%] 5,065(+61)[60%] 3,146(+3)[60%] 3,059(+49)[64%] 2,055(+28) 1,611 欧州 3,947(+21)[24%] 3,271(+10)[23%] 2,976(+13)[27%] 2,645
旧2,403(+18)[25%]2,206
旧2,036(+33)[24%]1,529(+23)[29%] 1,245(+45)[26%] 861(+44) 600 その他 2,186(+7)[14%] 2,043(+20)[15%] 1,696(+27)[15%] 1,335
旧1,577(+21)[17%]1,137
旧1,307(+127)[16%]575(+16)[11%] 495(+37)[10%] 360(+17) 308 営業利益 3,871 2,405 1,145 2,395 801 1,312.9 577.8 877.4 524.0 366.3 経常利益 3,646 2,203 800
旧8272,304
旧2,353664
旧7061,308.6 603.7 872.4 499.4 340.3 純利益 3,339 2,004 615
旧6351,915
旧1,952516
旧5461,072.3 331.8(-52) 691.0 410.3 278.2 148.4 116.8 研究開発費 933 802 786[7.1%] 581[6.2%] 495[5.9%] 368.9[7.0%] 338.4[7.1%] 213.5[6.5%] 165.0 107.2 取得研究開発費 18 23 1,402 - 1,295 従業員数[連結] 39,660 35,089 38,307 27,912 26,670 14,698 13,813 10,960 Copaxone 3,316(+17) 2,826(+25) 2,262(+32) 1,713(+19) 1,414(+20) 1,176(+26) 936(+30) 720(+34) 539 435 363(+47%) 247(+54%) (glatiramer)多発性硬化症*52か国で販売 米国 2,287(+19) 1,917(+39) 1,378(+26) 1,094(+19) 916(+17) 782 625(+26) - 1997.4 米国発売 欧州 1,029(+13) 909(+3) 884(+43) 619(+24) 498(+26) 394 311(+38) Azilect 318(+31) 243(+39) 175(+46) 120 - - - - - - - - [rasagiline mesylate]パーキンソン病薬;米2006.7,欧2005.6発売 ●開発品目 /2011.3.
製品 適応症 ステージ 発売目標年 オリジン 備考
x(Copaxon後継) ●経口Laquinimod [ABR-215062,TV-5600 ;スエーデンActive Biotech AB創製、世界独占権獲得、再発MS] 現在P3
他にクローン病P2；Lupus P1/2【2010】
Laquinimod is a novel once-daily, orally administered immunomodulatory compound that is being developed as a disease-modifying treatment for relapsing-remitting multiple sclerosis. In June 2004, we acquired from Active Biotech the exclusive rights to develop, register, manufacture and commercialize laquinimod worldwide, with the exception of the Nordic and Baltic countries, and in February 2010, we amended the agreement to include the distribution and marketing rights for laquinimod in the Nordic and Baltic regions. Under the agreement, we made an upfront payment to Active Biotech and will be required to make additional payments upon the achievement of various sales targets and other milestones, with maximum payments of $92 million. Active Biotech will also receive tiered double-digit royalties on sales of the product.A Phase IIb study in 306 patients demonstrated that an oral 0.6 mg dose of laquinimod, administered daily, significantly reduced MRI disease activity by a median of 60 percent versus placebo in relapsing-remitting multiple sclerosis patients. In addition, the study showed favorable effects on the reduction of annual relapse rates and the number of relapse-free patients compared with placebo. Treatment was well-tolerated, with only some transient and dosedependent increases in liver enzymes reported. Over 1,000 multiple sclerosis patients have received laquinimod in various clinical trials. Study results were published in June 2008.
Following the results of this study, and after discussions with the FDA and the EMA, we initiated a Phase III clinical program which included the ALLEGRO and the BRAVO studies. Laquinimod received "fast track" designation from the FDA in February 2009, which may allow this product to enter the market by 2012.
In December 2010, we announced the initial results of the ALLEGRO study, a pivotal, placebo-controlled global, 24-month, double-blind, Phase III study which was designed to evaluate the efficacy, safety and tolerability of laquinimod versus placebo in relapsing-remitting multiple sclerosis patients. The results demonstrated that relapsing-remitting multiple sclerosis patients treated with 0.6 mg daily oral laquinimod experienced a statistically significant reduction in annualized relapse rate compared to placebo. Additional clinical endpoints, including significant reduction in disability progression, as measured by EDSS, were also achieved. Additional analyses of the ALLEGRO study data are ongoing, and detailed results are expected to be submitted for presentation in April 2011.
BRAVO, the second Phase III study, is a pivotal, placebo-controlled, global, 24-month, double-blind, Phase III study, designed to evaluate the efficacy, safety and tolerability of laquinimod versus placebo and to provide risk-benefit data for laquinimod versus interferon beta-1a IM (Avonex®) in relapsingremitting multiple sclerosis patients. Enrollment was completed in June 2009, after more than 1,200 patients were recruited at 156 sites in the U.S., Europe, Israel and South Africa. The trial is currently ongoing, and results are expected in third quarter of 2011. Assuming a successful outcome of this trial, we would file for regulatory approval in the U.S. and the EU.
Laquinimod has demonstrated potent therapeutic efficacy in preclinical models of other autoimmune diseases such as rheumatoid arthritis, insulindependent diabetes mellitus, Guillain-BarrAm syndrome, lupus and inflammatory bowel disease. The broad profile of efficacy in animal models of inflammatory diseases suggests that laquinimod affects a specific pathway of autoimmunity. Laquinimod is currently in Phase II development for Crohn's disease, and clinical development for lupus was initiated during 2010 with two Phase I/II studies kｿ one for lupus nephritis and additional one for lupus arthritis.
【2008】
In June 2004, Teva acquired from Active Biotech the exclusive rights to develop, register, manufacture and commercialize laquinimod worldwide, with the exception of the Nordic and Baltic countries (where Active Biotech will retain all commercial rights). Laquinimod is a novel, orally bioavailable immunomodulatory compound. Teva has made an upfront payment to Active Biotech and will conduct and fund the further clinical development of laquinimod. The agreement between the two companies also calls for Teva to make payments to Active Biotech upon the achievement of various sales targets and other milestones, with maximum payments of $92 million. Active Biotech will also receive tiered double-digit royalties on sales of the product.Two global Phase III studies, Allegro and Bravo, have been initiated in centers in the U.S., Europe, and other clinical centers worldwide. The recruitment of patients for the Allegro study has begun and the recruitment for the Bravo study is planned for the second quarter of 2008. These studies have been initiated following encouraging results of two Phase II studies and after discussions with the FDA and the European Medicines Agency:
・A Phase II study performed by Active Biotech showed that laquinimod, at a dosage of 0.3 mg daily, is well-tolerated and effective in suppressing development of active MRI lesions in patients with relapsing MS. Treatment over six months with 0.3 mg of laquinimod daily resulted in a 44% decrease in MRI disease activity. Patients with disease activity at the start of the study showed a decrease of more than 50%. The study also confirmed laquinimod’s acceptable safety profile.
●Laquinimod クローン病(P2)・ループス腎炎(P2) 【2010】
・An additional Phase IIb study completed in 2006 confirmed the efficacy and favorable safety profile of laquinimod and showed significant reduction in the rate of inflammatory disease activity and a considerable reduction in the number of clinical relapses compared to placebo at a daily dose of 0.6 mg. The majority of the patients who participated in the study continued treatment with laquinimod in an extension study. The data from the extension study further confirmed and strengthened the results from the Phase IIb study.【2008】
Laquinimod is an oral new chemical entitykﾀa quinoline-3-carboxamide derivative. In addition to the efficacy that it has shown in Phase II clinical trials related to MS, laquinimod has demonstrated potent therapeutic efficacy in preclinical models of other autoimmune diseases such as rheumatoid arthritis, insulin-dependent diabetes mellitus, Guillain BarrAm Syndrome, lupus and Inflammatory Bowel Disease. The broad profile of efficacy in animal models of inflammatory diseases suggests that laquinimod affects a pivotal pathway of inflammation and autoimmunity. During 2008, Teva expects to initiate the clinical development of laquinimod for Crohn’s disease and lupus nephritis.○ ●静注custirsen (OGX-011/TV-1011) 転移性去勢耐性前立腺癌・肺癌(P3)(OncoGenex Pharmaceuticals Inc.と提携) 【2010】
In December 2009, Teva and OncoGenex entered into a global license and collaboration agreement to develop and commercialize custirsen/TV-1011/OGX-011. Custirsen is an antisense drug developed by Isis Pharmaceuticals Inc. and licensed to OncoGenex, which is designed to inhibit the production of clusterin, a protein that is associated with cancer treatment resistance. Clusterin is over-produced in several types of cancer and in response to many cancer treatments, including hormone ablation therapy, chemotherapy and radiation therapy. Custirsen was developed to increase the efficacy of chemotherapeutic drugs and may have broader market potential to treat many cancer indications and disease stages.May 19, 2011 - Teva Pharmaceutical Industries Ltd. (NASDAQ:TEVA) and OncoGenex Pharmaceuticals, Inc. (NASDAQ: OGXI) announced today that data from three studies of their investigational compound custirsen (OGX-011/TV-1011) in castrate resistant prostate cancer (CRPC) will be presented at the 47th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, June 3-7, 2011.
Custirsen is the only compound in development designed to inhibit the production of clusterin, a protein commonly over-produced in cancer cells and a potential cause of treatment resistance. Previous clinical data from the Phase II trials demonstrated that custirsen combined with docetaxel improved overall survival rates as well as durable pain palliation.
Findings from the two pre-clinical studies that will be presented demonstrate the clinical potential of custirsen combinability with anti-cancer agents in the treatment of prostate cancer. Additionally, an overview of the ongoing Phase III SYNERGY trial in metastatic castration resistant prostate cancer (mCRPC) patients will be presented. The SYNERGY trial is one of three Phase III trials initiated under a global collaboration and license agreement between Teva and OncoGenex to develop and commercialize custirsen. from Teva and OncoGenex to Present Data on Custirsen in Prostate Cancer at the 2011 ASCO Annual Meeting[2011.5.19]
x ●Albuterol Spiromax吸入剤 喘息/COPD(P3) 【2010】
Albuterol Spiromax is a dry-powder inhaler formulation of Albuterol in our novel Spiromax®device that is designed to be comparable to ProAir®HFA. Results of two recent safety and efficacy studies indicated that the safety, efficacy, pharmacokinetic and pharmacodynamic profile of Albuterol Spiromax®was comparable to that of the marketed product, ProAir®HFA MDI.x ●QNAZE™- BDP HFA Nasal点鼻薬 アレルギー性鼻炎(P3) 【2010】
QNAZE™ is a nasal aerosol corticosteroid in development for the treatment of perennial allergic rhinitis (PAR) and seasonal allergic rhinitis (SAR). Results of SAR, a Phase III study, demonstrated significantly greater symptom relief compared with placebo. The results were presented at the 2010 Annual Meeting of the American College of Allergy, Asthma & Immunology (ACAAI). In addition recent results of PAR, a Phase III study, demonstrated significantly greater relief of nasal symptoms, including runny nose, nasal congestion, nasal itching and sneezing, compared with placebo.x ●Budesonide Formoterol Spiromax吸入剤 喘息/COPD(P2) 【2010】
Budesonide Formeterol Spiromax®is designed to be comparable to Symbicort Turbohaler, delivered through Spiromax®kﾀour novel inhalationdriven multi-dose dry powder inhaler technology.▼ ●Progesterone Vaginal Ring(DR-201)(膣リング) プロゲステロン補充療法(申請中) 【2010】
Progesterone vaginal ring (DR-201) is a silicone-based, flexible ring designed to be dosed once a week for luteal supplementation of progesterone in women undergoing assisted reproductive technology treatments.▼ ●Oxybutynin Vaginal Ring(DR-3001)(膣リング) 過活動膀胱(P3完了) 【2010】
Oxybutynin vaginal ring (DR-3001) is a silicone-based, flexible ring designed to be dosed once a month to treat overactive bladder (OAB). This new and innovative delivery system for the intravaginal delivery of oxybutynin has been developed to minimize the presystemic first-pass metabolism that occurs with orally administered oxybutynin. A Phase III trial which enrolled 1,104 patients with symptoms of OAB has recently been completed. Preliminary results demonstrate statistically significant reductions for active treatment relative to placebo in total weekly incontinence episodes and average daily urinary frequency. Analysis of the results and evaluation of long-term safety information from women using the vaginal ring for up to one year is ongoing, with final results expected in 2011.▼ ●Nomac E2(SCH900121)経口剤 経口避妊薬(EMA承認勧告) (Merck & Co.と提携)contraceptive pill combining 1.5 mg of 17-beta-estradiol with 2.5 mg of nomegestrol acetate in a 24/4 monophasic regimen. 【2010】
本剤は天然エストロゲンを含有する初の単相性経口避妊薬。 独Merck KGaA子会社Laboratoire Theramex(2011.1 Tevaが買収)が創製し、2005年にOrganonにライセンス。2006年6月から２４ヵ国180他施設で4,400例3万サイクル以上のP3件試験がスタート。 NOMAC/E2は、2011年3月にFDAの審査委員会に承認されました。2011年3月、EMAのCHMP(ヒト用医薬品委員会 ) は、NOMAC/E2に関する肯定的な意見を採用した。 米国ではMerck & Co.が開発▼ ●CG-10639 (formerly Neugranin)- albumin fused GCSF皮下注 好中球減少症(P3) 【2010】
May 31, 2011 - Teva Pharmaceutical Industries Ltd. (NASDAQ:TEVA) announced today that data from studies of two investigational Granulocyte Colony Stimulating Factor (G-CSF) compounds in breast cancer patients receiving myelosuppressive chemotherapy will be presented at the 47th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, June 3-7, 2011.A Phase II/III study of CG-10639, a long-acting recombinant human albumin-human G-CSF to prevent chemotherapy-induced neutropenia, demonstrated similar outcomes to pegfilgrastim (PEGF), for both efficacy and safety measures in breast cancer patients. The primary endpoint was duration of severe neutropenia (DSN) in days during cycle one of treatment. These data showed the non-inferiority of CG-10639 (40mg and 50mg) to PEGF; a confirmatory Phase III study comparing CG-10639 40mg and PEGF 6mg is currently underway. No clinically relevant immunogenicity with CG-10639 was observed. from Teva Announces Data on Granulocyte Colony Stimulating Factor Compounds for the Prevention of Chemotherapy-Induced Neutropenia in Breast Cancer Patients [2011.5.31]
▼ ●XM22(Lipegfilgrastim) -glycoPEGylated GCSF皮下注 好中球減少症(P3) (血小板減少症治療薬)ratiopharm買収により獲得 【2010】
June 6, 2011 - Teva Pharmaceutical Industries Ltd. (NASDAQ: TEVA) announced today that lipegfilgrastim (INN; internal code - XM22) achieved its primary endpoint of reducing the duration of severe neutropenia in a Phase III study designed to evaluate the efficacy and safety of lipegfilgrastim (XM22) compared to pegfilgrastim (Amgen's Neulasta™).Lipegfilgrastim (XM22), a long acting granulocyte colony-stimulating factor (G-CSF), was added to Teva's portfolio through the acquisition of ratiopharm. It is being developed to reduce the duration of severe neutropenia in cancer patients undergoing chemotherapy. Neutropenia is a condition in which the number of white blood cells is decreased, leaving patients more susceptible to potentially life-threatening bacterial infections. from Teva Announces Successful Results of Phase III Study of Its Long-Acting G-CSF Product (Lipegfilgrastim) in Breast Cancer Patients[2011..6.6]
x ●XM17-Follitropin alfa皮下注 不妊症他(P3) (ratiopharmから獲得) 【2010】
ratiopharmの買収を通じて獲得したGonal-f (follitropin alfa)のバイオシミラー.x(済) ●StemEx(R)(Carlecortemcel-L;臍帯血由来stem cells) 血液癌P3(白血病、リンパ腫)(Gamida Cell Ltdと提携) 【2010】
Total Investment is $32.47 million; We entered into a joint venture agreement with Gamida Cell Ltd. to develop and commercialize StemEx® , a novel cell therapy product containing expanded cord blood stem/progenitor cells for the treatment of hematological malignancies in patients who cannot find a matched donor. A Phase III pivotal study, which will enroll 100 patients in the U.S., Europe and Israel, was initiated in October 2007 with enrollment scheduled to be completed in late 2011.【2008】
Suspension of human umbilical cord blood-derived, ex vivo expanded CD133+ cells in an infusion solution, composed of PBS buffer containing 1 mM EDTA and 0.5% HSA, to a fixed concentration of 2.3-3.3 x 10(exp6) cells/ml and packed in a culture bag; In February 2005, Teva signed a joint venture agreement with Gamida Cell(M.D. Anderson Cancer Center), to develop and commercialize StemEx(R). Teva committed to invest $25 million in this joint venture. StemEx(R) is a novel cell therapy product containing expanded cord blood stem/progenitor cells for the treatment of hematological malignancies in patients who cannot find a matched donor. A Phase I/II study performed by Gamida Cell in 10 patients provided encouraging results on both the efficacy and safety of the product. In 2006, the Gamida Cell-Teva joint venture obtained a special protocol assessment from the FDA for the clinical protocol of a Phase III pivotal study, which was initiated in October 2007. This study, which will enroll 100 patients in 11 sites in the U.S., Europe and Israel, is scheduled to be completed in early 2010.
In 2005, Gamida-Cell received orphan drug status from the FDA for StemEx(R) for the treatment of hematologic diseases. This status was assigned in the E.U. for the treatment of acute myeloid leukemia and for the treatment of lymphocytic leukemia. In 2009, the University of Pittsburgh joined the codevelopment with the two companies. In 2009, Orphan Drug Designation was received in the EU for the treatment of Hodgkin's lymphoma.▼ ●CT-011 転移性大腸癌(P2)/びまん性大細胞型リンパ腫(P2)(Curetech Ltd. と提携) 【2010】
We invested in CureTech Ltd. to support two Phase II clinical trials, one focused on a hematological indication, and the other on colorectal cancer.【2008】
Teva has invested $6 million in Curetech, which has developed CT-011, a humanized MAb that exerts anti-tumor activity against a wide range of solid tumors and lymphohematologic malignancies. CT-011 acts against PD-1 (Programmed Death-1), a surface receptor inducing apoptosis, allowing the extended survival and activity of tumor-reactive T cells and NK cells. Having successfully completed a Phase I study in hematological malignancy patients, Curetech is planning a Phase II study in lymphoma and a Phase I study in solid tumors. Both studies are expected to begin enrolling patients in the first half of 2008.; [参考]CT-011 Clinical Trials▼ ●NexoBrid® 火傷の傷跡(焼痂)の治療(EMA申請)(MediWound Ltdと提携) 【2010】
NexoBridN®is an innovative product developed by MediWound for the enzymatic removal of burn-injured tissue (eschar). NexoBrid®may present an alternative to surgery and lengthy non-surgical procedures. Another benefit of NexoBrid®is its selective activity, which removes only the eschar without harming viable tissue. This minimizes the need for additional skin grafting surgery and increases the potential for spontaneous healing of the burn wound. The product met the "early stopping rules" in its Phase III clinical study in the EU. A marketing authorization application was submitted to the EMA in October 2010.x ●Diapep-277 １型糖尿病(P3) (Andromeda Biotech Ltdと提携) 【2010】
We have a license agreement with respect to Diapep-277, which is currently in two Phase III clinical studies for Type I diabetes.x ●MultiGeneAngio critical limb ischemia（重症虚血肢）(P1/2) (Multi Gene Vascular Systems Ltdと提携) 【2010】
We invested in Multi Gene Vascular Systems Ltd. to support development of MGA for the treatment of critical limb ischemia. MGA is a combined cell/gene product of autologous endothelial and smooth muscle cells, which support the growth of new arteries.▼ ●PolyHeal 慢性重症負傷(EU承認、イスラエル発売) (MediWound Ltd./PolyHeal Ltdと提携) 【2010】
We have a license agreement with respect to PolyHeal's product for the treatment of chronic and "hard-to-heal" wounds. PolyHeal already received a CE Mark and the product has been launched in Israel and is expected to be launched in Europe in the near future.● 【2010】 ●TV-1102(ATL-1102 ,ISIS-107248) 再発MS P2 【2010】 【2008】
TV-1102 is a second generation antisense inhibitor of CD49d, a subunit of VLA-4 (Very Late Antigen-4) originally developed by ISIS pharmaceuticals inc (Carlsbad US) and licensed to Teva by Antisense Therapeutics Limited (Australia). ATL-1102 was originally develop at Isis Pharmaceuticals. In December 2001, Isis and Circadian Technologies formed Antisense Therapeutics, established to focus on the discovery and development of antisense therapeutics. As part of the company's formation, Antisense Therapeutics received a license to ATL-1102 and entered into a five-year antisense drug discovery and development program with Isis. In 2008, Antisense licensed ATL-1102 to Teva.VLA-4 is a clinically validated target in the treatment of MS inhibiting the trafficking of inflammatory cells to the site of inflammation . Antisense inhibition of VLA-4 has demonstrated positive effects in a number of animal models of inflammatory disease including MS (Myers et al. J Neuroimmunol 160, p12-24, 2005). ATL-1102 is complementary to nt 4288-4207 (3'UTR) of human integrin alpha 4 (ITGA4) cDNA, and thus inhibits ITGA4 expression, blocking the synthesis of CD49d, a subunit of very late antigen-4 (VLA-4). VLA-4 is known to play a part in both the onset and progression of MS, and its inhibition may prevent white blood cells from entering the central nervous system.
A Phase IIa studying the safety and efficacy of TV-1102 in RR-MS patients was completed. The study showed a significant reduction of 54.4% in cumulative number of new active lesions in patients taking TV1102 for 8 weeks, compared to placebo, as measured by magnetic resonance images (MRI). [参考]Teva & ANP Announce That ATL/TV1102, a Novel Drug for The Treatment of Relapsing Remitting Multiple Sclerosis (RRMS), Demonstrated Significant Reduction In Disease Activity[2008.6.30]
●Rasagiline Mesylate(Azilect/TV-1012) [適応追加]アルツハイマー病 P2 【2010】 【2008】
Rasagiline, the active ingredient in Azilect(R), initially showed beneficial activity in experimental models relevant to Alzheimer’s disease. Furthermore, as rasagiline’s mechanism of action is different from that of all currently approved drugs for this indication, it was believed that it had the potential of being a good candidate for combined treatment with such approved drugs. A joint cooperation of Teva and Eisai regarding rasagaline was terminated in 2006. A Phase II study initiated in 2004 by Eisai and Teva has not reached its primary endpoint, and no further development is planned at this stage.(エーザイは2003.5米国共同販売契約
契約終了2006.7.12)；本剤は第二世代の非可逆的MAO-B阻害剤としてパーキンソン病で米国発売2006.7[Teva]。●Glatiramer acetate (GA) [適応追加]ALS P1/2 【2010】 【2008】
The active ingredient of Copaxone(R) in a 40 mg/day dosage form is being developed for the treatment of ALS. The safety and tolerability of Copaxone(R) administered either daily or every alternate week has been examined in a Phase I/II study in ALS patients and has been found to be safe. In December 2006, Teva completed recruitment of 366 patients into a double-blind, placebo-controlled multicenter Phase II clinical study. This study will evaluate the safety, tolerability and efficacy of GA administered subcutaneously, once daily at a dose of 40 mg/day over one year of treatment. The primary endpoint will review the change in deterioration of the ALS functional scale. ALS is a motor neuron disease, characterized by degeneration and loss of upper and lower motor neurons. Median survival time is 3-5 years with death most often due to respiratory failure. The dosing of the last patient in the double-blind phase of the study was completed, with results expected during the second quarter of 2008.●Talampanel(GYKI-53773 , IDR-53773 ,LY-300164 ,Ampanel ,Kinampa) ALS P2 【2010】 【2008】
Ivax (Originator),Institute for Drug Research (Originator) Talampanel was initially discovered at the Institute for Drug Research in Hungary, which eventually became a wholly-owned subsidiary of Ivax. Teva acquired rights to talampanel upon acquisition of Ivax in early 2006.; Teva has exclusive worldwide rights to develop and market talampanel for the treatment of neurological disorders. Talampanel is an orally active antagonist of the alpha-amino-3-hydroxy-5- methyl-4-isoxazolepropionate (AMPA) neuronal excitatory glutamate receptor. Based on talampanel’s anti-glutamate excitatory activity, Teva believes that talampanel can significantly delay the functional deterioration of ALS patients. Based on the scientific, mechanistic rationale and a positive signal from a small Phase II study in ALS, Teva is proceeding with the development of talampanel for the latter indication, and a new Phase II study will commence during 2008. ;EUオーファン指定09.6.12 In 2008, the drug candidate received an orphan drug designation in the U.S. for the treatment of amyotrophic lateral sclerosis, and in 2009 orphan drug designation was received both in the U.S. and the EU for the treatment of glioma. Also in 2009, an additional orphan drug designation was received in the EU for the treatment of amyotrophic lateral sclerosis.●Talampanel 脳腫瘍(glioma) P2 【2010】 【2008】
Talampanel’s ability to block AMPA receptors may act against malignant gliomas, both slowing their growth and reducing their ability to invade brain tissues. An ongoing Phase II study is currently being conducted by a consortium of nine clinical centers in the U.S. with 72 patients with newly diagnosed glioblastomas being treated with talampanel as an adjuvant therapy (in addition to their standard treatment) throughout their course of chemoradiotherapy. The Phase II study is scheduled to end by the third quarter of 2008. Should this Phase II study be successful, a Phase III study is planned for 2009. ;EUオーファン指定09.4.29●Debrase 酵素性火傷病巣清掃剤 P3 【2010】 【2008】
Teva has invested $15 million in MediWound Ltd. and will jointly develop Debrase(R) with MediWound. Debrase(R) is an innovative botanical product developed by MediWound for the enzymatic removal of burn eschar (burn-injured tissue) of patients treated in burn units and hospitals. Currently, the product is in a Phase III clinical study in the EU and successfully completed a Phase II study in the U.S. Upon the successful completion of the Phase III study, a marketing authorization application is expected to be submitted to the EMEA by the end of 2008. A Phase III study in the U.S. is scheduled to start during 2009. During the clinical trials, Debrase(R) demonstrated the removal of approximately 90% of the burn-injured tissue, within four hours. Thus, Debrase(R) may present an alternative to surgery and/or lengthy non-surgical procedures which are commonly practiced today. Another benefit of Debrase(R) is its selective activity which removes only the dead burn eschar without harming the vital tissue. This enables treatment that would avoid the need for additional skin grafting surgery, while taking advantage of the potential for spontaneous healing of the burn wound (tissue-sparing effect).P3中間報告、患者エントリー完了、欧州申請は2010年内に予定。なお本剤はオーファン指定。 from Teva Comments on Positive Results of Phase III Trial in Mediwound's Debrase[2009.10.20]
●Pagoclone (CI-1043 ,IP-456 ,RP-62955 ,RP-59037 (racemate)) 吃音(どもり)(Stuttering) P2/3 【2010】 【2008】
Pagoclone is a novel member of the cyclopyrrolone class, which acts as a GABA receptor modulator and is thought to increase the action of GABA, thereby reducing excess neuronal activity and alleviating the symptoms of anxiety and panic. The compound is in phase II/III clinical studies at Indevus for the treatment of stuttering.Pagoclone had been studied for the treatment of premature ejaculation, but the development was discontinued due to insufficient efficacy.
Indevus obtained an exclusive worldwide license from RhAxne-Poulenc Rorer (now sanofi-aventis) for the manufacture, use and sale of pagoclone, with an option for marketing rights in France reverting back to Aventis. After extensive clinical and regulatory development activities, Indevus, in 1999, entered into an exclusive, worldwide license with Warner-Lambert Company (now Pfizer), for the manufacture, use and sale of pagoclone. Following reacquisition of the worldwide rights to the product from Pfizer in June 2002 where it had reached phase III clinical trials, Indevus is currently pursuing new partnerships for the development of pagoclone. In 2008, the compound was licensed to Teva by Indevus worldwide for the treatment of persistent stuttering.
●TV-3813 乾癬 前臨床 【2010】 【2008】
Topical formulation of olyel alcohol derivative : 免疫調整剤 [Molecular Target] Tumor necrosis factor (TNF) alpha●Cladribine (Mylinax(R)) MS P3(Serono S.A提携) 【2010】 【2008】
Teva is a party to an agreement with Serono S.A. for the development of a proprietary oral formulation of cladribine (Mylinax(R)) as a treatment for multiple sclerosis. Under the agreement, which was entered into by Ivax prior to its acquisition by Teva, Teva is entitled to a royalty on sales of Mylinax(R) if it is commercialized.
Cladribine cyclodextrin complex 10mg tablets and placebos are currently in Phase III trials which started in the first quarter of 2005.●経口Copaxone P2開発中止2006.3 ●TV-3606 MS P1中止 【2008】
新規化合物の経口剤。 2006年1月頃後報告がない●Edratide Acetate (TV-4710)免疫調整剤 P2開発中止 【2008】
a synthetic peptide based on the complementary-determining region 1 (CDR1) of the 16/6Id human anti-DNA antibody. This may enable specific immuno modulation of the autoimmune processes in lupus. A Phase II study designed to assess the efficacy and safety of Edratide that was completed during 2007 did not meet its primary endpoint and the project was terminated at the end of 2007. The rights to the project were returned to the Weizman Institute.● 【2010】
●Copaxone (glatiramer)多発性硬化症 【2010】
Copaxone®. In 2010, Copaxone® (glatiramer acetate injection) continued to be the leading multiple sclerosis therapy in the U.S. and globally. Global in-market sales grew by 17% over 2009, reaching $3,316 million. Price increases, partially offset by negative currency effects, accounted for less than half of the increase, and unit growth accounted for the remainder.U.S. in-market Copaxone® sales increased 19% to $2,287 million, and non-U.S. in-market sales increased by 13% to $1,029 million, compared to 2009. Growth in U.S. sales of Copaxone® was driven by price increases in January and May, of 9.9% each, and, to a lesser extent, by increases in unit sales. In January 2011, there was an additional 14.9% increase in the price of Copaxone® in the U.S. The increase in sales outside the U.S. was driven primarily by unit growth, partially offset by adverse currency effects and cost-containment measures by governments. In local currency terms, in-market sales outside the U.S. grew by 14%. Markets outside the U.S. with substantial unit growth included U.K., Italy, Germany, Spain and Russia. U.S. in market sales accounted for 69% of global Copaxone® sales in 2010, compared with 68% in 2009.
The first quarter of 2010 was the last quarter in which we made payments to Sanofi-Aventis of 25% of in-market sales in the U.S. and Canada. These payments were recorded as selling and marketing expenses. With the termination of this obligation, our selling and marketing expenses in North America after April 1, 2010 decreased accordingly.
We have an additional collaborative agreement with Sanofi-Aventis for the marketing of Copaxone® in Europe and other markets. Under the terms of this agreement, Copaxone® is co-promoted with Sanofi-Aventis in Germany, the U.K., France, Spain, the Netherlands and Belgium and is marketed solely by Sanofi-Aventis in the rest of the European markets, Australia and New Zealand. Commencing in 2009 and to a greater extent by 2012, we are gradually assuming marketing responsibilities for Copaxone® in territories covered under this additional agreement. During 2010, Teva successfully took over marketing responsibilities for Copaxone® in the U.K., the Czech Republic and Poland. Sanofi-Aventis is entitled for a period of two years to 6% of the in market sales of Copaxone® in the applicable countries. Sanofi-Aventis will also cease sharing our Copaxone® selling and marketing expenses in these markets. This change will eventually result in increases in net sales, gross profit and gross profit margin for Copaxone®; however, the effect on operating income in 2011 will be minimal.
To date, Copaxone® has been approved for marketing in 52 countries worldwide, including the U.S., Canada, Israel and all EU countries. U.S. market shares in terms of new and total prescriptions were 37.1% and 40.4% respectively, according to December 2010 IMS data.
In 2009, in-market global sales of Copaxone® amounted to $2.8 billion, an increase of 25% over 2008. U.S. sales in 2009 accounted for 68% of global sales of Copaxone®. The growth of in-market sales of Copaxone® in the U.S. in 2009 also reflected the impact of two price increases of 9.9% each.
【2010 Competition】
There are four formulations of beta-interferon which primarily compete with Copaxone®: Avonex®, Betaseron®, Extavia@� and Rebif®. Another therapy, Tysabri®, was reintroduced in the U.S. in June 2006 with a "black box" label, which includes the most critical information about Tysabri®, such as indications and warnings, and with an indication for patients who have had an inadequate response to, or are unable to tolerate, alternate multiple sclerosis therapies. In July 2006, Tysabri®was launched in the EU with a restricted indication for patients who have failed beta interferons or for highly active patients. An additional change in labeling was implemented in early 2010 by both the EMA and the FDA suggesting that the risk of PMLkﾀa fatal brain infectionkﾀincreases with the number of Tysabri®infusions.We expect that in the next few years, the multiple sclerosis treatment landscape will change with the expected launch of additional products, some of which are orally administered. The first orally administered disease-modifying therapy, fingolimod (Gilenya®), which competes with Copaxone®, was approved by the FDA in September 2010. This once-daily drug was approved for the treatment of relapsing remitting multiple sclerosis patients and included a risk evaluation and mitigation strategies (REMS) program to inform healthcare providers about the serious risks of fingolimod, including bradyarrhythmia and atrioventricular block at treatment initiation, infections, macular edema, respiratory effects, hepatic effects, and fetal risk. In January 2011, fingolimod received a positive opinion from the EU Committee for Medicinal Products for Human Use (CHMP) of the EMA for approval as a second line MS treatment.
Oral cladribine was submitted by Merck KGaA during 2009 to both the FDA and the EMA. It received a negative recommendation from the CHMP in Europe in November 2010, and is still being reviewed by the FDA with a decision expected by spring 2011. This follows the issuance in November 2009 of a "refuse to file letter" by the FDA due to an incomplete NDA submission.
In July 2008, we learned that Sandoz Inc., the U.S. generic drug division of Novartis AG, in conjunction with Momenta Pharmaceuticals, Inc., filed an ANDA with the FDA for a generic version of Copaxone®containing Paragraph IV certifications to each of our patents listed in the FDA's Orange Book for the product. In August 2008, we filed a complaint against Sandoz, Inc., Sandoz International GmbH, Novartis AG and Momenta Pharmaceuticals, Inc. in the U.S. District Court for the Southern District of New York, alleging infringement of four Orange Book patents. The patents, which expire on May 24, 2014, cover the composition of Copaxone®, pharmaceutical compositions containing it, and methods of using it. The lawsuit has triggered a stay of any FDA approval of the Sandoz ANDA, which expired in January 2011. Sandoz filed its answers to our complaint in November 2008. The answers include declaratory judgment counterclaims of non-infringement, invalidity, and unenforceability of all seven Orange Book listed patents, as well as two process patents, including a process patent that does not expire until September 2015. Our response maintaining the validity and enforceability of all of the patents-in-suit was filed in December 2008. A hearing was held in January 2010 to determine, among other claim terms, the meaning of certain terms used in the claims of Teva's Orange Book patents. Discovery is now complete. In September 2010, the Court denied Sandoz's motion for summary judgment of indefiniteness.
In September 2009, Teva learned that the FDA had accepted the filing of a second ANDA for glatiramer acetate by Mylan Inc. in collaboration with Natco Pharma Ltd. The Mylan filing alleged invalidity and non-infringement of all Orange Book patents. In October, 2009, we filed a complaint in the U.S. Court for the Southern District of NY against Mylan Pharmaceuticals, Inc., Mylan Inc. and Natco Pharma Ltd. alleging infringement of all seven Orange Book patents. Mylan's response contained declaratory judgment counterclaims of non-infringement, invalidity, and unenforceability of all seven Orange Book listed patents, as well as two process patents, including a process patent that does not expire until September 2015. We filed a response maintaining the validity and enforceability of all of the patents-in-suit. Discovery is now completed. Mylan has filed a summary judgment motion similar to that submitted by Sandoz and Momenta, which is currently pending before the court.
Recently, the Sandoz and Momenta and the Mylan and Natco patent litigations were consolidated so the cases will be tried together in the Southern District of New York. We do not yet have a trial date, but anticipate the Court will set one after it has ruled on all summary judgment motions.
Our patents on Copaxone®have been challenged, and we may face generic competition prior to 2014, when the U.S. Orange Book patents covering Copaxone®would otherwise expire.
【2008】
Copaxone(R), Teva’s largest product and its first major innovative drug, is a leading multiple sclerosis (“MS”) therapy. Copaxone(R), indicated for reduction of the frequency of relapses in patients with relapsingremitting multiple sclerosis (“RRMS”), is a class of modifying therapy with a dual mode of action that offers MS patients a different treatment concept.Multiple sclerosis is a chronic disease of the central nervous system characterized by both inflammation and neurodegeneration, which are both interrelated and independent of each other. In the majority of patients, the disease is of the relapsing-remitting form, which is manifested by acute attacks (relapses) followed by recovery (remission). This recovery may be incomplete at times, resulting in a disability progression which is measured by the Expanded Disability Status Scale (“EDSS”).
The science behind Copaxone(R) has been developed over many years, and three clinical trials (prospective, randomized and controlled) have established its efficacy and safety. The three studies include two two-year studies conducted in the U.S., which demonstrated Copaxone(R)’s efficacy in reducing relapses. The third study, conducted in Europe and Canada, also established Copaxone(R)’s efficacy in reducing inflammation as measured by the number of brain lesions, as detected through magnetic resonance imaging (“MRI”). In addition, one of the two-year studies was extended as an open-label trial to 15 yearskﾀmaking it the longest continuous study ever of patients with relapsing-remitting multiple sclerosis. Results published after the first 10 years showed that in patients who continue to inject Copaxone(R) for an average of 10 years, the number of attacks was reduced to an average of one attack every five years, and nine out of ten patients continue to be able to walk unaided. In addition, no additional safety concerns other than those reported in the pivotal studies were detected in these long-term treated patients.
Significant efforts have been made to investigate Copaxone(R)’s mode of action. The current understanding suggests that it has a dual mechanism of action both outside and within the central nervous system (where MS is active) to regulate inflammation at the site of brain lesions. In addition, it has been demonstrated in animal models as well as in MS patients using unconventional MRI techniques that Copaxone(R) controls neurodegeneration and enhances repair. Copaxone(R) reduces the number of brain lesions that evolve into permanent black holes, slows brain shrinkage and increases the production of factors that enhance neuronal repair. Recently, it has been demonstrated that Copaxone(R) slows the reduction in the concentration of the metabolite NAA (N-acetyl aspartate), a marker that is highly correlated with progression of disability in MS.
In 2004, Teva initiated a comparative trial (ACHIEVE) in which patients who are on a high dose of interferon and who experienced at least one relapse in the year prior to study entry are randomly switched to Copaxone(R) or remain on the high dose interferon for the duration of the trial. The trial is being conducted in North America, with results expected in 2009.
In 2007, results from three direct comparative studies of high dose interferon beta and Copaxone(R) sponsored by third parties were presented: the BECOME study involving 75 patients; the BEYOND study involving 2,200 patients (both sponsored by Bayer-Schering); and the REGARD study involving 764 patients (sponsored by Merck-Serono). The studies measured clinical parameters such as time to first or multiple relapses, progression on the EDSS scale and various MRI measures of disease activity. All three studies, which involved nearly 3,000 RRMS patients, were designed to demonstrate the superiority of interferon beta over Copaxone(R), and all three failed to demonstrate such superiority.
Three further studies were presented in 2007 comparing the efficacy of interferons and Copaxone(R) in controlling neurodegeneration in the short term. All three studies showed that Copaxone(R) was significantly more beneficial.
Pre-planned interim analysis of the Teva-sponsored PreCISe trial in patients presenting a first clinical event and MRI features suggestive of MS, showed that treatment with Copaxone(R) reduced the risk of developing clinically definite MS by 45% versus a placebo, and prolonged the quartile time to disease conversion. Based on these results, Teva is preparing to apply for a new indication in the U.S. and Canada and file a request for marketing authorization of Copaxone(R) in Europe for the treatment of patients with a first clinical event suggestive of MS. Finally, data suggests that Copaxone(R) is beneficial not only for mild to moderate MS patients but also for aggressive recurrently relapsing patients. Several studies published in 2006 and 2007 showed that patients with rapidly deteriorating MS who received Copaxone(R) alone following short-term induction treatment with an immunosuppressant (mitoxantrone), or following six months of combination therapy with monthly intravenous steroids, had a pronounced and sustainable reduction in relapses and MRI-measured enhancing lesions of the brain.
A large Phase III study entitled FORTE is being conducted to explore the greater efficacy of a new higher dose of Copaxone(R) (40mg/day), following positive results obtained in the Phase II study. The Phase II study showed that patients treated with the higher dose of Copaxone(R) had a 38% greater reduction in the mean cumulative number of brain lesions as measured by MRI compared with those treated with a 20 mg/day dose of Copaxone(R), with a safety profile similar to Copaxone(R) 20 mg/day.
This Phase III study compares 40mg Copaxone(R) to 20mg Copaxone(R) for 12 months in 1,150 RRMS patients. Based on consultation with the FDA and the MHRA (U.K. Medicine and Healthcare Regulatory Agency), a submission for approval of the 40 mg dose, with the same labeling as that of the 20mg dose, may be based on this one-year Phase III study, with an additional one-year open-label extension where all patients will be treated with the higher dose. This study is ongoing in 20 countries, and results are expected in the third quarter of 2008.
To date, Copaxone(R) has been approved for marketing in 51 countries worldwide, including the United States, Canada, Israel, 27 European Union countries, Switzerland, Australia, Russia, Turkey, Mexico, Brazil and Argentina. Copaxone(R) was first launched in Israel in December 1996, followed by the launch in the United States in March 1997 and European Union approval in 2001 through the European mutual recognition procedures. Teva is the licensee of pending patent applications directed to methods of treating MS by administering 40mg dosage forms of Copaxone(R). If granted, the patents would expire in 2027.
In 2007, in-market global sales of Copaxone(R) reached a new record of $1,713 million, an increase of 19% over 2006. Copaxone(R) became the leading therapy for multiple sclerosis in the U.S., in dollar terms. U.S. Copaxone(R) sales continued to increase, reaching $1,094 million, an increase of 19% compared to 2006. U.S. sales represented 64% of total in-market sales in 2007. Sales also increased in Canada. The growth of in-market sales of Copaxone(R) in the United States also reflected the impact of two price increases of 10% and 7%, announced during 2007.
In-market sales outside the U.S., primarily in Europe, increased 24% to $619 million, driven by significant sales increases in Teva’s principal European markets (the U.K., France and Germany, the largest MS market in Europe), as well as in Russia, Brazil and certain other Latin American countries. Since the exchange rate of most currencies appreciated against the U.S. dollar in 2007 (when annual average is compared to annual average), sales growth of Copaxone(R) outside the U.S. was also impacted by currency movements.
Copaxone(R) for the North American market is manufactured by Teva and supplied to Sanofi-Aventis, the distributor, at a transfer price. Teva actively markets and promotes the product in the U.S. and Canada, respectively, through a wide range of activities, including doctor detailing, educational seminars, websites and patient support programs, such as Shared Solutions(R) and MS Watch(R). Based on the current agreement with Sanofi-Aventis, Teva is expected to assume responsibility for the distribution of Copaxone(R) in the U.S. and Canada commencing April 1, 2008 and, as Teva cannot presently estimate the total amount to be paid to Sanofi- Aventis, it will thus record the full in-market sales of Copaxone(R), net of a payment to Sanofi-Aventis of 25% of the in-market sales for a period of two years. Although Teva will record higher revenues as a result of this change, it will also be responsible for certain marketing and administrative expenses, which will no longer be shared with Sanofi-Aventis. The resulting increase in expenses will substantially offset the increase in reported revenues, and therefore there will be minimal change to net income during this two-year period. Commencing April 2010, Teva will stop making this payment to Sanofi-Aventis and thereafter will record all in-market sales and profits of Copaxone(R) for the U.S. and Canada. Currently, Teva and Sanofi-Aventis are still negotiating the existing agreement to determine whether changes can be made that would be mutually beneficial.
Teva and Sanofi-Aventis have an additional collaborative agreement for the marketing of Copaxone(R) in Europe and other markets. Under the terms of this agreement, Copaxone(R) is co-promoted with Sanofi-Aventis in Germany, the U.K., France, Spain, the Netherlands and Belgium and is marketed solely by Sanofi-Aventis in the rest of the European markets, Australia and New Zealand. The product is manufactured by Teva, and Sanofi- Aventis distributes it in Europe. Commencing in 2010, but mainly as of February 2012, Teva expects to gradually take over marketing responsibilities for Copaxone(R) in territories covered under this additional agreement, at which time Sanofi-Aventis will be entitled to pre-agreed residual payments for a period of two years, following a pattern similar to that under the North America agreement described above, but with Teva making significantly lower payments to Sanofi-Aventis.
Multiple sclerosis remains an important focus of Teva’s development efforts, as Teva continues to investigate potential improvement of Copaxone(R) and explore other molecules as future therapies for MS.
【2007 競争】
Copaxone(R) is a non-interferon therapy available for the treatment of relapsing remitting multiple sclerosis. Its primary competition is with three formulations of beta-interferons, AvonexR, Betaseron(R) and Rebif(R). A fifth therapy, TysabriR, was re-introduced in the U.S. in June 2006 with a “black box” label, which includes the most critical information about TysabriR, such as indications and warnings, and with an indication for patients who have had an inadequate response to, or are unable to tolerate, alternate multiple sclerosis therapies. In July 2006, Tysabri(R) was launched in the EU with a restricted indication for patients who have failed beta interferons or for highly active patients.
Teva continues to believe that Copaxone(R) is a superior product with long-term benefits, being the only product for which efficacy and safety have been demonstrated for over 10 years in a continuous prospectively planned study.
In 2007, results from three company-sponsored, direct comparative studies between high dose interferon beta and Copaxone(R) were presented: the BECOME study involving 75 patients; the BEYOND study involving 2200 patients (both sponsored by Bayer-Schering); and the REGARD study involving 764 patients (sponsored by Merck-Serono). The studies measured clinical parameters such as time to first or multiple relapses, progression on the EDSS scale and various MRI measures of disease activity. All three studies, which involved nearly 3000 RRMS patients, were designed to demonstrate the superiority of interferon beta over Copaxone(R) but failed to show any difference in efficacy in the short term.●Azilect(R) (rasagiline mesylate) パーキンソン病 【2010】
Azilect®(rasagiline tablets), indicated for the treatment of Parkinson's disease as initial monotherapy and as an adjunct to levodopa, is our second innovative drug to be in the market. Parkinson's disease is the second most common neurodegenerative disorder, which typically occurs at an advance age, affecting approximately 1-2% of the population over the age of 65 and increasing to 3-5% in people over the age of 85. Although many symptomatic therapies are available, there is still a high level of dissatisfaction with many of these treatments, in terms of efficacy, safety and tolerability, and the major unmet need for Parkinson's disease is to slow the clinical progression of the disease.Azilect®is a potent, second-generation, irreversible monoamine oxidase type B (MAO-B) inhibitor, indicated for treating the signs and symptoms of Parkinson's disease in both early stage and in moderate to advanced stages of the disease, with a favorable tolerability and safety profile. Azilect®has also demonstrated neuroprotective and neurorestorative activities in various in vitro and in vivo models. Azilect®1mg/day is the only Parkinson's drug that has clinical data consistent with a possibility of disease modifying effect as demonstrated by slowing down the clinical progression of the disease, in addition to its symptomatic efficacy. Azilect®was launched in its first market, Israel, in March 2005, followed by a rolling launch in various European markets, and became available in the U.S. in 2006. Currently, Azilect®is approved for marketing in 45 countries and is expected to enter Australian and Asian markets over the next several years.
The development of Azilect®is part of a long-term strategic alliance with Lundbeck, which includes the global co-development and marketing of Azilect®, mainly in Europe, for the treatment of Parkinson's disease. Under the agreement, we jointly market the product with Lundbeck in certain key European countries. Lundbeck exclusively markets Azilect®in the remaining European countries and certain other international markets. In North America, Azilect®is marketed by Teva's wholly-owned subsidiary Teva Neuroscience.
During the development program, Azilect®has demonstrated efficacy and safety in four major studies that included over 2,700 patients with Parkinson's disease at different stages of the disease. Two Phase III studies (PRESTO and LARGO) demonstrated Azilect®'s efficacy as adjunctive therapy to levodopa in moderate-advanced patients. The LARGO study also showed effects comparable to the COMT inhibitor, entacapone. The TEMPO and ADAGIO studies were done in early-stage patients. In TEMPO, Azilect®demonstrated efficacy and safety as monotherapy treatment at six months, and suggested a possible effect on disease progression based on the 12-month results. An extension study showed that benefits of early treatment with Azilect®were maintained over time, for up to 6.5 years.
The ADAGIO study, one of the largest studies ever conducted in Parkinson's disease, which employed a delayed-start design and novel statistical endpoints to assess the effect of Azilect®on slowing the clinical progression of the disease in early untreated Parkinson's patients. The study results show that early treatment with Azilect®1mg/day may be consistent with a disease modifying effect by slowing down the clinical progression of the disease. These results were published in the New England Journal of Medicine in September 2009. In December 2010, based on these results, we submitted to the FDA a sNDA for the slowing of clinical progression of Parkinson's disease.
In November 2008, we announced the results of a study in which Azilect®demonstrated selective MAO-B inhibition at the approved dose of 1 mg. Non-selective MAO inhibitors may have some contra-indications with foods that contain large amounts of tyramine and certain drugs. These limitations are not associated with selective MAO inhibitors and therefore such treatments can be more broadly prescribed. Based on this study, in December 2009 the FDA approved revised prescribing information for Azilect®, reducing medication and food restrictions.
Azilect®is protected in the U.S. by several patents that will expire between 2012 and 2027. In addition, Azilect®is entitled to new chemical entity exclusivity for a period of five years from its 2006 approval date. We hold several European patents covering Azilect®that will expire between 2011 and 2014. Supplementary Protection Certificates have been granted in a number of European countries with respect to the patent expiring in 2014, thereby extending its term to 2019. Azilect®is also protected by data exclusivity protection in EU countries until 2015.
Competitive Landscape. Azilect®'s competitors include the newer non-ergot dopamine agonists class, including Mirapex®/Sifrol®(pramipexole), Requip®(ropinirole) and Neupro®(rotigotine), which are indicated for all stages of Parkinson's, as well as Comtan®, a COMT inhibitor, indicated only for adjunct therapy in moderate to advanced stages of the disease. In 2009 it was reported that the dopamine agonist Mirapex®failed to demonstrate a diseasemodifying effect in a clinical trial with a design similar to the ADAGIO trial.
In October 2010, Teva filed a complaint against Watson Pharmaceuticals, Mylan and other defendants concerning their ANDAs containing Paragraph IV certifications filed with the FDA for generic versions of Azilect®. The Teva complaint alleged infringement of Orange Book listed U.S. Patent No. 5,453,446. No trial date has been scheduled. The lawsuit has triggered a stay of any FDA approval of the ANDAs until November 2013 or a district court decision in the defendants' favor.
【2008】
Azilect(R) (rasagiline tablets) is Teva’s second significant innovative drug, indicated for the treatment of Parkinson’s disease, both as initial monotherapy in the early stage of the disease and as an adjunct to levodopa in moderate to advanced stages of the disease.Azilect(R) is a potent, second-generation, irreversible monoamine oxidase type B (MAO-B) inhibitor with neuroprotective activities demonstrated in various in vitro and in vivo studies. Its beneficial clinical effect, seen in the entire spectrum of the disease, combined with its once-daily dosing, lack of need for titration and high tolerability, allows Azilect(R) to address significant unmet needs in the treatment of Parkinson’s disease. Although many therapies are available, there is still a high level of dissatisfaction with many of these treatments, both in terms of their efficacy and tolerability. An estimated four million patients are affected by this chronic disease worldwide, which typically occurs at a late age, affecting approximately 1% of the population over the age of 65.
Teva launched Azilect(R) in its first market, Israel, in March 2005, followed by a rolling launch in various European countries, including the U.K. in June 2005 and Germany in July 2005. During July 2006, Azilect(R) became available in the U.S. As announced in July 2006, and in accordance with the termination of Teva’s alliance with Eisai, Azilect(R) is marketed in the U.S. solely by Teva, expanding its central nervous system franchise to include both Copaxone(R) and Azilect(R). To date, Azilect(R) has been made available in 29 countries, including Canada, Spain, Italy, Sweden, Belgium, Greece, Turkey, the Netherlands and Mexico. Total sales of Azilect(R) worldwide during 2007 amounted to $120 million.
The development of Azilect(R) is part of a long-term strategic alliance with Lundbeck, which includes the global co-development and marketing of Azilect(R), mainly in Europe, for the treatment of Parkinson’s disease. Under this agreement, Lundbeck and Teva jointly market the product in certain key European countries. Lundbeck will exclusively market Azilect(R) in the remaining European countries and certain other overseas markets.
Azilect(R) has demonstrated efficacy and safety in three pivotal studies that included over 1,500 patients with Parkinson’s disease at different stages of the disease. In two Phase III studies with Azilect(R) as adjunctive therapy to levodopa in more advanced patients, Azilect(R) demonstrated beneficial effects in the two categories defined as the goals for adjunctive therapy in this disease: symptomatic control of Parkinsonian symptoms and treatment of levodopa-induced motor complications.
In the TEMPO Phase III study, conducted in North America in early stage patients, Azilect(R) demonstrated efficacy and safety as monotherapy treatment, showing a highly statistically significant effect on the progression of Parkinsonian symptoms and suggesting a possible effect on disease progression based on the 12-month results of the study. In an open extension of the TEMPO trial, approximately half of the patients who were still in the study after two years (121 out of 266) were adequately maintained on monotherapy with Azilect(R) (without additional dopaminergic treatment). In this same open extension, the results of six and one-half years follow-up of patients treated with Azilect(R) show that the benefit of early treatment is maintained over time.
To date, no treatment has been proven to slow the progression of Parkinson’s disease. The pharmacological strategy for the management of Parkinson’s disease involves the use of drugs that act to increase the level of dopamine in the brain, to reduce the motor symptoms of the disease and to otherwise bring symptomatic relief to patients. However, mounting evidence suggests that early treatment administration strategy may also have the potential to impact disease progression. The rate of clinical progression is usually rapid in the early phase of Parkinson’s disease and therefore, the early period after diagnosis is critical in determining the course of disease progression and stands out as a time of opportunity for interventions aiming to modify the course of the disease.
In November 2005, Teva initiated a large, randomized, double-blind and placebo-controlled Phase IIIb clinical study to determine whether treatment with once-daily Azilect(R) can modify the progression of Parkinson’s disease, the most significant current need of patients affected by this illness. The ADAGIO study (Attenuation of Disease progression with Azilect(R) Once-daily) enrolled 1,176 patients recently diagnosed with Parkinson’s disease in North America, Europe and additional countries, including Israel and Argentina. If the ADAGIO study confirms that Azilect(R) slows Parkinson disease progression, Azilect(R) could become the first drug to be marketed with a label claim relating to modifying the progression of the disease. The results of the study are expected in mid-2008.
【2007】Canada, Spain, Italy, Sweden, Belgium, Greece, Turkey, the Netherlands and Mexico含む29ヵ国で販売。
【2007 競争】
Azilect(R) is a new treatment for early and moderate to advanced stages of Parkinson's disease. It uniquely combines a convenient once-daily, no titration dosing and favorable side effect profile, in contrast with its main competitors. Competitors include the newer non-ergot dopamine agonists class, Mirapex(R)/Sifrol(R) (pramipexole) and Requip(R) (ropinirole), which are the leading products in this class, indicated for all stages of the disease.
These products are expected to face their first generic competition in some markets in 2008, and are about to launch new once-daily slow-release formulations to replace the immediate release product currently used. An additional competitor in this class is Neupro(R), a recently launched dopamine agonist with a new once-daily patch delivery system. In the moderate to advanced stage of the disease, in addition to the dopamine agonists, Azilect(R) also competes with Comtan(R), a COM-T inhibitor.●Innovative Products 【2010】
Teva's sales of Copaxone®and Azilect®amounted to $3,202 million this year, an increase of 20% over 2009. Total global in-market sales of Copaxone®and Azilect®this year were $3,634 million, an increase of 18% over 2009.Copaxone®. In 2010, Copaxone®(glatiramer acetate injection) continued to be the leading multiple sclerosis therapy in the U.S. and globally. Global in-market sales grew by 17% over 2009, reaching $3,316 million. Price increases, partially offset by negative currency effects, accounted for less than half of the increase, and unit growth accounted for the remainder.
U.S. in-market Copaxone®sales increased 19% to $2,287 million, and non-U.S. in-market sales increased by 13% to $1,029 million, compared to 2009. Growth in U.S. sales of Copaxone®was driven by price increases in January and May, of 9.9% each, and, to a lesser extent, by increases in unit sales. In January 2011, there was an additional 14.9% increase in the price of Copaxone®in the U.S. The increase in sales outside the U.S. was driven primarily by unit growth, partially offset by adverse currency effects and cost-containment measures by governments. In local currency terms, in-market sales outside the U.S. grew by 14%. Markets outside the U.S. with substantial unit growth included U.K., Italy, Germany, Spain and Russia. U.S. in market sales accounted for 69% of global Copaxone®sales in 2010, compared with 68% in 2009.
The first quarter of 2010 was the last quarter in which we made payments to Sanofi-Aventis of 25% of in-market sales in the U.S. and Canada. These payments were recorded as selling and marketing expenses. With the termination of this obligation, our selling and marketing expenses in North America after April 1, 2010 decreased accordingly.
We have an additional collaborative agreement with Sanofi-Aventis for the marketing of Copaxone®in Europe and other markets. Under the terms of this agreement, Copaxone®is co-promoted with Sanofi-Aventis in Germany, the U.K., France, Spain, the Netherlands and Belgium and is marketed solely by Sanofi-Aventis in the rest of the European markets, Australia and New Zealand. Commencing in 2009 and to a greater extent by 2012, we are gradually assuming marketing responsibilities for Copaxone®in territories covered under this additional agreement. During 2010, Teva successfully took over marketing responsibilities for Copaxone®in the U.K., the Czech Republic and Poland. Sanofi-Aventis is entitled for a period of two years to 6% of the in market sales of Copaxone®in the applicable countries. Sanofi-Aventis will also cease sharing our Copaxone®selling and marketing expenses in these markets. This change will eventually result in increases in net sales, gross profit and gross profit margin for Copaxone®; however, the effect on operating income in 2011 will be minimal.
To date, Copaxone®has been approved for marketing in 52 countries worldwide, including the U.S., Canada, Israel and all EU countries. U.S. market shares in terms of new and total prescriptions were 37.1% and 40.4% respectively, according to December 2010 IMS data.
In 2009, in-market global sales of Copaxone®amounted to $2.8 billion, an increase of 25% over 2008. U.S. sales in 2009 accounted for 68% of global sales of Copaxone®. The growth of in-market sales of Copaxone®in the U.S. in 2009 also reflected the impact of two price increases of 9.9% each.
●Specialty Respiratory Products 【2010】
We are committed to delivering a range of respiratory products for asthma, chronic obstructive pulmonary disease (COPD) and allergic rhinitis. Our global respiratory product strategy is to extract value from both the branded and generic spheres; accordingly, our portfolio includes both branded products that utilize specific proprietary devices and pure generic products.Our principal branded respiratory products in the U.S. include ProAir®(albuterol HFA), a short-acting beta-agonist for treatment of bronchial spasms linked to asthma or COPD and exercise-induced bronchospasm, and Qvar®(beclomethasone diproprionate HFA), an inhaled corticosteroid for long-term control of chronic bronchial asthma. Qvar®is manufactured by 3M. These products are marketed directly to physicians, pharmacies, hospitals, managed healthcare organizations and government agencies. In 2010, ProAir®maintained its position as the leading rescue inhaler in the U.S., and Qvar®further advanced its second-place position in terms of new and total prescriptions in the inhaled corticosteroid market.
In Europe, our principal markets for respiratory products are the U.K., France, Germany and the Netherlands. Our main brands in these markets include Qvar®, and Airomir®(salbutamol HFA), in metered dose inhalers (MDI), as well as in breath-actuated inhalers, such as Easi-Breathe®and Autohaler®, and salbutamol HFA MDI. For patients of varying ages and disease severity who use nebulizers, we have a full range of molecules for asthma and COPD via our patented protected advanced sterile formulations Steri-Neb®(single dose plastic vial).
In the short term, we believe our current portfolio of respiratory products is well positioned to capture opportunities globally. In recent years, we have continued to build upon our experience in the development, manufacture and marketing of inhaled respiratory drugs delivered by metered-dose and dry powder inhalers, primarily for bronchial asthma and COPD. At the core of our efforts to grow our respiratory franchise globally is a continued investment in quality manufacturing capability for press and breathe metered-dose inhalers, nasal sprays and Steri-Neb®, allowing us to play an important role in all major markets and to address all of the major areas of therapeutic need.
Over the longer term, we expect to utilize our research and development capabilities, both internal and through alliances, to develop additional products based on our proprietary delivery systems, including Easi- Breathe®, an advanced breath-activated inhaler (BAI), Spiromax®/Airmax®, a multi-dose dry powder inhaler, and Steri-Neb®, the advanced sterile formulations for nebulizers. This strategy is intended to result in "device consistency", allowing physicians to choose which device matches a patient's needs both in terms of ease of use and effectiveness of delivery of the prescribed molecule for the therapeutic need. We intend to submit ten products, six of which are new brands, for approval in the U.S. and Europe by 2015.
Competitive Landscape. There are a several established global competitors who supply most of the demand to this market. There are four major MDI/ (dry powder inhaler) global brands competing with Qvar®for the mono inhaled corticosteroid segment: Flixotide/Flovent®(fluticasone) by GlaxoSmithKline, Pulmicort®(budesonide) by AstraZeneca, Asmanex®(mometasone) by Merck and Alvesco®(ciclesonide) by Nycomed, as well as four major brands that compete with ProAir®in the U.S. market for the short acting beta agonist segment: Ventolin®(salbutamol) by GlaxoSmithKline, Proventil®salbutamol) by Merck, Xopenex®(levsalbutamol) by Sunovion and Maxair®(pirbuterol) by Graceway.
Sales of our specialty respiratory products decreased 3% in 2010 to $875 million. Not included in this figure are our sales in the U.S. of budesonide, which were reported as part of our generic drug sales. Sales in the U.S. were $556 million, a 2% decline compared to 2009. ProAir (albuterol HFA) sales in the U.S. decreased by 13% from prior year, reflecting increased competition in the short-acting beta agonist (SABA) market, primarily from GlaxoSmithKline's Ventolin®HFA product. ProAir maintained its leadership in the SABA market in the U.S., with an average market share of 47.6% in terms of total number of prescriptions during the fourth quarter of 2010. Qvar®sales in the U.S. increased by 41% from prior year, with an average market share of 20.6% during the fourth quarter in terms of total prescriptions in the inhaled corticosteroid category (an increase of more than 25%).
In Europe, reduced sales of respiratory products in local currency terms in France and in the U.K. were partially offset by an increase in Germany due to the addition of ratiopharm's sales, as well as increased sales in other European countries. Sales of Qvar®increased in the principal markets in Europe as well, most notably in the U.K and Germany.
●Women's Health 【2010】
Our women's health unit manufactures and markets proprietary pharmaceutical products in the U.S. and Canada. In 2010, our women's health franchise concentrated its efforts on expanding its existing portfolio and pipeline product offerings globally, which included conducting clinical research and commercial activities for markets other than the U.S. and Canada.The current portfolio of actively promoted products in North America includes:
・Seasonique®(levonorgestrel/ethinyl estradiol and ethinyl estradiol), a 91-day extended regimen oral contraceptive;
・LoSeasonique®(levonorgestrel/ethinyl estradiol and ethinyl estradiol), a 91-day extended regimen oral contraceptive with low-dose estrogen;
・Plan B®One-Step OTC/Rx (levonorgestrel), an emergency oral contraceptive;
・ParaGard®T380 A (intrauterine copper contraceptive), a non hormonal intrauterine contraceptive; and
・Enjuvia®(synthetic conjugated estrogens, B), hormone therapy for treatment of vasomotor symptoms and vaginal atrophy.Seasonique®and LoSeasonique®represent our next-generation extended regimen oral contraceptive products. Both provide continuous hormonal support in the form of a low dose of estrogen in place of the usual seven placebo pills. Under the Seasonique®extended-cycle regimen, women take tablets of 0.15 mg levonorgestrel/0.03 mg of ethinyl estradiol for 84 consecutive days, followed by seven days of low-dose estrogen alone instead of placebo (0.01 mg of ethinyl estradiol). LoSeasonique®provides the option of a lower estrogen dose in the combination tablets and contains 0.10mg levonorgestrel/0.02mg of ethinyl estradiol to be taken for 84 consecutive days followed by seven days of estrogen alone instead of placebo (0.01mg of ethinyl estradiol).
PlanB®One-Step was approved in the U.S. in July 2009 and consists of a single tablet dose of levonorgestrel for emergency contraception. It is intended to prevent pregnancy when taken within 72 hours after unprotected intercourse or contraceptive failure. Plan B®One-Step is available over-thecounter for consumers 17 years of age and older and by prescription for women under 17.
ParaGard®intrauterine copper contraceptive provides women with a highly effective, long-term, reversible, non-hormonal contraceptive option. It is the only intrauterine contraceptive approved for up to 10 years of continuous use and is more than 99% effective at preventing pregnancy.
Enjuvia®is approved for the treatment of moderate-to-severe vasomotor symptoms associated with menopause and was the first oral estrogen to be approved by the FDA to treat moderate-to-severe vaginal dryness and pain with intercourse, symptoms of vulvar and vaginal atrophy associated with menopause. Enjuvia®uses a unique delivery system to provide slow release of estrogens over several hours.
Our women's health product development activities are focused on several categories, including oral contraceptives, intrauterine contraception, hormone therapy treatments for menopause/perimenopause, and therapies for use in infertility and urinary incontinence. Research and development is also focused on products that utilize our vaginal ring delivery platform.
In January 2011, Teva completed the acquisition of ThAmramex Labratories, a Monaco-based pharmaceutical company specializing in women's health and gynecology, as part of our efforts to expand our women's health business into key growth markets in Europe. Key products sold by ThAmramex include: Orocal®, a calcium supplement for the treatment of osteoporosis; Colpotrophine®, for the treatment of vaginal infections; Lutenyl®, for menopause; Monazol®, for fungal dermatitis; Estreva®, for estrogen deficiencies; Antadys®, for dysmenorrhea; and Leeloo GAm®, an oral contraceptive. In addition, ThAmramex has developed (in partnership with Merck & Co.) a combined oral contraceptive containing nomegestrol acetate and 17 beta-estradiol, a novel combination of an estrogen identical to the natural estrogen and a selective progestin, currently in registration in Europe.
Competitive Landscape. Our oral contraceptive products, Seasonique®and LoSeasonique®compete with Lybrel®, an oral contraceptive product based on a 365 day regimen, and generic presentations of Seasonale®that, like Seasonale®, are based on a 91 day regimen. Plan B®, our one-step emergency oral contraception product, faces competition from a generic 2-dose emergency contraception product. In December 2010, Watson launched ella®, an emergency contraceptive containing ulipristal acetate that is available only by prescription and may be taken within five days after unprotected intercourse.
Our women's health products in the U.S. reached sales of $374 million, an increase of 5% from $357 million sold in 2009. These sales figures represent proprietary women's health products only and do not include revenues from women's health products that are sold in the U.S. as generic drugs (e.g., drospirenone and ethinyl estradiol, which we market as Gianvi). Sales of ParaGard®and Seasonique®/ Seasonique Lo®increased by 18% and 63% during 2010. During the third quarter of 2009, our original two-pill dosage emergency contraception product, Plan B®, encountered generic competition and as a result its sales in 2010 declined by 32% compared to 2009. We have since refocused our marketing efforts on Plan B One-Step®, a single pill version. Plan B One Step®is currently available over-the-counter for women over the age of 17. We expect to file for full OTC status for this product in early 2011.
In 2009, sales reached $357 million, an increase of 12% from $319 million sold by Barr in 2008. Sales of all promoted products increased in 2009. These sales figures include different products than the sales reported by Barr as its overall proprietary sales.
●Biopharmaceuticals and Biosimilars 【2010】
We have identified biopharmaceuticalskﾀin particular, biosimilarskﾀas an important long-term growth opportunity. Unlike chemical (non-biological) compounds, which are produced synthetically, biopharmaceutical production involves the use of living organisms. These products, which are used to substitute disease or therapy induced deficiencies of endogenous factors, like erythropoietin or GCSF or to treat diseases like cancer, arthritis, and rare genetic disorders, make up one of the fastest-growing segments of the global pharmaceutical market and are a major contributor to increasing prescription pharmaceutical costs. According to IMS, the biopharmaceuticals market reached total global sales of over $100 billion in 2010.During the next decade, over 85% of current biopharmaceutical sales are expected to face competition from generic versions known as biosimilars, which are biological products that approximate the structure and activity of an already marketed biological entity (the "reference product"), with a target site and/or mechanism of action, if known, as described in the innovator's documentation for such reference product. In furtherance of our plans to take a leading role in the biosimilars field, we have established a dedicated research, development and manufacturing infrastructure. Our biopharmaceutical R&D facilities specialize in different technologies. Finished dosage biopharmaceutical manufacturing is carried out in our existing sterile manufacturing facilities. Our joint venture with Switzerland-based Lonza Group Ltd. provides us with access to the expertise and infrastructure of the world's largest producer of biological API. Our proprietary albumin fusion technology can be used to create long-acting biological products. In addition, as a result of the glycopegylation technology acquired through ratiopharm, we now have a second technology platform for the creation of long-acting products.
We currently market the following biosimilar products:
・Granulocyte Colony Stimulating Factor (GCSF) stimulates the production of white blood cells and is primarily used to reduce the risk of infections in oncology patients receiving chemotherapy. In September 2008, Tevagrastim®and Ratiograstim®, jointly developed by Teva and ratiopharm, became the first biosimilar GCSF to be approved in the EU. Both products were granted the entire scope of therapeutic indications for which Amgen's Neupogen®, the first GCSF product, was approved. Tevagrastim®and Ratiograstim®are now available in most European countries and will be launched in additional markets in and beyond Europe over time. Clinical trials have demonstrated that Tevagrastim®and Ratiograstim®have an efficacy and safety profile equivalent to that of Neupogen®. In December 2009, we submitted a biologic license application (BLA) for this product with the FDA, after seeking to have two Amgen patents that relate to Neupogen®declared invalid. In September 2010, the FDA issued a complete response letter to request additional information needed to complete the review of applications for product approval. This letter does not require additional pre-marketing clinical trials to complete the review of the BLA.
・Eporatio®(erythropoietin) stimulates the production of red blood cells and is indicated for the treatment of renal anemia or chemotherapyinduced anemia. In October 2009, Eporatio®was approved in the EU. Clinical trials have demonstrated that Eporatio®has an efficacy and safety profile equivalent to that of NeoRecormon®. Eporatio®is now available in several European markets, including France, Germany, Italy, Spain and the U.K. Further EU market entries are planned for 2011 and the following years. We are also evaluating filing marketing authorization applications in several countries outside the EU.
・Tev-Tropin®is a human growth hormone indicated for the treatment of children who have growth failure due to growth hormone deficiency. The current size of the growth hormone market in the U.S. exceeds $1 billion. Tev-Tropin®was launched in the U.S. in 2005 pursuant to an agreement between Teva and Savient Pharmaceuticals, Inc. In September 2009, the FDA approved a needle-free injection of Tev-Tropin®.
We are also developing several additional biosimilar products, including:
・Neugranin is a long-acting GCSF using the albumin-fusion technology initially developed by Human Genome Sciences to prolong plasma halflife. Neugranin is designed to provide clinical efficacy and safety profiles which are fully comparable to Neulasta. Neugranin is currently in Phase III clinical development.
・XM22 was added to the Teva's portfolio through the acquisition of ratiopharm. XM22 is a long-acting GCSF based on the glycopegylation technology, which ratiopharm had acquired from Neose in early 2009. Glycopegylation of GCSF leads to a prolonged plasma half-life. XM22 is designed to provide clinical efficacy and safety profiles which are fully comparable to Neulasta. XM22 is currently in Phase III clinical development.
・XM17 was added to the Teva portfolio through the acquisition of ratiopharm. XM17 is a biosimilar product to Gonal-f (follitropin alfa) for the treatment of female infertility and is currently in Phase III clinical development.
Biosimilars
During 2010, sales of biosimilar pharmaceuticals reached $112 million, as compared with $74 million in 2009 and $63 million in 2008. The increase in sales this year was mainly driven by the inclusion of ratiopharm's sales and the continued launch of our biosimilar granulocyte colony stimulating factor (GCSF) in Europe, as well as higher sales of Tev-tropin®(human growth hormone) in the U.S. More than three-quarters of the sales in 2010 were from products sold in U.S. and European markets (which beginning August 2010, also included sales of ratiopharm's products), compared to less than two-thirds in 2009.
We intend to launch additional, biopharmaceutical products over the next several years in the U.S. and in the European and International markets. During 2010 we continued launching our biosimilar GCSF under the brand name TevaGrastim in several European countries, including France, Italy, Spain, Poland and the Netherlands. In December 2009, we submitted a biologic license application for this product to the U.S. FDA. In September 2010, the U.S. FDA issued a complete response letter requesting additional information required for approval. Through the ratiopharm acquisition we added another biosimilar GCSF product, marketed as ratiograstim as well as an Epoetin theta product, sold as Eporatio, which was launched in 2010 in several European countries including Germany, France, Italy, Spain and the U.K.
●Generics 【2010】
Sales of generics and other products grew by $1,577 million, or 17%, in 2010 over 2009. Our largest market for generics is the U.S., accounting for approximately 53% of the total generics and other sales in 2010, or $5,813 million, and growing by approximately $813 million, or 16%, over 2009. U.S. benefited from approximately $1,471 million of products sold in 2010 that were not sold in 2009, as discussed above under "Sales by Geographic Area North America." In addition, the Company benefited from a full year sales of Pulmicort®(budesonide), which was relaunched in December 2009, pursuant settlement agreement with Astra Zeneca. These increases were partially offset by declines in sales of previously launched products, primarily those where had exclusive or semi-exclusive rights in 2009, such as the generic versions of Lotrel®(amlodipine benazapril), Yasmin®(drospirenone, marketed as Ocella), Protonix®(pantoprazole) and Adderall XR®(mixed amphetamine salts ER), as well as the loss of sales of injectable products manufactured in our Irvine, California facility and the absence of sales of animal health products. In addition, we had no sales in 2010 of our generic versions of Ortho Tri-Cyclen norgestimate and ethinyl estradiol, marketed as Tri-Lo Sprintec), which we launched in July 2009 and, under a settlement agreement with Ortho-McNeil Janssen Pharmaceuticals, Inc., we exited the market shortly after launch.Generics and other products from non-U.S. markets grew by $764 million, or 18%, in 2010 over 2009. This growth was enhanced by the inclusion of ratiopharm's sales and was partially offset by the impact of foreign currency exchange differences. In local currency terms, sales of generics and other products from non-U.S. markets grew by approximately 22%.
In 2009, sales of generics and other products grew by $1,621 million, or 21%, over 2008. This growth was mainly due to higher sales in the U.S., our largest market for generics, growing by $1,003 million, or 25%, over 2008. U.S. sales benefited from products sold in 2009 that were not sold in 2008, primarily due to sales of products contributed from the Barr portfolio and new product launches, partially offset by declines in both the volume and price of of previously existing products, primarily those products for which we had exclusive or semi-exclusive rights in 2008, such as Lamictal®(lamotrigine), Wellbutrin XL®(buproprion 150mg) and Risperdal®(risperidone), as well as lower sales of animal health products. Generics and other products from non- markets grew by $618 million, or 17%, in 2009 over 2008, primarily driven by the addition of Barr's European subsidiary, Pliva, and the full year impact acquisition of Bentley in 2008. This growth was partially offset by the impact of foreign currency exchange differences of approximately $490 million.
On January 31, 2011, we received a warning letter from the FDA relating to our oral solid dose manufacturing facility in Jerusalem. The letter cites cGMP deficiencies related to laboratory reporting and systems. We believe that we have addressed the FDA's observations and we are working diligently to resolve any outstanding FDA concerns. The letter does not restrict production or shipment of the products from our facility. However, unless and until we are able to correct outstanding issues to the FDA's satisfaction, the FDA may withhold approval of pending drug applications listing the Jerusalem facility. The FDA may also withhold permission to export products manufactured at the facility to the U.S.
● 【2010】
●Teva Pharmaceutical Industries Ltd.[イスラエル] - http://www.teva.co.il/ 1450主成分を60ヵ国で販売。 ■Our Products ●Branded Products ●Generic Products ●Product Pipeline ●News Teva Completes Acquisition of Taiyo, The Third Largest Generics Company In Japan[2011.7.14] Teva to Acquire Taiyo [2011.5.16] Teva and Cephalon Receive FTC Request for Additional Information[2011.6.13] Teva to Acquire Cephalon in $6.8 Billion Transaction [2011.5.2] Teva to Acquire Corporacion Infarmasa [2011.1.26]～ペルーの大手製薬 Teva Completes Acquisition of Theramex [2011.1.5]～Merck KGaA社の欧州女性保健薬事業会社 Teva to Acquire Theramex, Merck KGaA's European Based Women's Health Business [2010.10.28] Teva Completes Acquisition of ratiopharm[2010.8.10]～ドイツ第２のジェネリック企業 Teva Receives European Commission Approval for ratiopharm Acquisition [2010.8.3] Teva Announces Agreement With Competition Bureau of Canada Regarding Proposed Merger with ratiopharm[2010.7.30] Teva Announces Completion of $2.5 Billion of Senior Notes Offering Secures Financing for ratiopharm Acquisition [2010.6.18] Teva Announces Pricing of $2.5 Billion of Senior Notes Secures Financing for ratiopharm Acquisition [2010.6.15] Teva To Acquire ratiopharm [2010.3.18] Teva-KOWA Pharma to Acquire a Majority Share Interest in Taisho Pharmaceutical Industries [2009.12.24]～66.7% Teva and Kowa Announce Strategic Partnership to Create a Leading Generic Pharmaceutical Company in Japan[2008.9.24] Teva announces Sale of its Israeli Veterinary Business to Phibro Animal Health [2008.10.16] Teva Completes Acquisition of Barr [2008.12.23] U.S. Federal Trade Commission Clears Teva's Acquisition of Barr [2008.12.19] Teva and Barr Receive European Commission Approval for Acquisition [2008.12.19] Teva Draws on $1.75 Billion Bridge Financing in Connection with Pending Barr Acquisition[2008.12.08] Teva and Barr Provide Update on Acquisition [2008.10.27] Teva and Barr Receive FTC Request for Additional Information [2008.9.3] Teva to Acquire Barr [2008.7.18] Teva Completes Acquisition of Bentley Pharmaceuticals [2008.7.23] Teva to Acquire Bentley Pharmaceuticals [2008.3.31]～米国drug delivery business Teva to Acquire CoGenesys Acquisition Will Bolster Teva's Biotechnology Capabilities[2008.1.22] Teva Comments about the acquisition of generic business of Merck KGaA [2007.5.13] Teva Pharmaceutical Industries Ltd. and Protalix Biotherapeutics Ltd. announce a Collaboration Agreement for the development of two Biopharmaceuticals, based on Protalix's recombinant plant cell expression technology [2006.9.26] Teva And Procognia (Israel) Ltd. Sign an Exclusive Collaboration Agreement for the Development of Biopharmaceuticals [2006.9.21] Teva Expands Presence in China; Increases Equity Stake in Hualida Biotechnology to 60% [2006.3.30] Teva Announces Final Results of Merger Consideration in Connection With Ivax Acquisition[2006.2.1] Teva Completes Acquisition of Ivax [2006.1.26] U.S. Federal Trade Commission Clears Teva/IVAX Merger; Closing Scheduled for January 26, 2006[2006.1.23] Teva and IVAX Announce that FTC Review Process Continues on Track and Merger Closing is Expected Shortly [2006.1.10] Teva and IVAX Decline "Public Acquirer Fundamental Change" Option for IVAX' 1.5% Convertible Senior Notes due 2025 [2006.1.3] Teva and IVAX Sign Consent Order, Schedule Anticipated Closing Date for Merger [2005.12.23] Teva Issues Statement Regarding Outstanding Ivax Convertible Notes [2005.12.7] Teva and Ivax Receive European Commission Approval for Acquisition [2005.11.24] Teva and Ivax Shareholders Approve Pending Merger [2005.10.27] Teva/Ivax Cash and Stock Election Deadline Update[2005.10.17] Teva and IVAX Receive FTC Request for Additional Information [2005.10.11] Teva to Acquire Ivax for $ 7.4 Billion [2005.7.25] Teva Closes Acquisition Of Pfizer's Italian Generic Pharmaceutical Operation - Dorom [2004.12.1] Teva Announces Agreement To Acquire Pfizer's Italian Generic Pharmaceutical Operation [2004.8.17] Teva Completes Acquisition of Sicor [2004.1.22]～ジェネリック FTC Grants Early Termination of HSR Waiting Period on Teva Sicor Merger[2004.1.18] Teva Will Be Sole Promoter of Azilect(R) for Parkinson's Disease in the United States[2006.7.12] - 2003.5, 米国でAZILECT(R) (rasagiline tablets) のco-promotion契約をエーザイと 締結していたが、今回解消した。 この結果Teva Neuroscience, Inc.が単独販売する。尚本剤は2006.5.17 FDA承認され 今月末発売予定。 Teva Announces FDA Grants Approval of Azilect(R) (Rasagiline) for Parkinson's Disease[2006.5.17] -FDA承認。適応症はtreatment for Parkinson's disease both as initial monotherapy in early Parkinson's disease patients and as adjunct therapy to levodopa in mod erate-to-advanced stages of the disease。 １日１回投与は大きなメリット。 Teva Announces that Higher Dose of Copaxone? Showed Increased Efficacy in Multiple Sclerosis (Ms)[2006.4.6] Teva And Active Biotech Announce The Submission Of An Ind To The Fda For Laquinimod, An Oral Product For The Treatment Of Relapsing Ms[2005.6.28] Teva And Lundbeck Announce That Azilect (Rasagiline) For Parkinson's Disease Is Now Available In The United Kingdom[2005.6.27] Teva and Lundbeck Announce European Approval for AZILECT(R) (rasagiline) 1mg for Parkinson's Disease[2005.2.22] Teva and Lundbeck announce that Azilect(R) (rasagiline) for Parkinson's disease is recommended for approval in the EU[2004.11.18] Teva Receives Approvable Letter For Agilect(R) (Rasagiline)[2004.7.5] Teva And Aventis Announce That Copaxone(R) Pre-Filled Syringe Is Now Available Also In Europe[2004.6.17] ●Financial Reports Annual Report Form 2010 20-F[2011..2.15] - [pdf,322p] Annual Report Form 2009 20-F Annual Report 2008 Form 20F[pdf,345p] Annual Report 2007 Form 20F[pdf,169p] Annual Report 2006 Form 20F[pdf,p] Annual Report 2005 Form 20F[pdf,269p] Annual Report 2004 Form 20F[pdf,167p] Annual Report 2003 Form 20F[pdf,156p] ●Copaxone[多発性硬化症薬] Copaxone(R), Teva's leading product and its first major innovative drug, is now the leading multiple sclerosis (“MS”) therapy in the United States in terms of total prescriptions as well as new prescriptions. Copaxone(R), which is indicated for the reduction of relapse rate in patients with relapsing-remitting MS, is a new class of modifying therapy with a dual mode of action that offers MS patients a different treatment concept. Multiple sclerosis is a chronic disease of the central nervous system characterized by both inflammation and neurodegeneration, which are interrelated but are also independent of each other. Copaxone(R) effectively addresses both MS pathologies via its unique dual mode of action. Copaxone(R) regulates inflammation as shown by the significant reduction of relapses in the short term and the reduction in disease activity, as monitored by magnetic resonance imaging (“MRI”). Copaxone(R) also controls neurodegeneration, as demonstrated by: (1) reduction of 50% in the evolution of new lesions into permanent “black holes” (permanent MS lesions in the brain), which represent areas where the most severe and irreversible brain tissue damage has occurred (Neurology 2001); (2) significant reduction in the rate of brain atrophy (Neurology 2004); (3) significant reduction of axonal damage, as demonstrated by magnetic resonance spectroscopy, a technique which looks at the integrity of neuron function (Multiple Sclerosis 2005); and (4) significant secretion of a brain-derived neurotrophic factor, BDNF, which helps to protect the brain from axonal loss (Brain 2002, J Neurological Sciences 2003). Furthermore, Copaxone(R) has demonstrated sustained efficacy over 10 years, the longest term of any of the current MS therapies. MS patients followed up since the beginning of the U.S. Phase III pivotal study, taking Copaxone(R) for over 10 years, experienced on the average a relapse rate of approximately one every five years, while physical function was maintained in the majority of patients. An additional study which followed a group of patients using Copaxone(R) since it was approved in the U.S. for compassionate use in 1978 has shown that of the 18 patients still injecting Copaxone(R) daily (now for an average of 17 years), only 26.7% progressed to EDSS of 6 or more (requiring aid to walk) (Miller et. al. ECTRIMS 2005). To date, Copaxone(R) has been approved for marketing in 44 countries worldwide, including the United States, Mexico, Israel, Canada, 22 European Union countries, Switzerland, Australia, Russia, Brazil and Argentina. Copaxone(R) was first launched in Israel in December 1996, followed by the launch in the United States in March 1997, and European approval in 2001 through the European mutual recognition procedures. In 2005, in-market global sales of Copaxone(R) reached a new record of $1,176 million, of which $782 million were in the United States, where Copaxone(R) continued to strengthen its position as the market leader, according to current IMS data, reaching highs of 34.3% in terms of total prescriptions and 35.2% in terms of new prescriptions in December 2005. Global in-market sales of Copaxone(R) in 2005 grew by 26% over those of 2004, a rate of growth that almost double the growth of the global market of MS products. Outside the United States, Copaxone(R) in-market sales reached $394 million in 2005, an increase of 27%, driven by significant sales increases in Germany, the largest MS market in Europe, as well as in France, Spain and the U.K. In North America, Copaxone(R) is marketed through Teva Neuroscience and is distributed by Sanofi-Aventis. Teva manufactures the product and supplies it to Sanofi-Aventis. Teva Neuroscience Inc. and Teva Neuroscience G.P.-S.E.N.C, wholly owned subsidiaries of Teva, actively market and promote the product in the United States and Canada, respectively, through a wide range of activities, including doctor detailing, educational seminars, websites and patient support programs, such as Shared Solutions. and MS Watch.. The agreement with Sanofi- Aventis terminates in March 2008, at which point Teva expects to take over U.S. distribution responsibilities for Copaxone(R) in exchange for payment by Teva of previously agreed-upon consideration to Sanofi-Aventis. Teva and Sanofi-Aventis have an additional collaborative arrangement for the marketing of Copaxone(R) in Europe and other markets. Under the terms of this arrangement, following approval in these markets, Copaxone(R) is either co-promoted with Teva or is marketed solely by Sanofi-Aventis. The product is manufactured by Teva, and Sanofi-Aventis purchases it from Teva and sells and distributes it in Europe. Teva expects to take over European distribution responsibilities for Copaxone(R) when the agreement with Sanofi-Aventis terminates in February 2012, at which time Sanofi-Aventis will be entitled to pre-agreed residual payments. Teva is seeking to develop effective and more convenient therapies for MS. An oral formulation of Copaxone(R) was tested in a large clinical trial, CORAL, conducted from 2000 to 2002; however, the results of the trial were not statistically significant. In late 2004, Teva and H. Lundbeck A/S, a Denmark-based, publicly traded pharmaceutical company and Teva's strategic partner in the development of oral Copaxone(R), initiated two pilot Phase II clinical studies with two doses of an enteric coated formulation of Copaxone(R). Based on the results, received in March 2006, Teva and Lundbeck will not continue the development of this formulation. Nevertheless, Teva is considering future development of Copaxone(R) in various non-parenteral formulations and will make its decision in the context of its entire MS portfolio.
●Teva Pharmaceuticals Industries Ltd - http://www.tevapharm.com/ ; ●Financial Information ●News & PR ●Copaxone
●Teva Pharmaceuticals USA - http://www.tevausa.com/ ジェネリックメーカー ジェネリック製品400品目、1400規格を販売。 1945年 Lemmon Pharmacal Companyとして設立 1996年 Lemmon社はBiocraft Laboratoriesと合併して、社名をTeva Pharmaceuticals USA (Teva USA).に変更。 ●Products ★All Brand Products～40製品 Copaxone(glatiramer acetate injection)多発性硬化症 ★All Generic Products ★Teva_Product_Catalog ●News & Events ■米国ブランド製品 42製品 ～以下は別表掲載を除いた。
■Teva Respiratory, LLC 次の２製品の販売。 旧Ivax製品
選択 領域 製品名(主成分) 適応症(薬効) 競合 備考 x 循環器 Adipep-P(phentermine HCl) 肥満症 日本未導入だが、Fen-Phen問題等安全性から日本では無理 ジェネリック x 神経系 Teva Clozapine(clozapine tablets USP) 統合失調症 クロザリル錠[ノバルティス]日本導入済み ジェネリック x 代謝 Cyclosporine USP Modified(Cyclosporine Soft gelatin capsules) 臓器移植拒絶反応抑制、関節リウマチ、乾癬 ジェネリック x 代謝 Galzin(zinc acetate) ウイルソン病薬 日本導入済み x 循環器 Lofibra(fenofibrate) 脂質異常症 日本導入済み 日本導入済み x 神経系 Orap(pimozide) Tourette Syndrome (チック障害) オーラップ細粒・錠[アステラス]統合失調症、小児の自閉性障害、精神遅滞に伴う症状 x 代謝 Proglycem(diazoxide,USP)内用液剤 高インスリン血性低血糖症 アログリセムカプセル25mg[ＭＳＤ株式会社] 日本導入済み x 癌 Purinethol(6-MP;Mercaptopurine) 急性白血病薬 ロイケリン散10％[大原薬品工業] 2003.7 GSKから北米ライセンス取得 x 代謝 Tev-Tropin(somatropin(rDNA origin)) ヒト成長ホルモン 日本導入済み Savient社から導入(2002) ■Teva Neuroscience, Inc 次の２製品の販売。
選択 領域 製品名(主成分) 適応症(薬効) 競合 備考 x 呼吸器 ProAir® HFA (albuterol sulfate) Inhalation Aerosol 気管支喘息他 サルタノールインヘラー[GSK]他多数 ジェネリック x 呼吸器 QVAR®(beclomethasone dipropionate HFA, 40 mcg) 気管支喘息 キュバール[大日本住友製薬/ＭＳＤ株式会社] ■Teva Women's Health, Inc 次の5製品の販売。 子会社Barrの子会社Duramed Pharmaceuticals, Incの製品
選択 領域 製品名(主成分) 適応症(薬効) 競合 備考 x 神経系 COPAXONE(glatiramer acetate injection) 多発性硬化症 日本のテバで開発中 x 神経系 AZILECT(rasagiline tablets) パーキンソン病薬 日本のテバで開発中？ ■Teva Biopharmaceuticals USA (TBU)[旧CoGenesys, Inc]
選択 領域 製品名(主成分) 適応症(薬効) 競合 備考 x 女性保健 Plan B OneStep®(levonorgestrel 1.5mg)錠 緊急避妊薬OTC(72h以内) ノルレボ錠0.75mg[あすか製薬] 米承認1982 ○ 女性保健 Seasonique®(84錠x(levonorgestrel0.15mg/EE 0.03mg) and 7錠(EE 0.01mg Tablets))84/7EE 経口避妊薬(１日１錠91日間) 米承認1982 ○ 女性保健 LoSEASONIQUE®(84錠x(levonorgestrel 0.1mg/EE 0.02mg) and 7錠(EE 0.01mg Tablets))84/7EE 経口避妊薬(１日１錠91日間) 米承認1982 ▼ 女性保健 ParaGard®(intrauterine copper contraceptive) 銅付加子宮内避妊具(IUD) ノバT380 ○ 女性保健 ENJUVIA®(synthetic conjugated estrogens,B)Tablets 更年期障害 プレマリン 合成
選択 領域 製品名(主成分) 適応症(薬効) 競合 備考 ○ 血液 Neugranin™(recombinant human albumin-human G-CSF;CG-10639) 化学療法に伴う熱性好中球減少症 第３相 ▼ 神経系 Albuferon™ Beta(Albumin interferon beta) 多発性硬化症 前臨床 Human Genome Sciences創製
選択 領域 製品名(主成分) 適応症(薬効) 競合 備考 ()
■Barr Laboratories, Inc
Barr Pharmaceuticals Inc.の子会社、米国。 同じ子会社として、Duramed Pharmaceuticals, Inc.(銘柄医薬品の開発・製造・販売) 医薬品100製品(癌、女性保健薬、循環器、感染症、向精神薬。) 従業員数1,900人。 2001.10 Duramed Pharmaceuticals, Inc.を買収(そのまま存続)。 2004.02 Women's Capital Corporationを買収。 (Plan B) 2004.3 Galen (Chemicals) LimitedからLoestrinの製造・米国販売権を取得。 2004.11&12 King Pharmaceuticals からPrefest and Nordetteの米国独占権を取得。各$15,000 and $12,000 2005.6.15 MircetteをOrganon and Savient Pharmaceuticals, Inc.からNDAを買収。 (BarrはジェネリックKariva(R)を販売し、訴訟問題が発生していた) 2005.11 FEI Women's Health, LLCを買収($289.7 million) (10年間迄使用可のParaGard(R) T 380A (Intrauterine Copper Contraceptive) IUD) 2006.10.24 PLIVA d.d.(Zagreb, Croatia)の買収完了。($2.4 billion) ●会社決算 [決算期６月]従業員数(2007) のうちPliva 5,100、他の米国外2,650人 ●製品売上 [決算期６月]
($ 000) 2007/1-12 2006/7-12 2006/6 2005/6 2004/6 2003/6 2002/6 2001/6 備考 総収入 2,500,582 904,764 1,314,465 1,047,399 1,309,088 902,864 1,188,984 593,151 営業利益 312,645 (211,020) 522,948 329,876 194,440 262,715 337,537 101,793 純利益 128,350 (338,155) 336,477 214,988 123,103 167,566 210,269 62,566 研究開発費 248,453 106,758 140,200 128,384 168,995 91,207 ? ? 従業員数 8,900 2,040 1,900 1,480 1,224 ? ? * tamoxifen ... 2003年前半までAstraZenecaから購入。 * ciprofloxacin ... 小児用製剤のBayerからの独占販売権契約が2004.6.9に終了 ★[2006/6期メモ] ・Proprietary製品総合 the ParaGard IUD …2005.11取得 the Mircette oral contraceptive …2005.12取得 ENJUVIA(synthetic conjugated estrogens, B) …2006.5 発売 Plan B emergency contraceptive product …higher volume and pricing Loestrin/Loestrin FE oral contraceptive products and our Cenestin …低調 ・Seasonale --- $100m突破。しかし 2004.6 ANDA申請有り、2006.5 tentative FDA approval取得。 2006.9.5 先発権失効と共に最終承認見込み。 当社は2006.7 市民誓願を提出した がPending。 ●銘柄医薬品一覧(19製品) /2006/6 ★重点品目/7/ ・Advicor(R) (Niacin Extended-Release/Lovastatin Tablets) for high cholesterol (marketed under agreement with Kos Pharmaceuticals, Inc.) ・ENJUVIA^(TM) (Synthetic Conjugated Estrogens, B) hormone therapy ・Mircette(R) (Desogestrel and Ethinyl Estradiol) oral contraceptive ・Niaspan(R) (Niacin Extended-Release Tablets) for high cholesterol (marketed under agreement with Kos Pharmaceuticals, Inc.) ・ParaGard(R) T 380A (Intrauterine Copper Contraceptive) IUD ・Plan B(R) (Levonorgestrel) emergency oral contraceptive - 2004.3 Women's Capital Corp買収とともに獲得; 2006.8 OTC承認 ・SEASONIQUE^(TM) (Levonorgestrel/Ethinyl Estradiol and Ethinyl Estradiol) extended-cycle oral contraceptive - 新世代製品。 FDA承認2006.5 ★非重点品目/12/ ・Aygestin(R) (Norethindrone Acetate) for amenorrhea ・Cenestin(R) (Synthetic Conjugated Estrogens, A) hormone therapy ・Diamox(R) Sequels(R) (Acetazolamide) for glaucoma ・Loestrin(R)/Loestrin(R) Fe (Norethindrone Acetate and Ethinyl Estradiol) oral contraceptives - 2004.3 Galen (Chemicals) Limited から買収 ・Nordette(R) (Levonorgestrel and Ethinyl Estradiol) oral contraceptive - 2004.11 King Pharmaceuticals, Incから獲得 ・Prefest(R) (Etradiol/Nogestimate) hormone therapy - 2004.12 King Pharmaceuticals, Incから獲得 ・Revia(R) (Naltrexone Hydrochloride) for alcohol dependence ・SEASONALE(R) (Levonorgestrel and Ethinyl Estradiol) extended-cycle oral contraceptive ・Trexall(TM)(Methotrexate) for rheumatoid arthritis ・ViaSpan(R) (Cold Storage Solution) transplant preservation agent ・Zebeta(R) (Bisprolol Fumarate) for hypertension ・Ziac(R) (Bisoprolol Fumarate and Hydrochlorothiazide) for hypertension ★Barr製品と先発品一覧[2005.6]
($ milllion) 2007/1-12 2006/1-12 2006/6 2005/6 2004/6 2003/6 2002/6 備考 tamoxifen - - 120.9 366.3 [] ciprofloxacin* - 385.3(+246) 111.4 - (2003.6.9発売) oral contraceptives 459.1 444.0 399.4(+1) 396.6(-2) 403.9(+47) 274.4(+196) 92.8 []経口避妊薬 他のジエネリック 1,436.7 608.9 439.4(+24) 354.8(-2) 361.4(+7) 338.9 ? ジェネリック製品 1,895.8 1,052.9 838.9(+12) 751.4(-35) 1150.6 894.9 1200 Proprietary製品 438.3 391.4 329.8(+18) 278.8(+91) 146.1(+153) 57.7 - うち Cenestin - - 47.1(+36) 34.6 41.5 [合成Conjugated Estrogens] うち Seasonale 49.6 75 100(+14) 87.2 25 ? ? (levonorgestrel/EE) 製品売上高 2,334.136 1,444.3 1,168.6(+13) 1,030.2(-21) 1,296.7 提携収入 121.858 131.3 144.682 他の収入 44.588 7.5 -
旧145.8(+748)17.2(+39) 12.4(+55) 8.0 - 総収入 2,500.582 1,583.1 1,314.4(+25) 1,047.4(-20) 1,309.1 902.9 1200 ★Barrが特許切れ先発品の開発予定一覧[2007.3.1]
Barr Label 先発品 薬効分野 Apri(R)
(Desogestrel and Ethinyl Estradiol)Desogen(R)
Ortho-Cept(R)Female Healthcare Aviane(R)
(Levonorgestrel and Ethinyl Estradiol)Alesse(R) Female Healthcare Claravis(TM)
(Isotrentinoin)Accutane(R)
(Roche)Dermatology Amphetamine Salts Combination Adderall(R) Psychotherapeutics Dextroamphetamine Sulfate
Extended Release CapsulesDexedrine(R) Spansule(R) Psychotherapeutics Didanosine Delayed-Release Capsules Videx(R) EC Antiviral Kariva(R)
(Desogestrel and Ethinyl Estradiol)Mircette(R)
(Organon/ Savient Pharmaceuticals)Female Healthcare Lessina(R)
(Levonorgestrel and Ethinyl Estradiol)Levlite(R) Female Healthcare Methotrexate Rheumatrex(R) Rheumatology Metformin HCl Extended Release Tablets Glucophage(R) XL Diabetes Mirtazapine Orally Disintegrating Tablets Remeron(R) Soltabs(R) Psychotherapeutics Nortrel(R) 7/7/7
(Norethindrone and Ethinyl Estradiol)Ortho-Novum(R) 7/7/7 Female Healthcare Sprintec(R)
(Norgestimate and Ethinyl Estradiol)Ortho-Cyclen(R) Female Healthcare Tri-Sprintec(R)
(Norgestimate and Ethinyl Estradiol)Ortho Tri-Cyclen(R) Female Healthcare Warfarin Sodium Coumadin(R) Cardiovascular * Source: IMS Health ? twelve months sales ended December 31, 2006. ★Barrが特許切れ先発品の開発予定一覧[2005.6]
製品 銘柄品米国売上高
($ millions)*備考 Alendronate Sodium (Fosamax®) 1,909.0 Drospirenone and Ethinyl Estradiol (YASMIN®) 552.2 Fexofenadine (Allegra® Tablets, Allegra D®) 1,331.1 Fluoxetine HCl (Prozac® Weekly™) 30.7 Galantamine Hydrobromide Tablets (RAZADYNE®) 150.7 Galantamine Hydrobromide Extended-Release Capsules(RAZADYNE® ER) 83.7 Norgestimate/EE (TRI-CYCLEN LO®) 403.7 Olanzapine ODT (ZYPREXA® Zydis®ODT) 246.4 Oxandrolone Tablets (Oxandrin®) 58.7 Pramipexole Dihydrochloride (MIRAPEX®) 291.0 Raloxifene Hydrochloride (EVISTA®) 685.7 Thalidomide (Thalomid®) 415.6 Topiramate Capsules (Topamax® Sprinkle Capsules) 43.7 Tramadol HCl & Acetaminophen (ULTRACET®) 135.9 Triamcinolone Acetonide (NASACORT® AQ) 345.9 Total 6,684.0 *売上高は2005.6期の年間売上高(IMS) ★2005年度決算 ・ジェネリック製品は、７５製品(うち経口避妊薬２２) 銘柄製品は、主に女性向け製品の１３製品を製造販売。SEASONALE,Canestin,Plan B が主力。 ・経口避妊薬．．．競争による価格下落により売上微減。 2004年度新製品は好調、2005年度２製品発売でジェネリックOC計22製剤。 2004.7 Aranelle (norethindrone and ethinyl estradiol); Tri-Norinyl(Watson)のGE品。 2005.5 Kelnor (ethynodiol diacetate and ethinyl estradiol)；Demulen 1/35-28(Pfizer)のゾロ。 また銘柄OCとしてNordette(levonorgestrel acetate and ethinyl estradiol)の米国 独占権を2004.12にKing Pharmaceuticals, Incから獲得。 Seasonale(FDA承認=2003.9;発売2003.11)はIMSデータでは2005.6期に年80万枚の処方箋が書かれ、前年比+370%。 OC市場は2005.6期の年間$3.8 billion規模、うちBarrがシェア31%。 ★Chaiman's Letter 2003(4-5p) ・乳癌治療薬Tamoxifenは、Barr社は2003.2契約満了迄AstraZeneca社とNolvadex販売契約 を結んでいたが、2003.2に特許切れに伴い、我々は自社品を発売。 ・抗うつ剤は2002.1に我が社の独占権満了に伴い、他社ジェネリック品出現により、我が社売上は減少。 ・Fortune誌 ランク1000入り。 ・Wall Street Journal誌 1000 10-Year Best Performersでトップ10入り。 ※新製品開発 新薬とジェネリック品双方を対象。 $91.2 million (+20%;2002年$75.7 million) 臨床試験に費用がかかっている。 経口避妊薬 DP3 extended cycle oral contraceptive Trimegestone (TMG) (P2) -開発権をWyethから取得 他にvaginal ring products ※ジェネリック品 2003年度に16製品の認可取得、10製品を発売(うち経口避妊薬５)。 14製品を申請し、FDA承認待ちは３０製品以上となった。 ※特許 Additional Patent Challenges 2003年期で、５製品の特許にチャレンジした。 閉経後骨粗鬆症薬 Eli Lilly's Evista(R) コレステロール低下剤持続錠 Kos Pharmaceutical'sNiaspan(R) 500 mg and 750 mg 抗利尿剤 Ferring's patent related to DDAVP(R) (Desmopressin Acetate) ADHD(注意欠陥障害)治療薬 Shire Laboratories, Inc.'s Adderall XR(R) ナルコレプシー随伴の日中過眠治療薬 Cephalon, Inc.'s Provigil(R)(Modafinil) わが社製品の50%がFDAでpending、50%は開発中。 2003末、Bayer's $1 billion Cipro(R)のジェネリックを発売した。 そのCiprofloxacin製品は2003-Q4期売上$111 million達成。 Bayer社との1997年のCipro agreementにより、バイエル社特許切れ６カ月前に発売できた。 ※Additional Proprietary Activities In August 2002, we expanded our Cenestin line with the launch of the 0.3 mg strength. We also continue to work closely with FDA to provide additional data to support the approval of our 0.45 mg strength of Cenestin. In addition to the proprietary development activities related to SEASONALE and the expansion of Barr's Cenestin product line, we have five other projects in Phase III and Phase IV clinical development. These include the development of a low-dose version of SEASONALE, where a Phase IIIB clinical trial is underway and a NDA could be submitted during fiscal 2004; as well as the Company's DP3 extended cycle oral contraceptive. Trials for DP3 were initiated during the fourth quarter of fiscal 2002, and an application for the product could be filed with the FDA as early as fiscal 2005. Patent applications have been filed on this product. We are continuing the development of our vaginal ring technology, with the first product for urinary incontinence being developed for Schering AG. Other products are also under development using this novel drug delivery technology. ※Progress with Adenovirus Vaccine 以下略 - Annual Report 2003[pdf, 60p]
先発品 売上高*
($ Millions)薬効分野 Allegra(R) & Allegra(R) D
(Fexofenadine HCl and Fexofenadine HCl & Pseudoephedrine HCl)$ 1,874 Antihistamines Evista(R)
(Raloxifene HCl)$ 717 Female Healthcare Adderall XR(R)
(Amphetamine Salts Combination)$ 873 ADHD Provigil(R)
(Modafinil)$ 496 Narcolepsy Ortho Tri-Cyclen(R) Lo
(Norgestimate/Ethinyl Estradiol)$ 284 Oral Contraceptive ZYPREXA(R) Zydis(R)
(Olanzipine)$ 241 Psychotherapeutic ACTIQ(R)
(Fentanyl Citrate)$ 406 Oncology Yasmin(R)
(Drospirenone & Ethinyl Estradiol)$ 372 Oral Contraceptive Razadyne(R)
(Galantamine Hydrobromde)$ 245 Alzheimer's Total $ 5,508
●Barr Laboratories, Inc - http://www.barrlabs.com/home.html ●Product Guide - Barr扱いとDuramed扱いと二本立てになっていて Plan B ■Investor Relations ●Annual reports - Fiscal 2006 Annual Report[pdf,64p] - Annual Report 2005[pdf, 60p] - Annual Report 2004[pdf, 60p] - Annual Report 2003[pdf, 60p] ●[SEC]Company Search - >Barr Laboratories, Inc ●SEC Filings - 10-K[2008.2.29] - 10-KT[2007.3.1] - [pdf] - 今期から決算期変更 - 10-K[2006.8.30] - [pdf] - 10-K[2005.9.13] - [pdf] - 10-K[2004.8.24] - ★Press Releases ●News/ Press Releases 2005 | 2004 | 2003 | 2002 | 2001 | 2000 | 1999 | 1998 | 1997 | 1996 | 1995 Duramed Completes Acquisition of FEI Women's Health and ParaGard(R) IUD Product[2005.11.10] - FEI Women's Health, LLCの買収完了。同社は１０年間避妊防止のParaGard(R) T 380A (Intrauterine Copper Contraceptive) IUDを製造。 買収価格$281.5 million Barr Confirms FTC Lawsuit Related to Generic Ovcon-35(R) License[2005.11.7] - Duramed and Paladin Sign SEASONALE(R) Product Canadian License and Distribution Agreement[2005.10.26] - Duramed to Acquire FEI Women's Health and Its ParaGard(R) IUD Product[2005.10.18] - Barr's Duramed Acquires Exclusive Rights to Nordette(R)[2004.12.28] - Nordette(R) (levonorgestrel and ethinyl estradiol) Tabletsの米国独占権をKing Pharmaceuticals, Inc社から獲得。買収価格$12 million 適応症はfor the prevention of pregnancy in women who elect to use this product as a method of contraception Barr's Duramed to Acquire Exclusive Rights to Prefest(R)[2004.11.22] - Prefest(R) (estradiol/norgestimate) Tabletsの米国独占権をKing Pharmaceuticals , Inc社から獲得。買収価格$15 million 適応症はin women with an intact uterus for the treatment of moderate to severe vasomotor symptoms associated with the menopause, treatment of vulvar and vagin al atrophy and prevention of postmenopausal osteoporosis. Barr and Galen Announce Agreements for Duramed to Acquire Exclusive Rights to
Galen's Loestrin(R) Oral Contraceptive Products[2004.3.25] - Loestrin(R) and Loestrin(R) FE の米国・カナダの独占権をGalen Holdings PLC から獲得。買収価格$45 million Barr Completes Acquisition of Women's Capital Corporation and Plan B(R) Emergency Contraceptive[2004.2.26] - 私企業WCCを買収。買収価格$21 million 2003.12.16 FDA諮問委は緊急避妊薬Plan Bを処方箋薬からOTC Onlyへと移行することに 23対4 で承認勧告。 緊急避妊薬発売101カ国中、処方箋を要求しないのは３３カ国。
■Cephalon Inc
- http://www.cephalon.com/ バイオ企業、1987年設立；従業員数3,726人。 本社米国West Chester, Pennsylvania 米国で３新薬を含む世界で２０製品を販売 2000.10.10 Anesta Corp.[米]を買収、100%子会社とする。同社名のまま存続。 (ACTIQ(R) (oral transmucosal fentanyl citrate)を手に入れた ) 2001.12.28 Group Lafon(Laboratoire L Lafonが中核)[仏]の買収完了。 (Provigilの開発元)(買収額$454.2 million)。同社名のまま存続。 2004.08.12 CIMA LABS INCの全株を買収。 2005.7.18 CTI Technologies, Inc(CTIの完全子会社)を買収。 TRISENOX injection事業を継承。 2005.6.14 Salmedix, Inc.を買収。(現金$160m+$40m) その結果TREANDA(bendamustine HCl) CLL(慢性リンパ性白血病)の米国・カナダの開発・販売権も承継。 本剤はFDA申請2007.9(CLL;承認2008.3.20),2007.12(NHL)。 現在ドイツ・アステラス社がCephalon社にライセンス契約。独でRibomustin (Mundipharma)が販売、アジアはシンバイオ製薬㈱が独占権保持。 2005.12.22 Zeneus Holdings Limited の全株買収。 2007.8 AMRIX(筋弛緩剤)の北米独占権をE. Claiborne Robins Company, Inc.,および ECR Pharmaceuticalsから獲得。($100.1 million) 本剤は2007.2 FDA承認、当社は2007.10発売 2009.08.10 豪Arana Therapeutics Limitedを買収。ART621 2010.04.09 瑞Mepha AGを買収。 2010.2.01 2010.10.21 BioAssets Development Corporationを買収。TNF阻害薬CEP 37247 2011.2.9 Alba Therapeutics Corporationからセリアック病治療薬larazotide acetateの資産を買収 2011.03.21 Gemin X Pharmaceuticals, Incを買収～癌領域obatoclax (GX15-070), teglarinad (GMX1777), 2011.04.13 豪ChemGenex Pharmaceuticals Limited買収提案 2011.07.14 TevaがCephalonを買収。($6.8 billion) Teva to Acquire Cephalon in $6.8 Billion Transaction [2011.5.2] Cephalon Recommends Shareholders Reject Valeant Nominees[2011.4.7] Cephalon's Board of Directors Rejects Valeant Pharmaceuticals' Unsolicited Proposal[2011.4.5] Cephalon Confirms Receipt of Unsolicited Proposal from Valeant Pharmaceuticals[2011.3.28] ●決算＆売上■腫瘍領域 発売品は、TRISENOXの１製品を欧州同様に米国で販売。 欧州ではMYOCET (liposomal doxorubicin;乳癌)とTARGRETIN(bexarotene;皮膚T細胞性 リンパ腫)の２製品を販売。 パイプラインではTREANDA, a bi-functional hybrid cytotoxic;および CEP-701 (lestaurtinib), an oral small molecule tyrosine kinase inhibitor. ●CEP-701 (lestaurtinib) FLT-3-mutated AML適応でP3 , an oral small molecule tyrosine kinase inhibitor. CEP-701米国特許が2008迄だが延長申請。 [2007] AML患者のうちFLT-3遺伝子異常は25-30%。 Novartis and Millennium Pharmaceuticals が同様の作用機序の薬剤を開発中 ●TREANDA(bendamustine HCl) CLL(慢性リンパ性白血病)旧東ドイツ Jenapharm 社創薬 - 2005.6.14のSalmedix, Inc.を買収。(現金$160m+$40m)に伴うもので 本剤はFDA申請2007.9(CLL;承認2008.3.20),2007.12(NHL)。 現在ドイツ・アステラス社がCephalon社にライセンス契約。独でRibomustin (Mundipharma)が販売、アジアはシンバイオ製薬㈱が独占権保持。 【2010】 TREANDA is approved in the United States for the treatment of patients with chronic lymphocytic leukemia and patients with indolent B-cell non-Hodgkin's lymphoma ("NHL") whose disease has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. TREANDA comprised 14% and 10% of our total consolidated net sales for the years ended December 31, 2010 and 2009, respectively, all in the U.S. market.
($ milllion) 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 備考 総収入 2,811.057 2,192.308(+11) 1,974.554 1,772.638(-) 1,764.069(+46) 1,211.892(+19) 1,015.425(+42) 714.807 506.897 262.0 111.8 米国 1,808.229(+14) 1,580.336 1,433.670(-3) 1,472.674(+42) 1,034.032(+18) 872.678 欧州 384.079(-3) 394.218 338.968(+16) 291.395(+64) 177.860(+25) 142.747 製品売上 2,760.952(+28) 2,151.548(+11) 1,943.464 1,727.299(-) 1,720.172(+49) 1,156.518 980.375(+43) 685.250 465.943 226.1 91.6 米国 2,102.175(+19) 1,768.383(+14) 1,550.790 1,393.521(-3) 1,437.275(+46) 986.4(+17) 843.9 欧州 658.777(+72) 383.165(-2) 392.674 333.778(+18) 282.897(+66) 170.1(+25) 136.4 他の収入 50.105 40.760(+31) 31.090 45.339(+3) 43,897(-21) 55.374(+58) 35.050 29.557 40.954 35.9 20.2 米国 39.846(+35) 29.546 40.149(+13) 35.399(-26) 47.587(+66) 28.749 欧州 0.914(-41) 1.544 5.190(-39) 8.498(+9) 7.787(+24) 6.301 ●神経系 計 1,394.365(+18) 1,178.642
旧1,154.565(+10)1,049.115 909.357(+15) 794.118 米国 1,285.616(+18) 1,085.561(+11) 977.427 852.281(+14) 746.750 欧州 108.749(+17) 93.081
旧69.004(-4)71.688 57.076(+20) 47.368 PROVIGIL Tabs 1,124.494(+10) 1,024.688(+4) 988.418 852.047(+16) 734.831(+43) 512.805(+17) 439.667(+51) 290.5(+40) 207.2(+31) 150.3(+108.5) 72.1(+184) (modafinil)[C-IV] 米国 1,059.698(+10) 961.070(+4) 924.986 801.639(+16) 691.779(+45) 475.557(+17) 406.238 欧州 64.796(+2) 63.618(-) 63.432 50.408(+17) 43.052(+16) 37.248(+11) 33.429 GABITRIL 44.488(-21) 56.486(-7) 60.697 57.310(-3) 59.287(-18) 72.258(-23) 94.164(+48) 63.7(+31) 48.8(+) 24.6 - (tiagabine HCl)抗てんかん剤from Abbott 米国 39.728(-22) 51.100(-3) 52.441 50.642(-8) 54.971(-17) 66.517(-24) 87.349 欧州 4.760(-12) 5.386(-35) 8.256 6.668(+54) 4.316(-25) 5.741(-16) 6.815 NUVIGIL 186.190(+154) 73.391(-) - [armodafini]目覚め改善 米国 186.190(+154) 73.391(-) - 欧州 - - - - ●疼痛 計 526.291(+6) 494.310
旧485.089(-3)501.168 512.642(-23) 661.693 米国 373.888(-9) 409.448(-5) 429.998 471.977(-26) 634.441 欧州 152.403(+80) 84.862
旧75.641(+6)71.170 40.665(+49) 27.252 ACTIQ 130.881(-11) 146.945(-17) 176.521 240.072(-58) 577.642(+40) 411.778(+19) 344.997(+45) 237.5(+87) 126.7(+146) 51.2(+734) 15.2 (oral transmucosal fentanyl citrate)[C-II]発売2000.10 Anesta Corp 米国 63.930(-15) 75.418(-28) 105.351 199.407(-64) 550.390(+39) 394.676(+17) 337.072 欧州 66.951(-6) 71.527(+1) 71.170 40.665(+49) 27.252(+59) 17.102(+116) 7.925 Generic OTFC 米国 41.138(-50) 83.032(-13) - 129.033(+135) 54.801(-) - - - - - - [oral transmucosal fentanyl citrate] FENTORA 181.622(+29) 140.677(-9) 155.246 135.136(+362) 29.250(-) - - - - - - [fentanyl buccal tablet][C-II]次世代鎮痛剤;発売2006.10 米国 159.585(+17) 136.563(-12) 155.246 135.136(+362) 29.250(-) - - - - - - 欧州 22.037(436) 4.114(-) - Amrix 米国 109.235(-5) 114.435(+55) 73.641 8.401 - - [持続性Cyclobenzaprine HCl]骨格筋弛緩剤 ●腫瘍用薬 513.593(+53) 335.863(+81) 185.617(+100) 92.877 米国 414.339(+72) 240.393(+157) 93.698(+466) 16.561 欧州 99.254(+3) 95.470(+4) 91.919(+20) 76.316 TREANDA 米国 393.473(+77) 222.122(+196) 75.132 - - - - - [bendamustine HCl]非ホジキンリンパ腫・慢性リンパ球白血病[CLL] 他の腫瘍用薬 97.122(4) 93.641
旧113.751(+3)110.485(+19) 92.877 米国 20.866(+14) 18.281(-2) 18.566(+12) 16.561 欧州 76.256(+1) 75.360
旧95.470(+4)91.919(+20) 76.316 ●その他製品 326.703(+130) 141.903
旧176.031(-15)207.564 305.300(+15) 264.361(+66) 159.677 101.547(+8) 93.6(+12) 83.3 米国 28.232(-14) 32,981
旧32.581(-34)49.667 69.263(+23) 56.084(+13) 49.695(+274) 13.270 欧州 298.371(+174) 108.922
旧143.050(-9)157.897 236.037(+13) 208.277(+89) 109.982(+25) 88.277 営業利益 717.557 333.965 (99.143) 294.137 -222.958 13.434 156.0 経常利益 618.799 289.407 (68.419) 238.254 -245.118 -28.184 130.3 純利益 417.683 210.727 171.889 (191.704) 144.816 -174.954 -73.813 83.858 171.528 -55.5 -60.2 研究開発費 439..995 395.431(+9) 362.208 369.115(-13) 403.367 354.826 274.0 168.2 買収研究開発 100.000 46.118 41.955 - 5.000 366.815 185.700 - - 20.0 - 従業員数 3,726 2,796 2,895 We are currently conducting a Phase III clinical trial of TREANDA in combination with RITUXAN as a front-line treatment for NHL. While not a currently approved indication by the FDA, TREANDA was recently listed in the 2010 NCCN clinical practice guidelines and the Clinical Pharmacology compendia as a front-line treatment for NHL. Separately, the results of an independent Phase III clinical study conducted by the German Study for Indolent Lymphomas Group ("StiL Group") in Giessen, Germany were announced in December 2009. The study for the first-line treatment of patients with advanced follicular, indolent, and mantle cell lymphomas, indicated better tolerability and more than a 20-month improvement in median progression free survival when treated with TREANDA in combination with rituximab compared to cyclophosphamide, doxorubicin, vincristine, and prednisone ("CHOP") in combination with rituximab. The indications covered by the study are not currently FDA-approved indications for TREANDA. We plan to submit the StiL Group's study results to support an sNDA for TREANDA for the treatment of front-line NHL in 2011.
[2007] CLLの年間新患は米国で15,000人。 CLLの第一選択剤はLeukeran(Chlorambucil;GSK)。 Campath(R)(alemtuzumab) by Bayer ;との競合となる。 NHLでは、cyclophosphamide, vincristine and prednisolone併用、 BEXXAR(R) (131-I tositumomab) by GlaxoSmithKline との競合となろう。 ●TRISENOX(砒素三酸化物Arsenic Trioxide) ★CTIはTrisenoxをCephalonに譲渡。代価は$68million。2005.7 米国承認2000、欧州承認2002。適応症は再発または前治療無効の急性前骨髄球性白血病 (relapsed or refractory acute promyelocytic leukemia ("APL")) 日本では、トリセノックス[日本新薬] [2007] APLはacute myeloid or myelogenous leukemia ("AML")の８種の亜系の一つ。 米国ではAML患者数が毎年13,000人(American Cancer Society)発症し(9000人が死亡)、 うちAPLは10-15%、APLで治療抵抗性または再発するのは10-30%。 市場競合する薬剤は多い。VESANOID(R)[Roche]等。 [2006]In July 2005, we acquired substantially all of the assets related to the TRISENOX injection business from Cell Therapeutics, Inc. TRISENOX was approved for marketing in the United States and Europe in 2000 and 2002, respectively, for the treatment of patients with relapsed or refractory acute promyelocytic leukemia (“APL”), a life threatening hematologic cancer. APL is one of eight subtypes of acute myeloid or myelogenous leukemia (“AML”). According to the American Cancer Society, approximately 12,000 patients are diagnosed with AML in the United States every year, 10 to 15 percent of whom will have the APL subtype. Research indicates that approximately 10 to 30 percent of patients with APL will not respond to, or will relapse from, first-line therapy.TRISENOX is a highly purified salt of arsenic, a natural element. TRISENOX appears to have multiple targets and mechanisms of antileukemic activity; it degrades a protein that causes abnormal levels of immature white blood cells while simultaneously forcing immature cancer cells to self-destruct through a process called programmed cell death or apoptosis. Apoptosis is a normal part of a cell’s life cycle. Because cancer is often associated with a malfunction of the normal process of apoptosis, drugs that can induce apoptosis offer the hope of affecting cancer cells more selectively without the typical toxic side effects of conventional treatments. Direct induction of apoptosis represents a relatively new method of killing tumor cells that is different than the majority of conventional cancer drugs. As a result, in addition to its use as a single-agent therapy, TRISENOX may work well when administered in combination with other cancer therapies to produce more durable response rates.
In January 2007, the National Cancer Institute and one of its Cooperative Clinical Trial Groups announced positive results from a clinical trial using TRISENOX in newly diagnosed patients with APL. According to the NCI, the results of the trial showed that adult patients with previously untreated APL who had standard chemotherapy to induce remission of their disease, and who then received TRISENOX to maintain remission, had significantly better event-free survival and better overall survival than those who received only standard chemotherapy. We are continuing to investigate uses of TRISENOX, as a single agent or in combination with other treatments, to treat APL and other forms of hematologic cancers.
Intellectual Property Position
We have a license to patents and patent applications covering methods of treating APL with the active ingredient arsenic trioxide that protect this product until 2018. TRISENOX is also protected by orphan drug exclusivity until 2007. We also hold rights to the TRISENOX trademark.
Manufacturing and Product Supply
We have one third-party manufacturer that produces the active drug substance arsenic trioxide for us and two third-party manufacturers that provide finished commercial supplies of TRISENOX to us in the United States and Europe. We seek to maintain inventories of active drug substance and finished commercial supplies to protect against supply disruptions.
Competition
The pharmaceutical market for the treatment of patients with relapsed or refractory APL is served by a number of available therapeutics, such as VESANOIDR by Roche in combination with chemotherapy.
★PROVIGIL(R) (modafinil) Tablets [C-IV] 2001.12.28 Group Lafon(Laboratoire L Lafonが中核)[仏]の買収完了。 (Provigilの開発元)(買収額$454.2 million)。同社名のまま存続。【2010】
PROVIGIL is indicated for the treatment of excessive sleepiness associated with narcolepsy, OSA/HS and SWSD and was launched in 1999. PROVIGIL comprised 41% and 48% of our total consolidated net sales for the years ended December 31, 2010 and 2009, respectively, of which 94% was in the U.S. market for each year. We expect that PROVIGIL will face generic competition in the United States beginning in April 2012 and, as a result, PROVIGIL sales will materially decline. In clinical studies, PROVIGIL was generally well-tolerated, with a low incidence of adverse events relative to placebo. The most commonly observed adverse events were headache, infection, nausea, nervousness, anxiety and insomnia.Outside of the U.S., modafinil currently is approved in more than 30 countries, including France, the United Kingdom, Ireland, Italy and Germany, for the treatment of excessive daytime sleepiness associated with narcolepsy. In certain of these countries, we also have approval to market modafinil to treat excessive daytime sleepiness in patients with OSA/HS and/or SWSD.
【2009】
Modafinil, the active ingredient in PROVIGIL, is the first in a new class of wake-promoting agents. While its exact mechanism of action remains to be fully elucidated, modafinil appears to act selectively in regions of the brain believed to regulate normal sleep and wakefulness. The FDA approved PROVIGIL to improve wakefulness in patients with excessive daytime sleepiness associated with narcolepsy, and we launched the product in the United States in February 1999. In January 2004, we received FDA approval to expand the label for PROVIGIL to include improving wakefulness in patients with excessive sleepiness associated with OSA/HS and SWSD. In clinical studies, PROVIGIL was generally well-tolerated, with a low incidence of adverse events relative to placebo. The most commonly observed adverse events were headache, infection, nausea, nervousness, anxiety and insomnia.Outside of the U.S., modafinil currently is approved in more than 30 countries, including France, the United Kingdom, Ireland, Italy and Germany, for the treatment of excessive daytime sleepiness associated with narcolepsy. In certain of these countries, we also have approval to market modafinil to treat excessive daytime sleepiness in patients with OSA/HS and/or SWSD.
Indicated Diseases/Disorders
Narcolepsy: Narcolepsy is a debilitating, lifelong sleep disorder whose symptoms often first arise in late childhood. Its most common symptom is an uncontrollable propensity to fall asleep during the day. PROVIGIL has been recognized by the American Academy of Sleep Medicine as a standard of therapy for the treatment of excessive daytime sleepiness associated with narcolepsy.
Obstructive Sleep Apnea/Hypopnea Syndrome (OSA/HS): Individuals with OSA/HS experience frequent awakenings, sometimes occurring hundreds of times during the night as a result of blockage of the airway passage, usually caused by the relaxation and collapse of the soft tissue in the back of the throat during sleep. Continuous positive airway pressure ("CPAP"), a medical device that blows air through the nasal passage, is the primary treatment for OSA/HS. However, approximately 30 percent of patients that use CPAP continue to experience excessive sleepiness, for which PROVIGIL and NUVIGIL may be an appropriate adjunctive treatment.
Shift Work Sleep Disorder (SWSD): SWSD is defined as a persistent or recurrent pattern of sleep disruption that leads to excessive sleepiness or insomnia due to a mismatch between the natural circadian sleep-wake pattern and the sleep-wake schedule required by a person's environment. SWSD particularly affects those who frequently rotate shifts or work at night, which is contrary to the body's natural circadian rhythms.
Intellectual Property Position
We own various U.S. and foreign patent rights that expire between 2014 and 2015 and cover pharmaceutical compositions and uses of modafinil, including the commercial formulation of PROVIGIL. We also hold rights to other patents and patent applications directed to polymorphs, manufacturing processes, formulations, and uses of modafinil and to next-generation modafinil products. We also own rights to PROVIGIL and other various trademarks for our pharmaceutical products containing the active drug substance modafinil. Ultimately, these patents and patents related to our other products and product candidates might be found invalid if challenged by a third party, or a potential competitor could develop a competing product that avoids infringement of these patents.
With respect to NUVIGIL, we successfully obtained issuance of a U.S. patent in November 2006 claiming the Form I polymorph of armodafinil, the active drug substance in NUVIGIL. This patent is currently set to expire in 2023. Foreign patent applications directed to the Form I polymorph of armodafinil and its use in treating sleep disorders are pending in Europe and elsewhere. In addition, the particle size patent described above for PROVIGIL also covers NUVIGIL. We also received a three year period of marketing exclusivity (until early 2010). We also hold rights to other patent applications directed to other polymorphic forms of armodafinil and to the manufacturing process related to armodafinil. We hold rights to the NUVIGIL trademark.
Regarding our ongoing NUVIGIL patent lawsuits and PROVIGIL settlements and related lawsuits, please see Note 16 to our Consolidated Financial Statements included in Part II, Item 8 of this Annual Report on Form 10-K, which is incorporated herein by reference. While we intend to vigorously defend the NUVIGIL intellectual property rights and the propriety of the PROVIGIL settlements, these efforts will be both expensive and time consuming and, ultimately, due to the nature of litigation, there can be no assurance that these efforts will be successful.
Manufacturing and Product Supply
We have third party agreements with four companies to supply us with modafinil (which requirements include certain minimum purchase requirements) and two companies to supply us with finished commercial supplies of PROVIGIL. With respect to NUVIGIL, we have three third parties who manufacture the active drug substance armodafinil and one qualified manufacturer of finished supplies of NUVIGIL tablets. At our manufacturing facility in Mitry-Mory, France, we produce modafinil for use in the production of PROVIGIL. We seek to maintain inventories of active drug substance and finished products to protect against supply disruptions. Any future change in manufacturers or manufacturing processes requires regulatory approval.
Competition
With respect to PROVIGIL and NUVIGIL, there are several other products used for the treatment of excessive sleepiness or narcolepsy in the United States. Many of these products, including methylphenidate products, have been available for a number of years and are available in inexpensive generic forms. We also are aware of numerous companies seeking to develop products to treat excessive sleepiness.
We have filed against Actavis Pharma Manufacturing Pvt Ltd. ("Actavis"), Mylan, Sandoz, Inc. ("Sandoz"), Teva Pharmaceuticals USA, Inc. ("Teva") and Watson :the NUVIGIL patent infringement lawsuits
【2006】
Our most significant product is PROVIGIL(R) (modafinil) Tablets [C-IV], which comprised approximately 43% of our total consolidated net sales for the year ended December 31, 2006, of which approximately 94% was in the U.S. market. For the year ended December 31, 2006, consolidated net sales of PROVIGIL increased 43% over the year ended December 31, 2005. Under our co-promotion agreement with Takeda Pharmaceuticals North America, Inc., 500 Takeda sales representatives began promoting PROVIGIL in the second position to primary care physicians and other appropriate health care professionals in the United States beginning July 1, 2006. Effective January 1, 2007, an additional 250 Takeda sales representatives were added, all of whom are detailing PROVIGIL in the first position. Together with our CNS field sales and sales management teams, we now have nearly 1,200 persons focused on detailing PROVIGIL in the United States.The U.S. composition of matter patent for modafinil expired in 2001. We own U.S. and foreign patent rights that expire between 2014 and 2015 and cover pharmaceutical compositions and uses of modafinil, specifically, certain particle sizes of modafinil contained in the pharmaceutical composition of PROVIGIL. With respect to NUVIGIL, we successfully obtained issuance of a U.S. patent in November 2006 claiming the Form I polymorph of armodafinil, the active drug substance in NUVIGIL. This patent is currently set to expire in 2023. Foreign patent applications directed to the use of the Form I polymorph of armodafinil in treating sleep disorders are pending in Europe and elsewhere. Ultimately, these patents might be found invalid as the result of a challenge by a third party, or a potential competitor could develop a competing product or product formulation that avoids infringement of these patents. While we intend to vigorously defend the validity of these patents and prevent infringement, these efforts will be both expensive and time consuming and, ultimately, may not be successful. The loss of patent protection for PROVIGIL would significantly and negatively impact future PROVIGIL sales.
As of the filing date of this Annual Report on Form 10-K, we are aware of seven ANDAs on file with the FDA for pharmaceutical products containing modafinil. Each of these ANDAs contains a Paragraph IV certification in which the ANDA applicant certified that the U.S. particle-size modafinil patent covering PROVIGIL either is invalid or will not be infringed by the ANDA product. In March 2003, we filed a patent infringement lawsuit against four companies?Teva Pharmaceuticals USA, Inc., Mylan Pharmaceuticals, Inc., Ranbaxy Laboratories Limited and Barr Laboratories, Inc.?based upon the ANDAs filed by each of these companies with the FDA seeking approval to market a generic form of modafinil. We believe that these four companies were the first to file ANDAs with Paragraph IV certifications and thus are eligible for the 180-day exclusivity provided by the provisions of the Federal Food, Drug and Cosmetic Act.
In late 2005 and early 2006, we entered into settlement agreements with each of these four defendants. As part of these separate settlements, we agreed to grant to each of Teva, Mylan, Ranbaxy and Barr a non-exclusive royalty-bearing right to market and sell a generic version of PROVIGIL in the United States. These licenses will become effective in April 2012. An earlier entry may occur based upon the entry of another generic version of PROVIGIL. Each of these settlements, as well as the ACTIQ settlement agreement described below, has been filed with both the FTC and the Antitrust Division of the DOJ as required by the Medicare Modernization Act. The FTC has requested from us, and we have provided, certain information in connection with its review of the settlements. In July 2006, the FTC requested that we voluntarily submit additional information and documents in connection with its investigation of the PROVIGIL settlements. We are cooperating fully with this request. The FTC could challenge in an administrative or judicial proceeding any or all of the settlements if they believe that the agreements violate the antitrust laws, although we believe that such a challenge would take years to resolve.
We also are aware of a number of civil antitrust complaints, purportedly filed as class actions, filed by private parties in U.S. District Court for the Eastern District of Pennsylvania, each naming Cephalon, Barr, Mylan, Teva and Ranbaxy as co-defendants and claiming, among other things, that the patent litigation settlements concerning PROVIGIL violate the antitrust laws of the United States and certain state laws. The proposed consolidated class action complaints have been designated by plaintiffs, each of which seeks to certify separate, purported classes of plaintiffs: direct purchasers of PROVIGIL, and consumers and other indirect purchasers of PROVIGIL. The plaintiffs in both cases are seeking monetary damages and/or equitable relief. Separately, in June 2006, Apotex, Inc., a subsequent ANDA filer seeking FDA approval of a generic form of modafinil, filed suit against us also in the U.S. District Court for the Eastern District of Pennsylvania alleging similar violations of antitrust laws and state law. Apotex asserts that the PROVIGIL settlement agreements improperly prevent it from obtaining FDA approval of its ANDA, and seeks monetary and equitable remedies, including a declaratory judgment that our U.S. Patent No. RE37,516 (the “‘516 Patent”) is invalid and unenforceable. We filed a motion to dismiss the Apotex case in late September 2006. We believe that both the purported class action cases and the Apotex case are without merit. While we intend to vigorously defend ourselves and the propriety of the settlement agreements, these efforts will be both expensive and time consuming and, ultimately, due to the nature of litigation, there can be no assurance that these efforts will be successful.
In early 2005, we also filed a patent infringement lawsuit against Carlsbad Technology, Inc. based upon the Paragraph IV ANDA filed related to modafinil that Carlsbad filed with the FDA. In August 2006, we entered into a settlement agreement with Carlsbad and its development partner, Watson Pharmaceuticals, Inc., which we understand has the right to commercialize the Carlsbad modafinil product if approved by FDA. As part of this settlement, we agreed to grant to Watson a non-exclusive royalty-bearing right to market and sell a generic version of PROVIGIL in the United States. This license will become effective on or after April 6, 2012, subject to applicable regulatory considerations. An earlier entry may occur based upon the entry of another generic version of PROVIGIL. This agreement has been filed with both the FTC and DOJ, as required by the Medicare Modernization Act.
In November 2005 and March 2006, we received notice that Caraco Pharmaceutical Laboratories, Ltd. and Apotex, Inc., respectively, also filed Paragraph IV ANDAs with the FDA in which each firm is seeking to market a generic form of PROVIGIL. We have not filed patent infringement lawsuits against either Caraco or Apotex as of the filing date of this report, although Apotex has filed suit against us, as described above.
Co-Promotion Agreement with Takeda
On June 12, 2006, we entered into a co-promotion agreement with Takeda with respect to PROVIGIL in the United States. Under the co-promotion agreement, 500 Takeda sales representatives began promoting PROVIGIL in the second position to primary care physicians and other appropriate health care professionals in the United States beginning July 1, 2006. Effective January 1, 2007, an additional 250 Takeda sales representatives were added, all of whom are detailing PROVIGIL in the first position. Together with our CNS field sales and sales management teams, we now have nearly 1,200 persons focused on detailing PROVIGIL in the United States. We also have an option to utilize the Takeda sales force for the promotion of NUVIGIL, assuming FDA approval of this product candidate. The parties have formed a joint commercialization committee to manage the promotion of PROVIGIL. We have retained all responsibility for the development, manufacture, distribution and sale of the product.
The co-promotion agreement has a three-year term. If we undergo a change of control during the three-year term, we have the option to terminate the co-promotion agreement, subject to our obligation to make certain specified payments to Takeda. We pay Takeda a royalty based on certain sales criteria for PROVIGIL and NUVIGIL during the three-year term and, if specified sales levels are reached, during the three calendar years following the expiration of the co-promotion agreement.
Targeted Diseases/Disorders
Narcolepsy: Narcolepsy is a debilitating, lifelong sleep disorder whose symptoms often first arise in late childhood. Its most common symptom is an uncontrollable propensity to fall asleep during the day. PROVIGIL has been recognized by the American Academy of Sleep Medicine as a standard of therapy for the treatment of excessive daytime sleepiness associated with narcolepsy.
OSA/HS: Individuals with OSA/HS experience frequent awakenings, sometimes occurring hundreds of times during the night as a result of blockage of the airway passage, usually caused by the relaxation and collapse of the soft tissue in the back of the throat during sleep. Continuous positive airway pressure (“CPAP”), a medical device that blows air through the nasal passage, is the primary treatment for OSA/HS. However, approximately 30 percent of patients that use CPAP continue to experience excessive sleepiness, for which PROVIGIL may be an appropriate adjunctive treatment.
SWSD: SWSD is defined as a persistent or recurrent pattern of sleep disruption that leads to excessive sleepiness or insomnia due to a mismatch between the natural circadian sleep-wake pattern and the sleep-wake schedule required by a person’s environment. SWSD particularly affects those who frequently rotate shifts or work at night, which is contrary to the body’s natural circadian rhythms.
Intellectual Property Position
We own various U.S. and foreign patent rights that expire between 2014 and 2015 and cover pharmaceutical compositions and uses of modafinil, specifically, certain particle sizes of modafinil contained in the pharmaceutical composition of PROVIGIL. We also hold rights to other patents and patent applications directed to polymorphs, manufacturing processes, formulations, and uses of modafinil and to next-generation modafinil products. We also own rights to PROVIGIL and other various trademarks for our pharmaceutical products containing the active drug substance modafinil. Ultimately, these patents and patents related to our other products and products candidates might be found invalid if challenged by a third party, or a potential competitor could develop a competing product or product formulation that avoids infringement of these patents.
In late 2005 and early 2006, we entered into settlement agreements with each of Teva, Mylan, Ranbaxy and Barr. As part of these separate settlements, we agreed to grant to each of these parties a non-exclusive royalty-bearing right to market and sell a generic version of PROVIGIL in the United States. These licenses will become effective in April 2012. An earlier entry may occur based upon the entry of another generic version of PROVIGIL. Each of these settlements has been filed with both the United States Federal Trade Commission (the “FTC”) and the Antitrust Division of the Department of Justice (the “DOJ”) as required by the Medicare Prescription Drug, Improvement and Modernization Act of 2003 (the “Medicare Modernization Act”). The FTC has requested from us, and we have provided, certain information in connection with its review of the PROVIGIL settlements. In July 2006, the FTC requested that we voluntarily submit additional information and documents in connection with its investigation of this matter. We are cooperating fully with this request. The FTC could challenge in an administrative or judicial proceeding any or all of the settlements if they believe that the agreements violate the antitrust laws, although we believe that such a challenge would take years to resolve.
★NUVIGIL(TM) (armodafinil)【2010】
NUVIGIL, a single-isomer formulation of modafinil, is indicated for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome ("OSA/HS") and shift work sleep disorder ("SWSD") and was launched in June 2009. NUVIGIL comprised 7% and 3% of our consolidated net sales for the years ended December 31, 2010 and 2009, respectively, all in the U.S. market.In March 2009, we announced positive results from a Phase II clinical trial of NUVIGIL as adjunctive therapy for treating major depressive disorder in adults with bipolar I disorder. We have initiated two Phase III clinical trials, which we expect to complete in late 2011 or early 2012 and will initate a third in 2011, which we expect to complete in late 2012 or early 2013. In June 2010, we announced that the primary endpoint was not met for a Phase II study of NUVIGIL as an adjunctive therapy for the treatment of the negative symptoms of schizophrenia. In 2010, we also decided to discontinue our clinical studies regarding NUVIGIL as a treatment of traumatic brain injury due to slow patient enrollment. In December 2010, we announced that we will not pursue further lag indication for NUVIGIL. In January 2011, we announced positive results from a phase IV clinical trial of NUVIGIL in patients experiencing excessive sleepiness associated with shift work disorder, specifically during the end of their night shifts (i.e., 4:00 a.m. to 8:00 a.m.), including the commute home. The study data showed statistically significant improvement in overall clinical condition related to late-shift sleepiness in patients receiving NUVIGIL compared to the placebo group. This was the largest trial ever conducted in this patient population, with more than 380 patients randomized to treatment with NUVIGIL or placebo.
In clinical studies, NUVIGIL was generally well-tolerated. The most common side effects were mainly mild to moderate in severity and included nausea, headaches, dizziness, diarrhea, decreased appetite and upset stomach.
【2009】
An important focus of our modafinil strategy has been the development of our next-generation compound, NUVIGIL, a single-isomer formulation of modafinil. In June 2007, we received final FDA approval to market NUVIGIL for the treatment of excessive sleepiness associated with narcolepsy, OSA/HS and SWSD. The product is protected by a composition of matter patent that will expire on December 18, 2023 and covers a novel polymorphic form of armodafinil, the active pharmaceutical ingredient in NUVIGIL. We launched NUVIGIL on June 1, 2009. In March 2009, we announced positive results from a Phase II clinical trial of NUVIGIL as adjunctive therapy for treating major depressive disorder in adults with bipolar I disorder and our plan to advance to Phase III trials for this indication. In April 2009, we announced positive results from a Phase III clinical trial of NUVIGIL as a treatment for excessive sleepiness associated with jet lag disorder and filed a supplemental new drug application (an "sNDA") for this indication with the FDA in June 2009. We expect a response from the FDA by March 29, 2010. In May 2009, we announced positive results from a Phase IV study of NUVIGIL in obstructive sleep apnea and comorbid major depressive disorder requiring ongoing antidepressant therapy. We also have ongoing clinical studies for NUVIGIL focused on adjunctive treatment to atypical anti-psychotics in schizophrenia patients, adjunctive treatment for bi-polar depression and excessive sleepiness associated with traumatic brain injury. In clinical studies, NUVIGIL was generally well-tolerated. The most common side effects were mainly mild to moderate in severity and included nausea, headaches, dizziness, diarrhea, decreased appetite and upset stomach. Our most significant products are our wakefulness products, PROVIGIL®(modafinil) Tablets [C-IV] and NUVIGIL®(armodafinil) Tablets [C-IV], which comprised 51% of our total consolidated net sales for the year ended December 31, 2009, of which 94% was in the U.S. market. For the year ended December 31, 2009, combined consolidated net sales of PROVIGIL and NUVIGIL increased 11% over the year ended December 31, 2008. In June 2007, we secured final U.S. Food and Drug Administration (the "FDA") approval of the NUVIGIL indication for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome ("OSA/HS") and shift work sleep disorder ("SWSD"). We launched NUVIGIL on June 1, 2009. In March 2009, we announced positive results from a Phase II clinical trial of NUVIGIL as adjunctive therapy for treating major depressive disorder in adults with bipolar I disorder and our plan to advance to Phase III trials for this indication. In April 2009, we announced positive results from a Phase III clinical trial of NUVIGIL as a treatment for excessive sleepiness associated with jet lag disorder and filed a supplemental new drug application (an "sNDA") for this indication with the FDA in June 2009. We expect a response from the FDA by March 29, 2010. In May 2009, we announced positive results from a Phase IV study of NUVIGIL in obstructive sleep apnea and co-morbid major depressive disorder requiring ongoing antidepressant therapy. 【2006】
We also made progress in 2006 toward the approval of NUVIGIL? (armodafinil) with an anticipated indication for excessive sleepiness. NUVIGIL is a single-isomer version of modafinil, the active ingredient in PROVIGIL. In May 2006, we received an approvable letter from the FDA; we currently expect a final approval decision from the FDA on or before March 31, 2007. The FDA is continuing to evaluate the single case of serious rash reported in a SPARLON(TM) (modafinil) Tablets [C-IV] clinical study discussed below. We have provided additional information to the FDA to help the agency place this isolated case in the context of the safety profile for modafinil that has been established over more than a decade of commercial use. The reviewing division has not requested any additional information related to NUVIGIL and is working with us to finalize the product’s label. Since NUVIGIL is derived from the active ingredient in PROVIGIL, we expect that the safety information in the PROVIGIL label will be appropriately modified to reflect the safety information in the final NUVIGIL label. NUVIGIL is protected by a composition of matter patent that will expire on December 18, 2023 and covers a novel polymorphic form of armodafinil, the active pharmaceutical ingredient in NUVIGIL.An important focus of our modafinil strategy has been the development of next-generation compounds, including NUVIGIL, a single-isomer formulation of modafinil. In March 2005, we filed a new drug application (“NDA”) with the FDA seeking approval to market NUVIGIL with the same labeled indications as PROVIGIL. In May 2006, we received an approvable letter from the FDA; we currently expect a final approval decision from the FDA on or before March 31, 2007. We are planning to transition our wakefulness franchise to NUVIGIL around 2010, prior to the April 2012 license effectiveness dates under the generic settlement agreements related to PROVIGIL. The FDA is continuing to evaluate the single case of serious rash reported in a SPARLON (modafinil) clinical study. We have provided additional information to the FDA to help the agency place this isolated case in the context of the safety profile for modafinil that has been established over more than a decade of commercial use. The reviewing division has not requested any additional information related to NUVIGIL and is working with us to finalize the product’s label. Since NUVIGIL is derived from the active ingredient in PROVIGIL, we expect that the safety information in the PROVIGIL label will be appropriately modified to reflect the safety information in the final NUVIGIL label.
In Phase 3 clinical trials of 150- and 250-milligram daily doses of NUVIGIL in patients suffering from excessive sleepiness associated with narcolepsy, SWSD or OSA/HS, results indicate that NUVIGIL significantly improves wakefulness and the overall clinical condition of patients as compared to placebo. The 12-week, double-blind, randomized, placebo-controlled Phase 3 studies of approximately 1,000 patients included one study of excessive sleepiness in narcolepsy, one study in SWSD and two studies in OSA/HS. The primary endpoints in each Phase 3 study were measures of objective sleep latency (Maintenance of Wakefulness Test or Multiple Sleep Latency Test) and the physician rating of Clinical Global Impression-Change. These primary endpoints are identical to those studied for the currently approved indications for PROVIGIL. In each Phase 3 study, patients treated with NUVIGIL showed a highly statistically significant improvement on both primary endpoints compared to placebo. In these studies, NUVIGIL was generally well-tolerated. The most commonly observed adverse effects included headache, nausea, dizziness, insomnia and anxiety.
In 2007, we expect to initiate clinical studies of NUVIGIL in bi-polar depression, cognition in schizophrenia and excessive sleepiness and fatigue in conditions such as Parkinson’s Disease and cancer. If the results of any of these studies are positive, we plan to seek an expansion of the labeled indications for NUVIGIL.
★ACTIQ(R) (oral transmucosal fentanyl citrate) 2000.10.10 Anesta Corp.[米]を買収、100%子会社とする。同社名のまま存続。 (ACTIQ(R) (oral transmucosal fentanyl citrate)を手に入れた ) Cephalon and Anesta Announce Merger to Create Stronger, More Profitable Pharmaceutical Business[2000.7.17] - Cephalon, Inc. (Nasdaq: CEPH)はAnesta Corpを買収することに両社が合意。 【2009】On a combined basis, our two next most significant products are FENTORA® (fentanyl buccal tablet) [C II] and ACTIQ® (oral transmucosal fentanylcitrate) [C II] (including our generic version of ACTIQ ("generic OTFC")). Together, these products comprise 17% of our total consolidated net sales forthe year ended December 31, 2009, of which 80% was in the U.S. market. In October 2006, we launched FENTORA in the United States. FENTORA isindicated for the management of breakthrough pain in patients with cancer who are already receiving and are tolerant to opioid therapy for their underlyingpersistent cancer pain. In April 2008, we received marketing authorization from the European Commission for EFFENTORA™ for the same indication asFENTORA and launched the product in certain European countries in January 2009. We have focused our clinical strategy for FENTORA on studying theproduct in opioid tolerant patients with breakthrough pain associated with chronic pain conditions, such as neuropathic pain and back pain. In November2007, we submitted an sNDA to the FDA seeking approval to market FENTORA for the management of breakthrough pain in opioid tolerant patients withchronic pain conditions. In early April 2009, we submitted a Risk Evaluation and Mitigation Strategy (the "REMS Program") with respect to FENTORA.Subject to the timing and nature of further discussions with the FDA, we expect to receive a response from the FDA regarding the FENTORA REMSProgram by the middle of 2010. For more information regarding our FENTORA REMS Program, please see "PainkﾀFENTORA" below. With respect toACTIQ, its sales have been meaningfully eroded by the launch of FENTORA and by generic OTFC products sold since June 2006 by BarrLaboratories, Inc. and by us through our sales agent, Watson Pharmaceuticals, Inc. We expect this erosion will continue. In September 2009, our obligationto supply Barr with generic OTFC ended pursuant to the terms of a license and supply agreement we entered into with Barr in July 2004. In October 2009,we understand that the FDA approved ANDAs by Barr and by Covidien to market and sell generic OTFC. We submitted our REMS Program for ACTIQand generic OTFC in early April 2009. We expect to receive a response from the FDA by the middle of 2010.ACTIQ uses an oral transmucosal delivery system ("OTS®") to deliver fentanyl citrate, a powerful, Schedule II opioid analgesic. The OTS deliverysystem consists of a drug matrix that is mounted on a handle. It is designed to achieve rapid absorption of fentanyl through the oral mucosa and into thebloodstream, with pain relief that may begin within 15 minutes. ACTIQ is available in six dosage strengths to allow individualization of dosing. Side effectsof ACTIQ are typical of opioid products and include somnolence, nausea, vomiting and dizziness. The greatest risk from improper use of ACTIQ, as withall opioid based products, is the potential for respiratory depression, which can be life threatening. We market ACTIQ under a comprehensive riskmanagement program of educational and safe use messages that inform health care professionals, patients and their families of proper use, storage, handlingand disposal of the product. The FDA has notified us that we must implement a REMS Program for ACTIQ and generic OTFC. We submitted our REMS Program for ACTIQ and generic OTFC in early April 2009. Subject to the timing andnature of further discussions with the FDA, we expect to receive a response from the FDA by the middle of 2010.
[Competition]
FENTORA/ACTIQ/Generic OTFC: Both long acting and short acting formulations are prescribed to treat cancer pain. Persistent pain is typicallytreated by around the clock administration of long or short acting opioids. Breakthrough cancer pain is usually treated with a short acting product, suchas FENTORA, ACTIQ or generic OTFC, that is used in conjunction with an around the clock formulation.
Long acting products, which have a slower onset and longer duration of action relative to FENTORA, ACTIQ and generic OTFC, are commonlyprescribed to treat persistent pain. Three long acting opioid analgesics and their generic equivalents currently marketed for chronic pain dominate thismarket: Johnson & Johnson's DURAGESIC® and Purdue Pharmaceuticals' OXYCONTIN® and MS CONTIN®. Persistent cancer pain also is treated withshort acting opioid tablets, capsules and elixirs, as well as quick acting invasive opioid delivery systems (i.e., intravenous, intramuscular andsubcutaneous), many of which have been available for many years and are available in inexpensive generic form.
The overwhelming majority of prescriptions written to treat breakthrough cancer pain are for short acting opioids other than FENTORA, ACTIQ orgeneric OTFC, such as morphine and combination products (with acetaminophen and oxycodone or hydrocodone), as well as quick acting opioidsdelivered via invasive delivery systems. In some cases, physicians also may attempt to manage breakthrough pain by increasing the dose of a long actingopioid.
We are aware of numerous companies developing other technologies for rapid delivery of opioids to treat breakthrough pain, including transmucosal,transdermal, nasal spray, and inhaled delivery systems, among others. If these technologies are successfully developed and approved over the next fewyears, they could represent significant competition for FENTORA, ACTIQ and generic OTFC. The existence of generic OTFC has and will likely continue to impact sales of ACTIQ and could negatively impact the growth of FENTORA. Since thelaunch of generic OTFC in September 2006, ACTIQ sales have been meaningfully eroded. In addition, sales of our own generic OTFC could besignificantly impacted by the entrance into the market of additional generic OTFC products, which could occur at any time. For example, we expect Covidien to enter the U.S. market with its generic OTFC in the first quarter of 2010.
【2006】
Our second most significant product in 2006 was ACTIQ(R) (oral transmucosal fentanyl citrate) [C-II], which comprised approximately 34% of our total consolidated net sales for the year ended December 31, 2006, of which approximately 95% was in the U.S. market. In late September 2006, Barr Laboratories, Inc. entered the U.S. market with a generic version of ACTIQ (“generic OTFC”) pursuant to our license and supply agreement. As a result, ACTIQ sales have been meaningfully eroded by generic OTFC products sold by Barr and by us through our sales agent, Watson Pharmaceuticals, Inc., and we expect this erosion will continue during 2007.
With respect to ACTIQ, the U.S. patents covering the currently marketed compressed powder pharmaceutical composition and methods for administering fentanyl via this composition expired on September 5, 2006. Corresponding patents in foreign countries are set to expire between 2009 and 2010. Our patent protection with respect to the ACTIQ formulation we sold prior to June 2003 expired in May 2005.
Under two separate agreements with Barr Laboratories, Inc., we licensed to Barr our U.S. rights to any intellectual property related to ACTIQ. The rights we granted to Barr became effective on September 5, 2006 and Barr entered the market with generic OTFC on September 27, 2006. As a result, ACTIQ sales have been meaningfully eroded and we expect this erosion will continue during 2007. Moreover, sales of our own generic OTFC could be significantly impacted by the entrance into the market of additional generic OTFC products, which could occur at any time.ACTIQ is approved in the United States for the management of breakthrough cancer pain in opioid tolerant patients. It was approved by the FDA in November 1998 and was launched in the United States in March 1999. Following our acquisition of Anesta Corp. in October 2000, we relaunched ACTIQ in February 2001. In October 2002, we reacquired rights to ACTIQ in 12 countries, principally in Europe, from Elan Pharma International Limited.
ACTIQ uses an oral transmucosal delivery system (“OTSR”) to deliver fentanyl citrate, a powerful, Schedule II opioid analgesic. The OTS delivery system consists of a drug matrix that is mounted on a handle. It is designed to achieve rapid absorption of fentanyl through the oral mucosa and into the bloodstream, with pain relief that may begin within 15 minutes. ACTIQ is available in six dosage strengths to allow individualization of dosing. Side effects of ACTIQ are typical of opioid products and include somnolence, nausea, vomiting and dizziness. The greatest risk from improper use of ACTIQ, as with all opioid-based products, is the potential for respiratory depression, which can be life-threatening. We market ACTIQ under a comprehensive risk management program of educational and safe use messages that inform health care professionals, patients and their families of proper use, storage, handling and disposal of the product.
To secure FTC clearance of our acquisition of CIMA LABS INC., we agreed to license to Barr our U.S. rights to intellectual property necessary to manufacture and market a generic OTFC. The rights we granted to Barr became effective on September 5, 2006 and Barr entered the United States market with generic OTFC on September 27, 2006. On this same date, we also entered the market with a generic OTFC. We are utilizing Watson as our sales agent in this effort. As a result, ACTIQ sales have been meaningfully eroded by generic OTFC products sold by Barr and by us through Watson and we expect this erosion will continue during 2007.
Under our agreement with Barr, we also agreed to sell to Barr generic OTFC for resale in the United States until the earlier of such time that Barr is able to gain FDA approval of its ANDA or September 2009. Barr has invoked this supply option and we have been manufacturing generic OTFC for Barr since the launch of the product in September 2006. Under the agreement, we are responsible for delivering bulk units to Barr and Barr is responsible for all packaging and labeling of the product. In addition, we have agreed to forbear from asserting any remaining patent rights in ACTIQ against other parties beginning on March 5, 2007.
Intellectual Property Position
FENTORA: We own patents and/or patent applications covering formulation, method of treatment and manufacturing for FENTORA expiring between 2019 and 2024. Upon FDA approval for this product, we also received a three-year period of marketing exclusivity that extends until September 2009. We also hold rights to the FENTORA trademark.
ACTIQ: The U.S. patents covering the currently approved compressed powder pharmaceutical composition and the method for administering fentanyl via this composition expired in September 2006. As described above, we have licensed to Barr our U.S. rights to intellectual property necessary to manufacture and market a generic OTFC. Corresponding patents covering the current formulation of ACTIQ in foreign countries generally expire between 2009 and 2010. Our patent protection with respect to the ACTIQ formulation we sold in the United States prior to June 2003 expired in May 2005.
★FENTORA(TM) (fentanyl buccal tablet) /ACTIQ/Generic OTFC【2010】
FENTORA and ACTIQ (including our generic version of ACTIQ ("generic OTFC")) together comprised 13% and 17% of our total consolidated net sales for the year ended December 31, 2010 and 2009, respectively, of which 75% and 80% were in the U.S. market, respectively.
★ACTIQ/Generic OTFC【2010】
ACTIQ is approved in the United States and certain countries in Europe for the management of breakthrough cancer pain in opioid-tolerant patients. Generic OTFC is the generic version of ACTIQ sold through our sales agent, Watson Pharmaceuticals, Inc. in the United States. The FDA has notified us that we must implement a REMS Program for ACTIQ and generic OTFC. Subject to the timing and nature of further discussions with the FDA, we expect to receive a response from the FDA in the first half of 2011. ACTIQ sales have been meaningfully eroded by the launch of FENTORA and other fentanyl-based products and by generic OTFC products sold since June 2006.
★FENTORA(TM) (fentanyl buccal tablet)【2010】
We received U.S. Food and Drug Administration ("FDA") approval of FENTORA in late September 2006 and launched the product in the United States in early October 2006. FENTORA is indicated for the management of breakthrough pain in patients with cancer who are already receiving and are tolerant to opioid therapy for their underlying persistent cancer pain and was launched in October 2006. In April 2008, we received marketing authorization from the European Commission for EFFENTORA for the same indication as FENTORA and launched the product in certain European countries in January 2009.We have focused our clinical strategy for FENTORA on studying the product in opioid-tolerant patients with breakthrough pain associated with chronic pain conditions, such as neuropathic pain and back pain. In November 2007, we submitted a supplemental new drug application ("sNDA") to the FDA seeking approval to market FENTORA for the management of breakthrough pain in opioid tolerant patients with chronic pain conditions. In December 2008, we received a supplement request letter from the FDA requesting that we submit a Risk Evaluation and Mitigation Strategy (the "REMS Program") with respect to FENTORA. We have been engaged in ongoing discussions with the agency regarding our REMS program for FENTORA and ACTIQ, and we expect to receive a response from the FDA in the first half of 2011. We believe that, by working with the FDA, we can design and implement a REMS Program to meet the FDA's requests and possibly to provide a potential avenue for approval of the sNDA. We anticipate initiating the REMS Program upon receipt of approval from the FDA.
In clinical trials, FENTORA was generally well tolerated. Most adverse events occurring with FENTORA are typical opioid side effects. The most serious adverse events associated with all opioids are respiratory depression (potentially leading to apnea or respiratory arrest), circulatory depression, hypotension, and shock. The most common (greater or equal to 10 percent) adverse events observed in clinical trials of FENTORA in patients with cancer were nausea, vomiting, application site abnormalities, fatigue, anemia, dizziness, constipation, edema, asthenia, dehydration, and headache. In clinical trials in patients with other chronic pain conditions, the most common (greater or equal to 10 percent) adverse events were nausea, vomiting, back pain, dizziness, headache, and somnolence. Application site adverse events were reported in 12 percent of patients. Most side effects were mild to moderate in severity.
【2006】
During 2006, two of our products were approved by the U.S. Food and Drug Administration (the “FDA”). In late September 2006, we received FDA approval of our next-generation proprietary pain product, FENTORA(TM) (fentanyl buccal tablet) [C-II], and launched the product in the United States in early October. FENTORA is indicated for the management of breakthrough pain in patients with cancer who are already receiving and are tolerant to opioid therapy for their underlying persistent cancer pain. We are focusing our longer-term clinical strategy on developing FENTORA for patients with breakthrough pain associated with other conditions, including neuropathic pain and back pain. In October 2006 and January 2007, we announced that data from Phase 3 clinical trials of FENTORA demonstrated efficacy in the management of breakthrough pain in opioid-tolerant patients with chronic low back pain and chronic neuropathic pain, respectively. Pending positive data from an ongoing study in patients with non-cancer breakthrough pain, our goal is to submit a supplemental new drug application (“sNDA”) to the FDA in late 2007. This sNDA would seek to expand the labeled indications for FENTORA beyond breakthrough pain in patients with cancer.
We received FDA approval of FENTORA in late September 2006 and launched the product in the United States in early October. FENTORA is indicated for the management of breakthrough pain in patients with cancer who are already receiving and are tolerant to opioid therapy for their underlying persistent cancer pain. FENTORA is the first and only buccal tablet approved for this indication.
FENTORA delivers fentanyl, a powerful, Schedule II opioid analgesic, through the oral mucosa (the lining of the mouth) utilizing our proprietary, enhanced absorption technology, ORAVESCENTR. The sugar-free FENTORA tablet is placed between the upper cheek and gum above a rear molar tooth. When it comes into contact with saliva, FENTORA’s delivery system generates a reaction leading to the release of carbon dioxide. It is believed that transient pH changes accompanying this reaction may optimize how well the tablet dissolves and how quickly the medicine passes across the buccal mucosa.
In clinical trials, FENTORA was generally well tolerated. Most adverse events occurring with FENTORA are typical opioid side effects. The most serious adverse events associated with all opioids are respiratory depression (potentially leading to apnea or respiratory arrest), circulatory depression, hypotension, and shock. The most common (greater than or equal to 10 percent) adverse events observed in clinical trials of FENTORA were nausea, vomiting, application site abnormalities, fatigue, anemia, dizziness, constipation, edema, asthenia, dehydration and headache. Most side effects were mild to moderate in severity.
We are focusing our longer-term clinical strategy on developing FENTORA for patients with breakthrough pain associated with other conditions, including neuropathic pain and back pain. In October 2006 and January 2007, we announced that data from Phase 3 clinical trials of FENTORA demonstrated efficacy in the management of breakthrough pain in opioid-tolerant patients with chronic low back pain and chronic neuropathic pain, respectively. Pending positive data from an ongoing study in patients with non-cancer breakthrough pain, our goal is to submit a sNDA to the FDA in late 2007. This sNDA would seek to expand the labeled indications for FENTORA beyond breakthrough pain in patients with cancer.
★AMRIX [持続性Cyclobenzaprine HCl]骨格筋弛緩剤 【2010】AMRIX is approved in the United States for short-term use as an adjunct to rest and physical therapy for relief of muscle spasm associated with acute, painful musculoskeletal conditions and was launched in November 2007. With convenient, once-daily dosing, AMRIX provides relief from muscle spasm comparable to that with cyclobenzaprine hydrochloride taken three times daily. AMRIX is intended for use up to two or three weeks. The most common side effects of AMRIX in Phase III clinical trials were dry mouth, dizziness, fatigue, constipation, nausea and dyspepsia.
★VIVITROL(TM) (naltrexone for extended-release injectable suspension) [2006]In April 2006, the FDA approved VIVITROL(TM) (naltrexone for extended-release injectable suspension), and we launched the product in June. VIVITROL is indicated for the treatment of alcohol dependent patients who are able to abstain from alcohol in an outpatient setting and are not actively drinking when initiating treatment. Treatment with VIVITROL should be used in combination with psychosocial support, such as counseling or group therapy. Under the license and collaboration agreement we signed with Alkermes, Inc. in June 2005, Alkermes is responsible for manufacturing commercial supplies of VIVITROL and we have primary responsibility for the marketing and sale of the product.★GABITRIL(R) (tiagabine hydrochloride) *Cephalon Inc.はGabitril販売権をSanofi-Synthelaboから$20.5 million で譲受。 2001.1にAbbott社から、米国のGabitril販売権を譲受している。Gabitrilの販売高は、 推定$27 million (2001) Cephalon Strengthens Its Global Presence By Acquiring International Rights to GABITRIL[2002.1.8] - GABITRIL(R) (tiagabine hydrochloride)のexpanded rightをSanofi-Synthelabo and Novo Nordisk A/Sから買収。 地域は、カナダ・中南米・日本を除く全世界。 Cephalonは2001.1 Abbott社から米国の販売権のサブライセンスを獲得。 GABITRILは現在２３か国で販売、２５か国で承認待ち。[2010]
GABITRIL is a selective GABA (gamma-aminobutyric acid) reuptake inhibitor approved for use as adjunctive therapy in the treatment of partial seizures in epileptic patients. We currently have worldwide product rights to GABITRIL, excluding Canada and Latin America, and we market GABITRIL in the United States, France, the United Kingdom and Germany, among other countries. The first of four Orange Book-listed patents for GABITRIL is set to expire in September 2011, and we could face generic competition at that time. As a result, GABITRIL sales may materially decline.[2006]
GABITRIL is a selective GABA (gamma-aminobutyric acid) reuptake inhibitor approved for use as adjunctive therapy in the treatment of partial seizures in epileptic patients. Epilepsy is a chronic disorder characterized by seizures that cause sudden, involuntary, time-limited alteration in behavior, including changes in motor activities, autonomic functions, consciousness or sensations, and accompanied by an abnormal electrical discharge in the brain. We currently have worldwide product rights to GABITRIL, excluding Canada and Latin America, and we market GABITRIL in the United States, France, the United Kingdom and Germany, among other countries. We have one third-party manufacturer of the active drug substance in GABITRIL and finished commercial supplies of the product in the United States and one third-party manufacturer of the active drug substance and finished commercial supplies outside the United States.While applicable laws and regulations prevent us from promoting our products for uses beyond those contained in the approved label, our analysis of prescription data in the United States for GABITRIL indicates that many physicians have elected to prescribe the product to treat conditions outside of its currently labeled indication. In February 2005, working with the FDA, we updated our prescribing information for GABITRIL to include a bolded warning describing the risk of new onset seizures in non-induced patients without epilepsy. Following this update, we actively communicated this risk to physicians and otherwise limited our sales and marketing efforts for GABITRIL. These actions have led to a decrease in prescriptions and sales of GABITRIL.
In June 2006, we announced that data from our Phase 3 clinical program evaluating GABITRIL for the treatment of generalized anxiety disorder (“GAD”) did not reach statistical significance on the primary study endpoints. We have no plans to continue further study of GABITRIL for the treatment of GAD or any other disease or disorder.
Intellectual Property Position
GABITRIL is our trademark that is used in connection with pharmaceuticals containing tiagabine as the active drug substance. This product is covered by U.S. and foreign patents that are held by Novo-Nordisk A/S. The U.S. patents have been licensed in the United States exclusively to Abbott Laboratories. We have an exclusive sublicense from Abbott to these patents in the United States and exclusive licenses from Novo-Nordisk to corresponding foreign patents.
There are four U.S. composition-of-matter patents covering the currently approved product: a patent claiming tiagabine, the active drug substance in GABITRIL; a patent claiming crystalline tiagabine hydrochloride monohydrate and its use as an anti-epileptic agent; a patent claiming the pharmaceutical formulation and a patent claiming anhydrous crystalline tiagabine hydrochloride and processes for its preparation. These patents currently are set to expire in 2011, 2012, 2016 and 2017, respectively. Supplemental Protection Certificates based upon corresponding foreign patents covering this product are set to expire in 2011. We also hold rights to the GABITRIL trademark.
●The following is a summary of the most significant products we market and sell in Europe as of December 31, 2010:(1) ABELCET is licensed from Bristol Myers Squibb. (2) Marketed under the name MODIODAL(R) (modafinil) in France and under the name VIGIL(R) (modafinil) in Germany. (3) TARGRETIN is licensed from Ligand Pharmaceuticals. (4) NAXY and MONO-NAXY are licensed from Abbott France. In Asia, we have established an office in Hong Kong. We are seeking approval from the Chinese authorities to develop and register our products and are exploring opportunities in China and expect this market to be a key part of our Asian growth strategy moving forward. In 2007, our licensees, Alfresa Pharma and Mitsubishi Tanabe Pharma, launched modafinil in Japan (under the trade name MODIODAL) for the treatment of excessive daytime sleepiness associated with narcolepsy. Nippon Shinyaku launched TRISENOX (arsenic trioxide) in Japan in 2004. We have formed relationships with other Japanese companies that are conducting clinical trials with, and pursuing regulatory approval of, a number of our products in Japan. Cephalon recently received marketing approval for TREANDA in Hong Kong, and we will be responsible for the marketing of the product in Hong Kong.
Product Indication Key Market(s) ABELCET (amphotericin B lipid complex)(1) Anti-fungal France, Germany, Italy, Spain, U.K.,Central Eastern European countries, Benelux, Poland ACTIQ (oral transmucosal fentanyl citrate) Breakthrough cancer pain France, Germany, U.K.,Italy, Netherlands,Spain DICLOFENAC Non-steroidal anti-inflammatory drug(NSAID) Switzerland, Africa, Middle East, Poland EFFENTORA Breakthrough cancer pain France, Germany, Italy, Poland, Spain, U.K. MYOCET (liposomal doxorubicin) Late stage breast cancer France, Germany, Italy, Spain, U.K.,Central Eastern European Countries, Benelux, Poland OMEPRAZOL Proton pump inhibitor for indigestion Switzerland, Portugal, Baltic countries PROVIGIL (modafinil)(2) Excessive sleepiness associated with narcolepsy and certain other conditions France, Germany, U.K. SPASFON(R) (phloroglucinol) Biliary/urinary tract spasm and irritable bowel syndrome France TARGRETIN (bexarotene)(3) Cutaneous T-cell lymphoma France, Germany, U.K. VOGALENE(metopimazine) Nausea France ●旧製品 FONZYLANE(R) (buflomedil) Cerebral vascular disorders France GABITRIL (tiagabine hydrochloride) Partial seizures France, Germany, U.K. NAXY(R) and MONO-NAXY(R) (clarithromycin)(4) Antibiotic France In April 2008, we received marketing authorization from the European Commission for EFFENTORA for the same indication as FENTORA and launched the product in certain European countries in January 2009. We anticipate launching EFFENTORA in additional European countries in 2011.
In December 2009, we entered into an agreement with UCB Pharma France under which we acquired all assets related to the development, manufacturing, marketing and sale of VOGALENE® (metopimazine) and VOGALIB® (metopimazine) in France and French overseas territories for $53.3 million. These products are approved for use in the symptomatic treatment of nausea and vomiting. The injectable solution is approved for the prevention of nausea and vomiting in patients under chemotherapy.
In February 2011, we entered an agreement with H. Lundbeck A/S for the distribution of certain of our proprietary products in Latin America and Canada.
In early 2006, we and Novartis agreed to terminate our exclusive collaboration arrangement established in November 2000. Under this collaboration agreement, we had marketed PROVIGIL, TEGRETOLR (carbamazepine), RITALIN(R) (methylphenidate), ANAFRANIL(R) (clomipramine) and LIORESAL(R) (baclofen) in the United Kingdom and had shared with Novartis the earnings from sales of the four Novartis products and PROVIGIL in the United Kingdom.
■パイプライン /2011.3
製品 適応症 ステージ 発売目標年 オリジン 備考 x TREANDA(bendamustine HCl) 【適応追加 】 Front line NHL Phase III 2012 旧東独Jenapharm社創薬;北米権Salmedix, Inc(2005.6買収) 日本トレアキシン[エーザイ] x Tamper deterrent hydrocodone Chronic Pain Phase III 2012 自社 Our tamper-deterrent formulation of hydrocodone was developed from our efforts to create tamper deterrent opioids utilizing our OraGuard technology. OraGuard provides resistance against various tampering methods, including chewing, aqueous extraction for IV dosing and alcohol extraction. ▼ NUVIGIL[armodafinil] 【適応追加 】 Adjunctive therapy for treating bi-polar depression disorder in adults Phase III 2013 自社 日本未開発 ○ Mesenchymal precursor cells Cord blood expansion Phase II completed 2014 Mesoblast Limited (2010.12戦略・資本提携) In December, 2010, we entered into a strategic alliance with Mesoblast Limited ("Mesoblast") to develop and commercialize novel adult Mesenchymal Precursor Stem Cell (MPC) therapeutics for degenerative conditions of the cardiovascular and central nervous systems. These conditions include Congestive Heart Failure, Acute Myocardial Infarction, Parkinson's Disease, and Alzheimer's Disease. The alliance also extends to products for augmenting hematopoietic stem cell transplantation in cancer patients. As part of the development and commercialization agreement, in exchange for exclusive world-wide rights to commercialize specific products based on Mesoblast's proprietary adult stem cell technology platform, we agreed to pay Mesoblast a nonrefundable up front payment of $130 million. In December 2010, we paid $100.0 million, which was expensed as acquired in process research and development expense. On or about February 11, 2011, we will also and expense, as acquired in process research and development expense, the remaining $30 million of upfront fees as part of the collaboration agreement we have received Mesoblast shareholder and regulatory approval for us to purchase additional shares, as agreed to under our share purchase agreement.
Additionally, we made a $133.9 million equity investment in Mesoblast common stock, representing a 12.2% interest in the company, included in noncurrent assets on our consolidated balance sheet. At the date of acquisition, we believe we exercise significant influence over the company due to contractual agreements in place for us to increase our ownership to 19.99% in early 2011, our Chief Executive Officer holding a voting seat on the Mesoblast Board of Directors and the existence of various revenue arrangements between us and Mesoblast. Therefore, we consider our investment in Mesoblast to be an equity method investment. We have elected to account for our equity method investment under the fair value option. We measured the fair value of our investment at date of acquisition and prospectively utilizing the company's publicly traded stock price. On the date we acquired the 12.2% interest, Mesoblast's share price was Australian dollar ("A$") A$3.43 and the fair value of our investment was $105.4 million. We recorded the difference between the consideration paid and fair value at the date of acquisition as a change in fair value of investments within other income (expense) on the statement of operations. On December 31, 2010, Mesoblast's share price was A$4.67 and we remeasured the fair value of our investment at $145.9 million. The change in fair value between the date of acquisition and the balance sheet date was also recorded as a change in fair value of investments within other income (expense) on the consolidated statement of operations. We consider Mesoblast a related party.
Shareholder approval occurred on February 9, 2011 and we anticipate receiving an additional 7.8% of Mesoblast shares and making the associated payment of approximately $108 million on or about February 11, 2011.
With respect to each product the Company chooses to commercialize, Mesoblast could receive up to $1.7 billion upon the achievement of certain regulatory milestones. The $1.7 billion of milestone payments is estimated based on the approval of the product for the treatment of ten indications in various territories. Mesoblast will be responsible for the conduct and expenses of certain Phase IIa clinical trials and commercial supply of the products. Cephalon will be responsible for the conduct and expenses of all Phase IIb and III clinical trials and subsequent commercialization of the products. If the products are commercially sold, Mesoblast will retain all manufacturing rights and will receive a percentage of net product sales
○ CEP-37247 (次世代のanti-tumor necrosis factor) Sciatica (administered via epidural injection) Phase I/II 2014 Arana Therapeutics Limited(2009.2.27買収) CEP-37247 is a new generation tumor necrosis factor (TNF) alpha blocker in Phase II development to treat patients with sciatica. Sciatica is a neuropathic inflammatory pain condition that occurs when the sciatic nerve is compressed, injured or irritated. CEP-37247 is based on a new type of therapeutic protein called a domain-based antibody. CEP-37247 is the first product incorporating domain-based antibodies (dAb) to be used in human trials. Domain-based antibodies exhibit the binding properties to a target characteristic of a full-sized antibody, but are considerably smaller. This smaller size has several possible advantages including improved manufacturing yield, lower immunogenicity and improved tissue penetration. In November 2010, we exercised our option to acquire BioAssets Development Corporation ("BDC"), following receipt of interim data from a Phase II placebo-controlled proof-ofconcept study evaluating epidural administration of the TNF inhibitor, etanercept, for the treatment of sciatica in 45 patients. As part of the acquisition, we gained the rights to the BDC intellectual property estate covering the use of cytokine inhibitors, including TNF inhibitors, for sciatic pain in patients with intervertebral disk herniation, as well as other spinal disorders. ▼ CINQUIL(reslizumab) Eosinophilic asthma(好酸球性喘息) Phase III 2014 Ception Therapeutics, Inc.(2009.1買収) 重症な喘息だが、患者数は少ない。 CINQUIL is an investigational humanized monoclonal antibody (mAb) against interleukin-5 (IL-5) in Phase III development to treat eosinophilic asthma. IL-5 has been shown to play a crucial role in the maturation, growth and chemotaxis (movement) of eosinophils, inflammatory white blood cells implicated in a number of allergic diseases. Eosinophilic asthma is a type of severe asthma with persistent inflammation of the airways associated with increased levels of eosinophils. There is an increasing body of evidence that asthma is a heterogeneous disease, with eosinophilic airway inflammation a common feature among phenotypes. Many patients with asthma respond well to inhaled corticosteroids. However, there is a subgroup of patients with severe asthma in whom eosinophilic airway inflammation persists despite therapy with high doses of inhaled corticosteroids. Patients with eosinophilic asthma may experience changes in their airways, impaired lung function, more frequent asthma exacerbations, and near-fatal asthma attacks. Such patients are in need of additional anti-inflammatory therapies to address persistent high levels of eosinophils and associated poor prognosis. In February 2010, we announced that a Phase II clinical trial of CINQUIL in 106 patients demonstrated improved asthma control in adult patients with moderate to severe asthma and eosinophilic airway inflammation, as measured by the primary study endpoint, a change in Asthma-Control-Questionnaire or ACQ score (p=0.054). In addition, an analysis of the FEV1, a measure of lung function, showed a statistically significant improvement with CINQUIL compared to placebo (p=0.002).
○ LUPUZOR Systemic lupus erythematosus Phase IIb 2015 ImmuPharma PLC(2008.11世界独占権獲得) We hold an exclusive, worldwide license to the investigational medication LUPUZOR for the treatment of systemic lupus erythematosus ("Lupus"). Under the terms of our license, we will assume all expenses for the additional Phase II and Phase III clinical studies, regulatory filings and, assuming regulatory approval, subsequent commercialization of the product. Lupus is an autoimmune disease causing various effects throughout different parts of the body. Its severity can range from very mild to extremely serious depending on which body organs are afflicted. The Lupus Foundation of America estimates that 1.5 million Americans have a form of Lupus. Approximately 90 percent of those diagnosed with the disease are women. Lupus is two to three times more prevalent among people of color, including African-Americans, Hispanics/Latinos, Asians, and Native Americans. LUPUZOR has shown that it modulates, through a unique mechanism, a specific subset of CD4 T cells which may play a critical role in the physiopathology of Lupus. Patents for LUPUZOR have been approved in Europe, Japan and Australia, and have been applied for in the United States.
In May 2010, our licensor Immupharma plc announced the final results from a Phase IIb trial of LUPUZOR in active patients with Lupus. LUPUZOR administered at 200 mcg once-a-month for 3 months plus standard of care achieved a clinically significant improvement in patient response rate versus standard of care plus placebo in the intention to treat (ITT) analysis. The improvement was statistically significant in a subgroup (90% of the ITT population) of moderate to severe patients. Sixty-two percent of this sub-group of patients were responders according to both a composite clinical score and a decrease of 4 points of the SLEDAI score when treated with LUPUZOR 200 mcg once-a-month for three months compared to 41% on placebo. LUPUZOR was generally well tolerated with fewer serious adverse event rates versus standard of care leading to discontinuation.
▼ REVASCOR Congestive heart failure Phase II 2015 Mesoblast Limited (2010.12戦略・資本提携) Acute myocardial infarction Phase II 2016 Cephalon and Mesoblast have entered into a strategic alliance to develop and commercialize Mesoblast's Mesenchymal Precursor Cell (MPC) therapeutics for hematopoietic stem cell transplantation in cancer patients, as well as degenerative conditions of the cardiovascular and central nervous systems, including congestive heart failure, acute myocardial infarction, Parkinson's Disease, and Alzheimer's Disease. Human stem cells are the immature cells that give rise to all of the different types of mature cells that make up the organs and tissues of the adult body.
Mesoblast MCPs are derived from volunteer adult donors. MPCs from a given donor do not activate immune cells from unrelated recipients. This property is likely to enable Cephalon and Mesoblast to generate a range of "off-the-shelf" MPC products from universal donors, simplifying the process and costs of batch quality assurance/quality control testing, reducing cost-of-goods, and increasing product margins. It is anticipated that MPC-derived products from allogeneic, or unrelated, donors will be available to the clinician on demand, and used in a similar way as any pharmaceutical product. Unlike embryonic stem cells, there are no ethical issues with the use of MPCs.
In January 2011, we announced with Mesoblast positive interim results from Mesoblast's ongoing multi-center Phase II trial of REVASCOR, its "off-theshelf" proprietary adult stem cell product for patients with congestive heart failure. Patients who received a single injection of REVASCOR into damaged heart muscle have had less cardiac events, deaths, and hospitalizations during the follow-up period to date than control patients. In the randomized, placebocontrolled Phase II trial in 60 patients with moderate-severe congestive heart failure, a single injection of REVASCOR at one of three progressively increasing doses has been administered to 45 patients randomized to receive cell therapy in addition to standard-of-care, while 15 control patients have been concomitantly randomized to receive standard-of-care and a sham injection. The trial will be completed when all available patients have been followed-up for 12 months. REVASCOR is delivered to damaged areas of the heart by a minimally invasive cardiac catheterization procedure performed under local anaesthesia while the patient is awake. Patients undergoing the procedure are usually released from the hospital within 24 hours.
A scheduled interim analysis of safety and of time-dependent hard efficacy endpoints was performed when the last of the 60 enrolled patients had completed six months of follow-up in December 2010. At this time point, the 45 patients who received REVASCOR had been followed for a mean of 18.5 months/patient and the 15 controls had been followed for a mean of 18 months/patient. There have been no cell-related adverse events in any of the 45 patients treated with REVASCOR, demonstrating that all three doses of the cell therapy product are safe over both the short and medium term. Analyses of time-dependent hard efficacy endpoints showed that a single injection of REVASCOR significantly reduced the number of patients who developed any serious adverse events over the follow-up period from 93.3% in the control group to 44.4% in the treated patients (p=0.001). REVASCOR also significantly reduced the number of patients who developed any major adverse cardiac events (MACE, defined as the composite of cardiac death, heart attack, or coronary revascularization procedures) from 40% to 6.7% (p=0.005). A single injection of REVASCOR reduced the overall monthly event rate of a MACE by 84% compared with controls (p=0.01), and every dose tested demonstrated a similar protective effect. Death from cardiac causes was reduced from 13.3% to 0% over this period (p=0.059) and the overall monthly rate of cardiac-related hospitalizations was reduced by 48% (p=0.07).
Congestive heart failure remains a leading cause of hospital admissions, morbidity and mortality in the Western world. The American Heart Association and the National Heart, Lung, and Blood Institute have estimated that cardiovascular disease and stroke cost the United States at least $448.5 billion annually, and the burden continues to grow as the population ages. In the United States alone, congestive heart failure has an annual incidence of 670,000 patients, a prevalence of 6.2 million patients, and causes over 1.1 million hospitalizations and 300,000 deaths per year. Heart failure affects around 10 million in Europe and as many as 20 million worldwide.
We anticipate finalizing with Mesoblast the Chemistry, Manufacturing Controls requirements during 2011 and prior to beginning any Phase III program. In 2011, we plan to finalize the Phase III protocol for a cord blood expansion clinical study, conduct an end of Phase II meeting with the FDA for the congestive heart failure clinical study and commence a Phase II program for the treatment of acute myocardial infarction
●Cephalon Inc ■Investors ●SEC Filing - FORM 10-K[2011.2.11] - [pdf] - [doc] - [xls] - FORM 10-K(2010.2.12) - [pdf] - [doc] - [xls] - FORM 10-K(2009.2.23) - [pdf] - [doc] - [xls] - FORM 10-K(2008.2.28) - [pdf] - [doc] - [xls] - FORM 10-K(2007.2.28) - [pdf] - FORM 10-K(2006.3.13) - [pdf,] - FORM 10-K(2005.3.15) - FORM 10-K(2004.3.) ●Annual Reports ●News Releases Cephalon Reports Record Sales and Adjusted Net Income for 2009[2010.2.11] Cephalon, Inc. Completes Acquisition of TRISENOX(R) From Cell Therapeutics, Inc.[2005.7.19] ●Our Science Pipeline ■Media ●News Releases:
選択 領域 製品名(主成分) 適応症(薬効) 競合 備考 ▼ 神経系 AMRIX(Cyclobenzaprine HCl Extended-release capsules) 骨格筋弛緩剤 日本未開発 x 神経系 PROVIGIL(modafinil) 睡眠障害治療薬 モディオダール錠100mg x 神経系 FENTORA(fentanyl buccal tablets) 鎮痛剤 KW-2246（フェンタニル）舌下錠(申請準備) (子会社CIMA Labs開発のOraVescent(R) drug delivery system利用) ▼ 代謝 VIVITROL(naltrexone extended-release injectable suspension) 最初で唯一の月１回投与のアルコール依存症治療薬 - Alkermes, Inc.から2005.6に米国ライセンス x 癌 Trisenox(arsenic trioxide) 骨髄性白血病 トリセノックス Cell Therapeutics, Inc.から2005.7譲受($71.9 million) x 神経系 ACTIQ(oral transmucosal fentanyl citrate) 癌疼痛用薬 KW-2246（フェンタニル）舌下錠(申請準備) x 神経系 GABITRIL(tiagabine HCl) 抗てんかん剤 日本は1998年P2中止 Novo Nordiskが1988年創製、Abbottが共同開発;Cephalonはライセンスを受けた x 感染症 ABELCET(amphotericin B lipid complex) 抗真菌剤 アムビゾーム（アムホテリシンBリポソーム） 注射剤 英・仏・独・伊・スペイン x 癌 TREANDA(bendamustine HCl) CLL(慢性リンパ性白血病) 「トレアキシン点滴静注用100 mg」 ▼ 神経系 Nuvigil(armodafinil) 閉塞性睡眠時無呼吸を伴う過眠症 日本未開発
■Theravance, Inc[米]
- http://www.theravance.com/; nasdaq:THRX 設立 Nov. 1996 under the name Advanced Medicine, Inc. in Delaware 操業開始 May 1997 現社名Theravance, Incに変更 April 2002 ●会社決算●製品
($ 000) 2009 2008 2007 2006 2005 2004 2003 2002 2001 売上高 24,374 23,096 22,002 19,587 12,054 研究開発費 77,524 82,020 155,254 166,564 137,936 一般管理費 27,066 28,861 35,313 32,193 23,674 リストラ費用 1,145 5,419 - - - 営業経費 計 105,735 116,300 190,567 198,757 161,610 営業利益 (81,361) (93,204) (168,565) (179,170) (149,556) 経常利益 当期純利益 (85,302) (93,643) (159,997) (166,044) (143,164) 従業員数[連結] 194
●telavancin[VIBATIV]cSSSI 【2009】
Our 2005 collaboration arrangement with Astellas covers the development and commercialization of VIBATIVmV, a bactericidal, once-daily injectable antibiotic developed by us for the treatment of Gram-positive infections, including methicillin-resistant Staphylococcus aureus. The U.S. Food and Drug Administration has approved VIBATIVmV for the treatment of adult patients with complicated skin and skin structure infections (cSSSI) caused by susceptible Gram-positive bacteria, including Staphylococcus aureus , both methicillinresistant (MRSA) and methicillin-susceptible (MSSA) strains. VIBATIVmV is also approved in Canada for the treatment of adult patients with cSSSI.In November 2005, we entered into a collaboration arrangement with Astellas for the development and commercialization of telavancin. In July 2006, Japan was added to our telavancin collaboration, thereby giving Astellas worldwide rights to this medicine. Through December 31, 2009, we have received $190.0 million in upfront, milestone and other fees from Astellas and we are eligible to receive up to an additional $30.0 million in remaining milestone payments related to regulatory filings and approvals in various regions of the world. Additionally, certain costs related to the collaboration are reimbursable by Astellas. In 2009 the FDA approved VIBATIV TM for the treatment of adult patients with cSSSI caused by susceptible Gram-positive bacteria, including Staphylococcus aureus , both MRSA and MSSA strains. VIBATIV TM also was approved in Canada in 2009 for the treatment of adult patients with cSSSI. We are entitled to receive royalties on global net sales of VIBATIV TM that, on a percentage basis, range from the high teens to the upper twenties depending on sales volume. We were responsible for substantially all costs to develop and obtain U.S. regulatory approval for VIBATIV TM and Astellas is responsible for substantially all costs associated with commercialization of VIBATIV TM .
In October 2009, Astellas and we announced that Astellas Pharma Europe B.V. submitted a MAA to the EMEA for telavancin for the treatment of NP, including ventilator-associated pneumonia, and complicated skin and soft tissue infections in adults (cSSTI). The EMEA has since completed the Validation Phase for the MAA and initiated the scientific review of the application.
On November 27, 2009 we announced that we received a Complete Response letter from the FDA relating to our telavancin NDA for NP, which was filed in January 2009. The Complete Response instructed us that submission of additional data and analyses for the NP patient population to support an evaluation of all-cause mortality as the primary efficacy endpoint was necessary to demonstrate the safety and efficacy of telavancin. The Phase 3 NP clinical program included clinical response as the primary efficacy endpoint, consistent with current draft FDA guidelines for antibacterial clinical trial design in NP, and all-cause mortality as a secondary endpoint. The Complete Response did not specify the time point at which the FDA will measure the all-cause mortality data, nor did it indicate the populations in which these analyses will be considered. The Complete Response letter also requested a scientific rationale for pooling the all-cause mortality data from the two studies as they may individually be of insufficient size and statistical power to support the evaluation of all-cause mortality as the primary efficacy endpoint.
We responded to the Complete Response letter in December 2009. The key elements of our response included a rationale for pooling the two Phase 3 NP studies to evaluate all-cause mortality as the primary efficacy endpoint and all available all-cause mortality data that was analyzed using Kaplan-Meier survival estimates. In January 2010 the FDA sent us a letter notifying us that it considered our response "incomplete," and stating that even if pooling of the two studies is acceptable for analyzing mortality, the two pooled studies would then equate to only one adequate and well-controlled trial and therefore would not constitute the substantial evidence of efficacy required for approval. In addition, the FDA noted that the adequacy and similarity of populations across the studies for the purposes of pooling had not yet been determined, and is still a review issue. Finally, the FDA also noted several design criteria that should be taken into account in the design of new clinical trials. These design criteria do not include a specific primary endpoint for the evaluation of efficacy, the size or number of studies required, or what the appropriate statistical analysis might be. As a result, the design, size and scope of any additional studies required by the FDA are unclear at this time. With regard to our telavancin NP NDA, we believe that the FDA's position is that it will require data from an additional clinical study or studies before it will consider the NP NDA for approval and we do not currently intend to conduct any such studies.
【2009 競合】
VIBATIVmV competes with vancomycin, a generic drug that is manufactured by a variety of companies, as well as other drugs targeted at Gram-positive bacterial infections. Currently marketed products include but are not limited to daptomycin (marketed by Cubist Pharmaceuticals), linezolid (marketed by Pfizer) and tigecycline (marketed by Wyeth). To effectively compete with these medicines, and in particular with the relatively inexpensive generic option of vancomycin, we and our partner Astellas will need to demonstrate to physicians that, based on experience, clinical data, side-effect profiles and other factors, VIBATIVmV is preferable to vancomycin and other existing or subsequently-developed anti-infective drugs in certain clinical situations.●[RELOVAIR]COPD/喘息 【2009】
We have entered into collaboration arrangements with GSK and Astellas for the development and commercialization of our product candidates. In November 2002 we entered into our long-acting beta 2 agonist (LABA) collaboration with GSK to develop and commercialize a once-daily LABA product candidate both as a single-agent new medicine for the treatment of chronic obstructive pulmonary disease (COPD) and as part of a new combination medicine with an inhaled corticosteroid (ICS) for the treatment of asthma and/or a long-acting muscarinic antagonist (LAMA) for COPD. This collaboration is now known as the RELOVAIRmV program. In March 2004 we entered into a strategic alliance agreement with GSK under which GSK received an option to license exclusive development and commercialization rights to product candidates from all of our full drug discovery programs initiated prior to September 1, 2007, on pre-determined terms and on an exclusive, worldwide basis.In November 2002, we entered into our long-acting beta 2 agonist (LABA) collaboration with GSK to develop and commercialize a oncedaily LABA product candidate both as a single-agent new medicine for the treatment of COPD and as part of a new combination medicine with an ICS for the treatment of asthma and/or a LAMA for COPD. These programs, now known collectively as the RELOVAIR TM program, are aimed at developing next generation respiratory products to replace GSK's Seretide and Advair franchise, which reported 2009 sales of approximately $8.0 billion. Each company contributed four LABA product candidates to the collaboration.
In connection with the RELOVAIR TM program, in 2002 we received from GSK an upfront payment of $10.0 million and sold to an affiliate of GSK shares of our Series E preferred stock for an aggregate purchase price of $40.0 million. In addition, we were eligible to receive up to $495.0 million in development, approval, launch, and sales milestones and royalties on the sales of any product resulting from this program. Through December 31, 2009, we have received a total of $60.0 million in upfront and development milestone payments. GSK has determined to focus the collaboration's resources on the development of the lead LABA, GW642444 ('444), a GSK-discovered compound, together with GSK's ICS, fluticasone furoate (FF). Accordingly, we do not expect to receive any further milestone payments from the RELOVAIR TM program. In the event that a LABA product candidate discovered by GSK is successfully developed and commercialized, we will be obligated to make milestone payments to GSK which could total as much as $220.0 million if both a single-agent and a combination product were launched in multiple regions of the world. Based on available information, we do not estimate that a significant portion of these potential milestone payments to GSK are likely to be made in the next two years. Moreover, we are entitled to receive the same royalties on sales of medicines from the RELOVAIR TM program, regardless of whether the product candidate originated with Theravance or with GSK.
Theravance is entitled to annual royalties of 15% on the first $3.0 billion of annual global net sales and 5% for all annual global net sales above $3.0 billion. Sales of single-agent LABA medicines and combination medicines would be combined for the purposes of this royalty calculation. For other products combined with a LABA from the RELOVAIR TM program, such as a combination LABA/LAMA medicine, which are launched after a LABA/ICS combination medicine, royalties are upward tiering and range from the mid-single digits to 10%. However, if GSK is not selling a LABA/ICS combination product at the time that the first other LABA combination is launched, then the royalties described above for the LABA/ICS combination medicine are applicable.
【2009 競合】
We anticipate that, if approved, any product from our RELOVAIR TM program with GSK will compete with a number of approved bronchodilator drugs and drug candidates under development that are designed to treat asthma and COPD. These include but are not limited to salmeterol and fluticasone (marketed by GSK), formoterol (marketed by a number of companies) and formoterol and budesonide as a combination (marketed by AstraZeneca), and tiotropium (marketed by Boehringer Ingelheim and Pfizer). Indacaterol is being developed as a single-agent by Novartis and, in combination with an ICS (mometasone). In addition, indacaterol combined with a muscarinic antagonist is being developed by Novartis. New combinations of formoterol with fluticasone or mometasone are being developed by Abbott (with SkyePharma), and Merck respectively. Boehringer-Ingelheim is developing a combination product with tiotropium and the long-acting beta agonist BI-1744 for the treatment of COPD. In addition, several firms are reported to be developing new formulations of salmeterol-fluticasone and formoterol-budesonide which may be marketed as generics or branded generics relative to the innovator products from GSK and AstraZeneca respectively. However, the ability of such generics to achieve fully substitutable status is uncertain as there is no well established regulatory pathway for demonstration of bioequivalence for inhaled medicines. All of these efforts represent potential competition for any product from our RELOVAIR TM program.● 【2009】
●Theravance, Inc ●Products www.VIBATIV.com ■Investor Relations ●SEC Filings 10-K annual report[2010.2.26] - [pdf,119p] - [doc] - [xls] ●Press Releases
Theravance Reports Fourth Quarter and Full Year 2009 Financial Results[2010.2.11]
Theravance Announces Receipt of Additional FDA Communication Regarding Telavancin NDA for the Treatment of Nosocomial Pneumonia[2010.1.28]
Theravance Announces That EMEA Has Completed the Validation Phase for the Telavancin MAA for the Treatment of Nosocomial Pneumonia and Complicated Skin and Soft Tissue Infections[2009.11.30]
Theravance Receives Complete Response Letter on the Telavancin NDA for the Treatment of Nosocomial Pneumonia[2009.11.27]
Theravance and Astellas Announce the Commercial Launch of VIBATIV( TM ) (telavancin) in the United States[2009.11.5]
Astellas and Theravance Announce Submission of Telavancin MAA for the Treatment of Nosocomial Pneumonia and Complicated Skin and Soft Tissue Infections in Europe[2009.10.28]
Theravance Earns $20 Million Milestone Under Telavancin Collaboration Agreement[2009.10.22]
Astellas and Theravance Announce Approval of VIBATIV(TM) (telavancin) in Canada for the Treatment of Complicated Skin and Skin Structure Infections[2009.10.1]
Theravance and Astellas Announce FDA Approval of VIBATIV(TM) (telavancin) for the Treatment of Complicated Skin and Skin Structure Infections[2009.9.11]
FDA Accepts for Review Theravance's Complete Response Submission for Telavancin for the Treatment of Complicated Skin and Skin Structure Infections[2009.4.24]
Theravance Announces FDA Acceptance of Telavancin NDA for the Treatment of Hospital-Acquired Pneumonia[2009.4.6]
Theravance Receives Complete Response Letter on the Telavancin New Drug Application for the Treatment of cSSSI[2009.2.26]
Theravance Submits U.S. NDA for Telavancin for the Treatment of Hospital-Acquired Pneumonia[2009.1.26]
Theravance Reports Favorable Outcome of FDA Advisory Committee Meeting on Telavancin for the Treatment of Complicated Skin and Skin Structure Infections[2008.11.19]
■Tillotts Pharma AG[SZ]
- http://www.tillots.com/ ; ティロッツ社; 消化器病薬専門メーカー 1963 設立。 Tillotts Laboratories Limitedとして英国に。生薬系消化器潰瘍治療薬の販売 1970年代 消化器系Asacol, Colperminの２新薬開発 1980年代 1981 Colperminの英国発売 1986 Asacolの英国発売、→GSKに譲渡(英,Benelux,伊,スイス) 1986 Tillotts Pharma AGとしてスイス移転。 1990年代 1991 AsacolをP&Gに北米ライセンス、発売1992 1995 英Medeva plcに買収される。 Medeva plcは;Celltech plcに2000年に買収、Celltechが2004年UCB傘下となったため現UCB子会社]。 1999 経営陣が株式買収し、再び独立企業に戻る。 2000年代 2005 Tillotts' sales of Asacol have increased from 1996 to 2003 by a CAGR of 22.7%. Now available in 42 countries 2009.8 ゼリア新薬がTillotts Pharma AGを買収 - [日本語] [株主構成] 81% 従業員→といっても持ち株会ではなく経営者３人 19% UCB Pharma SA ← 旧Medeva plc ※株式非公開： 内容非公開 従業員数 99名/2004.2.2現在 Roland Bufton：28.5％(CEO and Chairman) Philip Parkes：19.0％(Non-Executive Directors on the Board) Susan Pearson：19.0％(Sales & Marketing Director)
●Tillotts Pharma AG[SZ] ●Our Products - Asacol[mesalamine;IBS炎症性腸疾患] - Colpermin[natural peppermint oil;IBS過敏性腸症候群] ●Press Releases - Development & Marketing of Asacol in Japan[2007.2.6] Asacolの共同開発・販売契約をゼリア新薬と協和発酵と締結。 ゼリアは潰瘍性大腸炎は単独で、クローン病は ゼ・協両社で開発。 日本のIBD患者数は10万人超。 IBDはクローン病と潰瘍性大腸炎の二つに分類。 AsacolはIBD世界市場シェア35%(IMS 2005/12) 本剤はTillottsにより1980年代半ば に開発され欧州で市販された。 Asacolの世界売上高はTillottsと他ルート合算で$600 million(2006)、世界５０ヵ国以上で販売。 - Tillotts Pharma licenses rights for Asacol in Japan[2004.2.2] ゼリア新薬に導出 - Tillotts Pharma AG licenses AsacolR in 11 countries to Lek Pharmaceuticals[2003.1.3]東欧 - ●Therapeutic Areas - IBD | IBS ●Product Development - Epanova[クローン病薬;EPA+DHA] | Xenema[難治性直腸・回腸嚢炎治療薬;] | Topasa[局所5-ASA]
■Titan Pharmaceuticals, Inc [米]
- http://www.titanpharm.com/index.php 1996.1 株式公開 2008.12 NYSE Euronext (formerly the American Stock Exchange)から撤退 ●会社決算●主要製品
($ 000) 2009/1-9 2008 2007 2006 2005 売上高 53 73 24 32 89 当期純利益 (4,104) (25,434) (17,647) (15,737) (22,462) 研究開発費 1,707 16,235 12,244 11,620 17,770 従業員数[連結] 4
●Iloperidone (FanaptmV) Schizophrenia, psychosis FDA承認；販売権Novartis kｿ 米加/Vanda - Rest of the world 【2009】Iloperidone (FanaptmV): An atypical antipsychotic approved by the U.S. Food and Drug Administration (“FDA”) for the treatment of schizophrenia. Novartis Pharma AG (“Novartis”) has acquired the U.S. and Canadian rights to further develop and commercialize the approved oral formulation, and also further develop and potentially commercialize a depot formulation. Vanda Pharmaceuticals, Inc. (“Vanda”) has the development and commercialization rights to the oral and depot formulations of this product for the rest of the world. We are entitled to a royalty of 8-10% on worldwide net sales for several years based on the remaining life of certain patents, and we anticipate commencement of royalty revenues from sales in the United States during the first half of 2010. Iloperidone (FanaptmV) was approved by the FDA in May 2009 for the treatment of schizophrenia and Novartis has acquired the rights to commercialize it in the U.S. and Canada. Novartis announced that it commenced commercial launch of Fanapt in January 2010.
Iloperidone (FanaptmV) is our novel, proprietary product approved in the U.S. on May 6, 2009 for the treatment of adult patients with schizophrenia. The Phase 3 clinical development was conducted initially by our sub-licensee, Novartis, and completed by Novartis’ sub-licensee, Vanda. In July 2008, Vanda received a non-approval letter from the FDA requesting additional information about the product. Vanda addressed the questions asked by the FDA and provided additional clarification following which the FDA granted marketing approval as noted above. The approval was supported by two placebo-controlled Phase 3 clinical studies comparing FanaptmV to placebo and active control in patients with schizophrenia, as well as safety data from more than 3,000 patients.
FanaptmV, a mixed dopamine D2 / serotonin 5HT2A receptor antagonist belonging to the class of atypical antipsychotics, will be commercialized in the U.S. and Canada by Novartis and the development of a depot formulation will also be pursued by Novartis.
Vanda has commercialization rights for the rest of the world for the oral formulation and the depot formulations, although Novartis has the first option to negotiate an agreement to co-market both these products in the rest of the world. Based on the terms of our sub-license agreement with Novartis we are entitled to royalty revenue of 8% of annual worldwide net sales up to $200 million and 10% of annual worldwide net sales above $200 million. We do not incur any expenses associated with this product.
【2009特許】We hold a license from Sanofi-Aventis under certain issued U.S. patents and certain foreign patents relating to iloperidone and its methods of use. Our license is exclusive for use in the treatment of psychiatric disorders, psychotic disorders and analgesia. The term of the U.S. patent that covers certain aspects of our iloperidone product expires in 2011, however it is anticipated that based on provisions of the Hatch-Waxman Act, the market exclusivity period for Fanapt will be extended by five years to 2016. The method of use patent covering the depot formulation will expire in 2020 assuming no further extensions. Prosecution of various divisional and continuation applications and their foreign counterparts continues satisfactorily, although it is uncertain whether additional patents will be granted.
●Probuphine: Opioid addiction P3；販売権Titan 【2009】An implant formulation of buprenorphine in Phase 3 clinical development for the treatment of opioid addiction that is capable of maintaining a stable blood level of the drug in patients for six months following a single treatment. We announced positive safety and efficacy results of this product in a placebo controlled Phase 3 study during 2008 and we have now completed approximately half of the overall clinical development program required for registration and potential approval of Probuphine. Recently we have been awarded a $7.6 million grant from the National Institutes of Health (“NIH”) that will partially fund the second Phase 3 controlled safety and efficacy study required by the FDA for product registration. Probuphine is currently in Phase 3 clinical development and although it has demonstrated efficacy in one controlled Phase 3 study, additional development is necessary prior to registration and it may still not be successfully developed or commercialized. Titan has been awarded a $7.6 million grant by the NIH in partial support of the second controlled Phase 3 study, however we will require significant further capital to support this and other clinical studies, manufacturing development, testing, and regulatory clearances prior to commercialization. We may experience unanticipated problems relating to product development and cannot predict whether we will successfully develop and commercialize any products.
● 【2009】
●Titan Pharmaceuticals, Inc [米] ●FINANCIAL FILINGS Form 10[2010.1.14] ●Products Iloperidone (FanaptmV) ●PRESS RELEASES Novartis Pharma Acquires Exclusive Rights From Vanda Pharmaceuticals for Commercialization of FANAPTmV[2009.10.12] Titan announces FDA approval of FANAPTmV[2009.5.7]
■Trimeris
- http://www.trimeris.com/ ; (Nasdaq: TRMS) 1999.7 RocheにFuzeon(T-20, enfuvirtide)の全世界開発販売権をライセンス。 Trimeris Announces 2008 Strategic Plan[2007.12.10] - Trimeris社は、従業員を減らし、次世代のHIV融合阻害剤TRI-1144のSAD(single ascending dose)第1相試験が2008年前半に完了したら研究開発機能を廃止すると発表したFuzeon はEU発売2003.6、米国発売2003.3 Fuzeonの出荷数量は、72,200キット(2007年), 79,700キット(2006年), 72,000キット(2005年)。(患者１人月１キット)
($ 000) 2007 2006 2005 2004 2003 2002 2001 備考 Milestone 9,435 3,430 1,722 2,152 2,964 1,133 1,304 Fuzeon分Rocheから Royalty 15,727 11,812 8,784 4,556 755 - - Fuzeon分Rocheから米加外分 Collaboration 24,223 21,738 8,553 (16,125) (25,515) - - Fuzeon分Rocheから米加分 (総収入) 49,385 36,980 19,059 (9,417) (21,796) 1,133 1,304 研究開発費 12,883 18,333 18,274 21,313 36,823 51,226 58,440 一般管理費 11,100 12,453 9,436 10,151 8,577 10,985 9,953 (原価経費 計) 23,983 30,786 27,710 31,464 45,400 78,933 72,218 営業利益 25,402 6,194 (8,651) (40,881) (67,196) (77,800) (70,914) 経常利益 27,801 7,407 (8,106) (40,088) (65,703) (75,678) () 当期純利益 27,425 7,384 (8,106) (40,088) (65,703) (75,678) (66,741) 従業員数[連結] 9(技術1) 64(技術39) 90(技術56) 97(技術60) 100(技術70) Fuzeon売上(Roche) 266,796 248,951 208,211 135,216 36,555 [enfuvirtide]融合阻害薬 うち米加(調整前) 147,454 152,166 132,609 99,908 32,245 Roche うち米加(調整後) 124,3(-7.3) 134,161 112,734 85,693 28,345 Roche うち米加以外 142,450(+24.1) 114,790 95,477 49,523 8,210 Roche ●競合(2007)
We are engaged in a segment of the biopharmaceutical industry, the treatment of HIV, that is intensely competitive and changes rapidly. FUZEON competes, and our developmental stage HIV fusion inhibitor, TRI-1144, will compete, with numerous existing therapies. For example, there are 29 different drugs that are currently approved in the United States for the treatment of HIV. In addition, a number of companies are pursuing the development of novel pharmaceutical products that target HIV. Some companies, including several multi-national pharmaceutical companies, are simultaneously marketing several different drugs and may therefore be able to market their own combination drug therapies. We believe that a significant number of drugs are currently under development and will become available in the future for the treatment of HIV.
FUZEON is delivered via twice daily subcutaneous injections, each delivering 90 mg of FUZEON. The other approved anti-HIV drugs are delivered orally at various dosing intervals. We believe that this delivery method is one factor that may limit its uptake as compared to other competing drugs. In addition, the WAC of FUZEON is approximately $25,700 for one year of therapy. This price is significantly higher than any of the other approved anti-HIV drugs. FUZEON's price relative to other approved anti-HIV drugs may also limit patient demand.
The standard of care for the treatment of HIV is to administer a regimen that combines drugs from each of the different classes of anti-HIV drugs. In the event drug candidates are approved that are effective against an HIV virus that has become resistant to currently approved drugs, we believe that using these drugs in combination with FUZEON may provide patients with additional treatment options that do not currently exist. These drugs may be either competitive with FUZEON, or synergistic with FUZEON, or in some circumstances, both.
The need for drugs that have a novel mechanism of action has stimulated interest in the inhibition of HIV entry into the cell. Several companies are developing or attempting to develop HIV drug candidates that inhibit entry of the virus by targeting one of the HIV co-receptors (i.e. either CCR5 or CXCR4). In 2007, Pfizer Inc. received U.S. marketing approval from the FDA for a CCR5 inhibitor, Maraviroc. Also in 2007, Schering-Plough Corp announced the initiation of Phase III studies for its CCR5 inhibitor, Vicriviroc. CCR5 inhibitors impede entry of the virus into the cell through a mechanism that is different from FUZEON.
In the latter part of 2007, Merck & Co., Inc. received U.S. FDA marketing approval for their integrase inhibitor, Raltegravir. Integrase inhibitors represent a novel class of antiretroviral drug and, like FUZEON, may be well-suited to therapy for treatment-experienced patients. Gilead Sciences, Inc. is also developing an integrase inhibitor (Elvitegravir) which is currently in clinical testing. Other companies, including Panacos Pharmaceuticals, Inc., are developing new classes of drugs with novel targets (e.g. Panacos' maturation inhibitor, Beviramat). Tibotec Therapeutics has developed a next generation non-nucleoside reverse transcriptase inhibitor (“NNRTI”) with activity against viruses that are resistant to earlier forms of NNRTIs. Tibotec's drug, Etravirine, received U.S. FDA marketing approval in early 2008.
We anticipate that we will face intense and increasing competition in the future as these and other new products enter the market and advanced technologies become available. Existing products or new products for the treatment of HIV developed by our competitors may be more effective, less expensive, or gain wider acceptance by patients and physicians than FUZEON or any other products eventually commercialized by us.
Many of our competitors have significantly greater financial, technical and human resources than we have and may be better able to develop, manufacture, sell, market and distribute products. Many of these competitors have products that have been approved or are in late-stage development. These competitors also operate large, well-funded research and development programs. In addition, smaller companies may prove to be significant competitors, particularly through collaborative arrangements with large pharmaceutical and biotechnology companies. Furthermore, academic institutions, governmental agencies and other public and private research organizations are becoming increasingly aware of the commercial value of their inventions for the treatment of HIV and are more actively seeking to commercialize the technology they have developed.
New developments in our areas of research and development are expected to continue at a rapid pace in both industry and academia. Our drug candidate TRI-1144, if successfully developed and approved, would face competition based on:
・ the safety and effectiveness of the products; ・ the convenience of the dosing regimen; ・ the timing and scope of regulatory approvals; ・ availability of manufacturing, sales, marketing and distribution capabilities; ・ reimbursement coverage; ・ price; and ・ patent position.While our experience to date is that new, active HIV drugs and those in clinical development have been used synergistically with FUZEON in order to achieve maximal viral suppression in treatment experienced patients, we cannot guarantee that this will translate into increased patient adoption. Our competitors may develop more effective or more affordable technology or products, or achieve earlier patent protection, product development or product commercialization than we can. Our competitors may succeed in commercializing products more rapidly or effectively than we can, which could have a material adverse effect on our business, financial condition, results of operations and the market price of our stock.★新規参入
In 2007, two new antiretroviral agents received U.S. FDA marketing approval (SELZENTRY(R) and ISENTRESS(R)) with a third (INTELENCE(R)) approved in January 2008. Data from clinical trials with these new agents continued to demonstrate the benefits of combining FUZEON in regimens that contain these new, active agents. Nevertheless, the availability of a variety of new active agents for use in treatment-experienced patients has placed significant pressure on U.S. FUZEON. Sales for the fourth quarter of 2007, in dollars, were down 25% as compared to the fourth quarter of 2006. Each of these new agents are administered orally and have the potential to provide experienced patients with a more convenient treatment regimen.
★Alternative Administration
Since the commercial launch of FUZEON in 2003, we, along with Roche, have been exploring ways to enhance a patient's ability to initiate and remain on FUZEON containing therapies, including the potential for using the Biojector 2000 (“B2000”) needle-free delivery system.
The B2000 has been used to deliver millions of injections in a wide range of healthcare settings since receiving FDA approval in 1996. The B2000 needle-free injection works by forcing medication rapidly through a tiny orifice held against the skin, creating a fine stream of fluid that penetrates the skin and deposits medication in the subcutaneous tissue. Positive data from the T-20 405 bioequivalence study of the B2000 needle-free device (versus standard needle/syringe) formed the basis for a supplemental NDA application (“sNDA”) to the FDA in May 2005 to include use of the B2000 for administration in the FUZEON label.
In 2005, the FDA issued an approvable letter regarding the B2000 sNDA. In its reply, the FDA indicated that the filing was approvable pending receipt of the final study report from the ongoing FUZEON WAND (With a Needle-Free Device; ENF-404) study, a randomized, open-label, two-way, cross-over study assessing the tolerability of the B2000 device for administration of FUZEON.
In 2006, the Company presented results from the WAND trial, showing that it achieved the primary endpoint of a 50% reduction in the incidence of painful injection site reactions or ISR's with use of the B2000 needle-free device compared to standard needle-syringes (36% for the device vs. 71% for needle-syringe, p<0.01). Following use of both administration systems, 84% of patients preferred the B2000 needle-free device versus 16% favoring standard needle/syringe administration.
Later that same year, the Company and Roche had discussions with the FDA regarding the submission of an amended sNDA for inclusion of the B2000 device as an administration option for FUZEON. The FDA acknowledged that, based on currently available evidence, administration with B2000 achieves similar blood levels of FUZEON compared to standard needle-syringe administration. However, the FDA indicated that a small number of certain adverse events related to administration of FUZEON with the B2000 device (hematomas and nerve pain) warrant review of additional information in order to better characterize the incidence of these events. Some of these events were associated with use of B2000 to deliver FUZEON either in close proximity to bone joints or into scar tissue. In the current product label, FUZEON is recommended for injection in the upper arm, upper leg and stomach. The FUZEON labeling also cautions against injecting into scar tissue.
Based on this information, the FDA requested additional safety information on the nature and occurrence of ISRs, including data from the FUZEON BOSS (Biojector Open Label Safety Study; ENF 407) trial, as well as from other data sources. Initiated in 2006, BOSS has completed enrollment of approximately 330 current or prior FUZEON patients at 43 trial sites in the U.S. and Puerto Rico in an eight-week study to assess the safety and patient acceptance of B2000 compared to standard needle-syringe administration for FUZEON. Data from BOSS were reported at ICAAC in September 2007 and indicated that use of the B2000 device was associated with an improved ISR profile in ENF-experienced patients, including a reduction in the incidence and severity of treatment-limiting ISRs, and was preferred by the patients compared to a needle and syringe (87.2% vs. 12.5%, respectively).
In advance of receiving additional B2000 safety data, the FDA requested and received changes to the current FUZEON labeling (both Package Insert and Patient Injection Instructions) to add precautions regarding hematoma and nerve pain associated with B2000 administration, as well as precautions regarding the use of the B2000 device in patients with bleeding disorders. In October of 2007, Roche and Trimeris announced that they were withdrawing the sNDA for the B2000 based on a comprehensive assessment of the clinical program as well as the significant delay in achieving U.S. regulatory approval due to the time required to generate additional data. Patients currently administering FUZEON with the device were not advised to discontinue use of the B2000 for administration as long as they continued to follow the precautions in the FUZEON label.
★Current and Future FUZEON Clinical Trials
Following the Company's reduction-in-workforce in 2006 and 2007, Roche has taken the primary role in conducting our current and future FUZEON clinical trials. Roche will be responsible for conducting ongoing clinical trials with FUZEON during 2008. The table below summarizes recently completed, clinical trials.
The T20 BOSS trial involves the use of the currently approved Biojector 2000 needle-free injection device manufactured by Bioject Medical Technologies, Inc., described above.
Name Description T20 BOSS An assessment of the use of the B2000 system in patients at risk of discontinuing FUZEON therapy due to injection-related difficulties. T20 Intense Comparative trial in earlier line patients assessing ongoing FUZEON use compared to an induction/ maintenance approach. T20 SwitchTox An assessment of the substitution of Anti-Retrovirals (“ARV's”) associated with undesirable side-effects/toxicities in favor of FUZEON. T20 BLQ An assessment of FUZEON in combination with an investigational protease inhibitor.
There are no further clinical trials with FUZEON planned for initiation in 2008.
●Trimeris ●Fuzeon ●Pipeline ■Investors ●Annual Reports 2006 Annual Report[2008.1.30] ●SEC Filings 10-K Annual Filings[2008.3.17] - [pdf] - [word] - [xls] ●Press Release Trimeris Reports Financial Results for the Fourth Quarter and Year End 2007[2008.3.13] - Trimeris Reports 2007 FUZEON(R) Sales Results[2008.1.29] - Trimeris Announces 2008 Strategic Plan[2007.12.10] - Trimeris社は、従業員を減らし、次世代のHIV融合阻害剤TRI-1144のSAD(single ascending dose)第1相試験が2008年前半に完了したら研究開発機能を廃止すると発表した Roche and Trimeris Provide Update on Development of Alternative Administration Options for Delivery of FUZEON(R)[2007.10.3] - 無針注射器Biojector(R) 2000 申請取り下げ。 Fuzeonは注射部位反応(ISR)が98%に発生し問題視されていた。 New Interim Results Demonstrate High Response Rate With FUZEON(R) Plus Darunavir Regardless of Existing Protease Inhibitor Resistance[2007.7.20] - New Trial to Study Investigational Integrase Inhibitor in Combination with FUZEON(R) Once-Daily Dosing Strategy[2007.7.17] - Trimeris Announces Management Changes[2007.3.15] - CEO & CFO退任。 Trimeris and Roche Amend Research Agreement Covering Next-Generation HIV Fusion Inhibitors[2007.3.15] - 次世代融合阻害剤TRI-1144の全権をRocheがTrimerisに返還。 Updated HIV/AIDS Treatment Guidelines Support Use of FUZEON Plus an Active Boosted Protease Inhibitor to Achieve New Treatment Goal[2005.10.13] - U.S. FDA Grants Traditional Approval for FUZEON(R), First and Only Fusion Inhibitor for the Treatment of HIV[2004.10.15] - FUZEON(R) to be Widely Available Through Specialty and Retail Pharmacies in the U.S.[2004.4.14] - Roche and Trimeris Submit 48-Week Data to U.S. FDA for Full Approval of FUZEON(R), First and Only HIV Fusion Inhibitor[2003.12.16] - New Data Confirm Durable Benefit of FUZEON-Based Regimens Among Treatment-Experienced HIV Patients, Including Those With Less Advanced and Late Stage Disease[2003.10.27] - Trimeris Announces Status of FUZEON Sales and Launch Plans[2003.9.25] - New Data Show FUZEON-Based Regimens Continue to Provide Significant Durable Response in Treatment-Experienced HIV Patients Through 48 Weeks[2003.9.15] - New Data Show FUZEON-Based Regimens Deliver Superior, Sustained Response In Treatment-Experienced Patients[2003.7.15] - The New England Journal of Medicine Publishes Results of Pivotal Trials Demonstrating Efficacy and Safety of FUZEON(TM), World's First FDA-Approved HIV Fusion Inhibitor[2003.5.28] - European Commission Approves FUZEON(TM), First HIV Fusion Inhibitor, for Use Against HIV in the European Union[2003.5.27] - Final Topline Results Show Significant Durable Response at 48 Weeks in HIV Patients Treated with FUZEON(TM) in Combination Therapy[2003.4.28] - Preliminary 48-Week Results Show Longer Term Response in HIV Patients Treated With FUZEON(TM) (enfuvirtide), First Fusion Inhibitor[2003.3.20] - U.S. FDA Approves FUZEON(TM); First Drug to Block Entry of HIV into Immune Cells[2003.3.13] - [] -
■Tyco International Ltd
- http://www.tyco.com/wps/wcm/connect/tyco+home/Home ●決算(連結) ９月度決算 ($ Million) 2003.9 2002.9 2001.9 2000.9 1999.9
総収入 $36,801.3 $35,589.8 $34,002.1 $28,927.5 $22,494.1
製品売上 $29,427.7 $28,741.8 $28,953.1 サービス 7,373.6 6,848.0 5,049.0
営業利益 1,034.7 (2,838.2 ) 3,894.9 4,318.5 873.7 純利益 979.6 (9,179.5 ) 3,464.0 4,318.5 873.7 従業員数 258,600 米国 102,900 米国外 155,700 ●セグメント別(連結) ９月度決算 ($ Million) 2003.9 2002.9 2001.9 2000.9 1999.9
総収入 $36,801.3 $35,589.8 $34,002.1 $28,927.5 $22,494.1
火事・Security$11,292.8 $10,639.0 $ 7,473.0 製品 $ 5,124.1 $ 4,955.5 $ 3,494.4 サービス 6,168.7 5,683.5 3,978.6 電子機器 $10,355.0 $10,464.1 $13,545.6 製品 $ 9,900.3 $10,015.5 $13,115.7 サービス 454.7 448.6 429.9 技術製品 $ 4,684.4 $ 4,709.3 $ 4,170.8 製品 $ 4,010.1 $ 4,064.1 $ 3,594.5 サービス 674.3 645.2 576.3 ヘルスケア $ 8,571.9 $ 7,899.1 $ 7,065.3 製品 $ 8,496.0 $ 7,828.4 $ 7,001.1 サービス 75.9 70.7 64.2 プラスチック $ 1,897.2 $ 1,878.3 $ 1,747.4 Adhesives 製品 $ 1,897.2 $ 1,878.3 $ 1,747.4 サービス - - -
●製品群別売上高(連結) ９月度決算 ($ Million) 2003.9 2002.9 2001.9
総収入 $36,801.3 $35,589.8 $34,002.1
Electronic Security Services $6,361.6 $5,991.9 $3,696.4 Fire Protection Contracting and Services 4,931.2 4,647.1 3,776.6 Electronic Components 8,093.0 7,581.1 8,919.5 Wireless 771.5 811.7 673.1 Electrical Contracting Services 369.6 346.3 335.7 Power Systems 567.7 623.0 918.3 Printed Circuit Group 402.8 416.2 863.0 Submarine Telecommunications (1) 150.4 685.8 1,836.0 Medical Devices & Supplies 6,694.9 6,252.8 5,983.2 Retail 903.8 762.9 318.3 Pharmaceuticals 973.2 883.4 763.8 Flow Control and Fire Products 2,717.1 2,789.0 2,252.9 Electrical and Metal Products 1,349.5 1,434.4 1,397.9 Infrastructure Services 617.8 485.9 520.0 Plastics 999.8 950.4 835.5 A&E Products 296.2 321.6 343.3 Adhesives 343.3 348.0 331.9 Ludlow Coated Products 257.9 258.3 226.8 ADT Automotive - - 9.9
Net revenues from external customers $36,801.3 $35,589.8 $34,002.1 ●地域別(連結) ９月度決算 ($ Million) 2003.9 2002.9 2001.9
総収入 $36,801.3 $35,589.8 $34,002.1
米国 $19,838.7 $20,308.2 $19,728.0 他のアメリカ 1,844.3 2,007.2 2,176.6 欧州 9,719.0 8,358.2 7,591.0 アジア太平洋 5,399.3 4,916.2 4,506. LIST OF MAJOR TYCO ACQUISITIONS FY2001 MALLINCKRODT
●Tyco International Ltd ●Our Businesses ★Tyco Healthcare →Covidien plc[アイルランド] [2007.06.07]Tyco InternationalからCovidien and Tyco Electronics1をスピンオフ ★Security solution ★Fire Protection ★Flow control ●Newsroom ■Investor Relations ★Financial Reports 2010 Annual Report ★SEC Filings 10-K Annual Report[2011.11.16] - [pdf] ★Press releases
■UCB
- 2004.7 UCB SAは英Celltech Group plcを買収(100%)。 関連記事|関連記事2 2006.9.25 UCBは、独Schwarz Pharmaとの事業統合契約調印。 その後UCBがSCHWARZ PHARMA株総数の87.6%を取得。 UCB子会社 2007.12末(UCB名以外) Schwarz Pharma AG[GE],Melusin Schwarz GmbH[GE],Schwarz Biosciences GmbH[GE],Schwarz & Co[GE] 旧セルテック系 Celltech Group Ltd[英],Celltech Pharma Beteiligungs GmbH[GE],Chiroscience Group Ltd[英] Cistron Biotechnology Inc[米],Confirmant Ltd.[英] Darwin Discovery Ltd[英],Evans Healthcare Ltd.[英],International Medication Systems (UK) Ltd. Oxford GlycoSciences[英],Oxford GlycoTherapeutics Ltd[英],Upstate Pharma LLC[米] Medeva Holdings B.V.[蘭],Medeva Pharma Suisse SA[瑞] その他 M.I.O. Zwijnaarde N.V.[BE], Sifar S.A.[BE] Vedim Pharma S.N.C.[FR] Vedim Pharma GmbH[GE],Rodleben Pharma GmbH[GE],Celltech Pharma GmbH & Co Kg[GE] Sanol GmbH[GE],Hoyer GmbH & Co[GE],Paul Hoyer GmbH[GE] Intermuti Pharma GmbH[GE],Bredus Pharma GmbH AG[GE] Fipar Ltd.[英],Viking Trading Co Ltd[英],Vedim Ltd[英],Medo Pharmaceuticals Ltd[英] Kremers Urban Development Company[米],SRZ Properties Inc.[米],CPM Properties Inc.[米], Kremers Urban LLC[米] Ilika Epikalipseon Hellas EPE[GREECE],Ilika Epikalipseon Hellas EPE[INDIA],Kudco Ireland Ltd[IRELAND] Instituto de Farmacoligia Espanol S.L[Spain],Doutors Reassurance SA[瑞] Cogefina SA[瑞],Fipar (Thailand) Ltd[タイ],Mesulin Ilac ve Maddeleri Pazarlama TLS[トルコ] ●会社決算* 2005.1.1 会計処理基準をGAAP→IFRS 5に変更。旧2004=GAAP ●事業別売上
(Euro milllion) 2008 2007 2006 2005 2004 2003 2002 2001 2000 純売上高[継続事業] 3,027(-5) 3,188 2,177
旧2,188(+7)2,043(+22) 1,674 Royalty収入[継続事業] 396(+35) 294 335 298(+41) 211 その他収入[継続事業] 178(+24) 144 39 総収入[継続事業] 3,601(-1) 3,626 2,551
旧2,523(+8)2,341(+24) 1,885 純売上高[中止事業] 191 1,382 Royalty収入[中止事業] - 1 総収入[中止事業] 191 1,383 純売上高 計 2,234 3,056 Royalty収入 計 298 212 総収入 計 2,532 3,268
旧3,068(+3)2,966(+18) 2,514 2,475 2,204 売上原価[継続事業] 1,047 541 550 424 売上原価[中止事業] 売上原価 計 粗利益[継続事業] 2,455(-5) 2,579 2,010
旧1,9821,791 1,461 営業利益[継続事業] 480 475 364 281 営業利益[中止事業] 16 105 営業利益 計/EBIT 113(-67) 344 571 364
旧380386 営業利益EBITA 507(+4) 487 503 466 377 経常利益[継続事業] 367 270 280 経常利益[中止事業] 14 78 経常利益 (-43) 219 517 362 484 483 494 462 370 当期純利益[継続事業] (12) 159 367
旧392275
旧270(+37)197 当期純利益[中止事業] 55 2 - 485 132 当期純利益 42 160 367(-51) 755(+130) 329
旧363(+7)340 332 318 269 研究開発費[継続事業] 767 788 615 511 361 研究開発費[中止事業] - - - 5 34 研究開発費 615(+20) 516 395 270 262 218 182 従業員数 11,292 12,102 8,477 8,525 11,403
医薬8,59811,559 10,326 10,013 9,910 * "Surface Products"事業は、まずSpecialty Filmsを2004.9.30にInnovia plcに売却(Euro 320m)。 次にSpecialty Chemicalsを2005.2.28にCytec Industries Incに売却(Euro 1,415m)。 ●医薬セクター：地域別
(Euro milllion) 2008 2007 2006 2005 2004 2003 2002 2001 2000 純売上 2,234 3,056
旧3,068(+3)2,966(+18) 2,514 2,475 2,204 医薬セクター 2,043 1,674
旧1,679(+15)1,463(-1) 1,476 1,427 1,149(+27) Surface製品 191 1,382
旧1,387(-8)1,501(+45) 1,037 1,048 1,055 その他 - - 3 2 1 ●製品売上
(Euro milllion) 2008 2007 2006 2005 2004 2003 2002 2001 2000 欧州 1,414(+5) 1,351 1,311
旧826786[38%] 40% 40% 40% 41% 45% アメリカ 1,193(-17) 1,452 1,425
旧1,003895[44%] 40% 40% 39% 35% 28% アジア・太平洋 - - - - - 19% 19% 23% 25% 日本 195 230[11%] 12% その他 404(+5) 385 409
旧164132[7%] 9% 1% 2% 1% 2% 医薬 計 3,027 3,188 3,144
旧2,188(+7)2,043[100%] 100 100 100 100 100 * 2004年 Pro Formaベース(Celltech売上高含む) **Zyrtec 2005年Zyrtec-D/Cirrusを含む。 ●メモ ●Vimpat(lacosamide) 抗てんかん剤 [2008] The rejection of lacosamide in diabetic neuropathic pain (DNP) by the U.S. Food and Drug Administration (FDA) was a disappointment. While Phase III clinical trials have demonstrated clinical effect, the magnitude of effect in this indication has not convinced the regulatory authorities. We are reviewing what additional steps may be needed to make lacosamide available for patients with DNP in the U.S. and Europe. Vimpat(R) in epilepsy and diabetic neuropathic pain In September 2008, Vimpat(R) was approved in Europe as adjunctive therapy for the treatment of partial-onset seizures in adults with epilepsy. By year-end, the drug was launched in Germany and in the U.K. Epilepsy specialists have responded positively to the launch of Vimpat(R) and over 4 500 patients have already been prescribed the drug as an add-on to their current medication. In October 2008, Vimpat(R) was approved in the U.S. as adjunctive therapy for partial-onset seizures in adults with epilepsy. Vimpat(R) will be launched in this market in early 2009 by the established UCB epilepsy team. In July 2008, UCB received an Action (‘Not Approvable’) Letter from the FDA for lacosamide in the treatment of diabetic neuropathic pain (DNP) in adults. In September 2008, UCB withdrew the European Marketing Authorisation Application for lacosamide in DNP. UCB has taken this decision based on the view of the CHMP that the magnitude of the clinical effect of lacosamide in DNP has not been convincingly established. UCB is considering whether to initiate additional clinical trials to answer this concern. ・ Vimpat(R) approval in Europe in epilepsy: The European Commission approved in September 2008 Vimpat(R) (lacosamide) as adjunctive therapy in the treatment of partial-onset seizures with or without secondary generalisation in patients with epilepsy aged 16 years and older. Launched within days in Germany and the U.K.
(Euro milllion) 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 備考 ★中枢神経系 [47%] [37%] 763 586(+18) Keppra 1,266 1,026(+35) 761(+36) 560(+34) 417(+33) 314(+36) 231(+89) 122(+) 31 [levetiracetam]抗てんかん 米 768 645(+34) 482(+35) 356(+32) 270(+29) 209(+53) 164 96 29 米発売2000.4;米シェア21%(2003.11);初AED；てんかん 欧 437 340(+88) 251(+34) 187(+37) 137(+38) 100(+52) 66 26 2 SZ 2000.4 他 60 41(+14) 27(+67) 16(+67) 10 5 1 - - Keppra XR 10 - [levetiracetam]抗てんかん;米発売2008.10 Nootropil 93 101(+2) 99(-4) 103(+0) 103(-11) 115 129 136(+) 130 [piracetam]皮質性ミオクローヌスに対する抗てんかん剤などとの併用療法 欧 69(-8) 75 [] 他 24(-8) 26 [] Atarax - 55 54(+11) 49(+9) 45(+4) 43 41 41(+14) 36 [hydroxyzine]ataraxics 抗不安 Metadate CD/
Equasym XL77 81 68(+35) 51 11
*46- - - - - [Methylphenidate-SR]ADHD治療薬;2009.2→Shireに譲渡 米Matadate CD 60(-8) 66 [] Neupro 58 52 10 - [rotigotine transdermal system]パーキンソン病 米 5(-51) 10 [] 欧 53(+26) 42 [] Vimpat 2 - - - [lacosamide]てんかん薬 他のCNS 10 - - - - ★アレルギー [14%] [21%] 704(+2) 688(+6) 649
旧731(+9)- - - - - Xyzal 173 168(+18) 143(+13) 126(+21) 104(+157) - - - - - [levocetirizine]アレルギー、持続性製剤;EU発売2001 米 3 2 欧 143 143(+20) 124(+9) 113(+18) 96 他 26 22(+3) 19(+44) 13(+49) 9 Zyrtec 249 487(-13) **561(+0) **562 494(-15) 581(-3) 670 724 756 641(+18) [cetirizine]Allergy 米 9(-96) 237(-37) 273(+12) 244(+4) 236(-10) 262 欧 87(-3) 89(-10) 100(-9) 110(-23) 142
旧238(+5)227 日 110 116(-7) 138(-17) 166(+39) 119(-6) 127 - - - - 国内シェア15.5%(2003) 他 43 45 50(+20) 42(-10) 47
旧5654 Pfizer royalty 30 149 135 132 145 151 Zyrtec-D/Cirrus - - - - 50(+8) 46 - - - - [cetirizine+pseudoephedrine]鼻閉薬 Tussionex 147 114(+9) 105(-3) 108(+32) 63(-)
*82- - - - - [hydrocodone]鎮咳剤。米国のみで販売 Atmadisc 48 47 [fluticasone/salmeterol]喘息 他のアレルギー 30(-) - - - - - ★その他 Cimzia 10 1 - - [certolizumab pegol]クローン病 米 8 0 - [] Omeprazole米国 75 147(-24) 192 [omeprazole]潰瘍;米国 PEPTIDES - - 2(-95) 46(+17) 39 39 49 39 41 Lortab - - 20(+0) 20(-3) 20 28 42 45(+) 39 analgesic[hydrocodone-paracetamol] BUP4 - - 20(-28) 28(-3) 29 28 28 28 17 [propiverine]尿失禁・頻尿治療剤バップフォー うち日本 20(-28) 28(-3) 29 Frova - - - - - 21 7 - - - [frovatriptan succinate]片頭痛 STOGAR - - - - - 15 17 16 7 - [ラフチジン]ストガー錠：H2拮抗剤 うち日本 14(-10) 15(+0) 15 SOMATOSTATIN - - - - - 15 14 14 13 Duratuss - - - - - ? ? 24(+) 14 Anti-cough[hydrocodone-pseudoephedrine+guaifenesin] Delsym/米 - - 22(-31) 31 14
*29(dextromethorphan polistirex)鎮咳剤 その他 878(-13) 1,012 332(-7) 358 284
*388
旧362(+22)175 194 230 194 うち日本 23(+12) 21 29 合計 3,027(-5) 3,188(+1) 3,144 2,043(+11) 1674(+15)
*1,8471463 1476 1427 1149 うち日本 195(-15) 230(+20) 192 []
・ Vimpat(R) U.S. approval in epilepsy: At the end of October 2008, the FDA approved Vimpat(R) for use as an add-on therapy for the treatment of partial-onset seizures in people with epilepsy who are 17 years and older. Vimpat(R) will be launched in the U.S. in early 2009, expecting scheduling.
・ Vimpat(R) U.S. not-approvable letter in diabetic neuropathic pain: At the end of July 2008, UCB received a notapprovable letter from the FDA for Vimpat(R) in diabetic neuropathic pain.
・ Vimpat(R) file withdrawn in Europe in diabetic neuropathic pain: In September 2008, UCB withdrew the Marketing Authorisation Application with the European Medicines Agency (EMEA) for Vimpat(R) in the treatment of diabetic neuropathic pain, in view of the magnitude of the clinical effect not having been convincingly established.
UCB is considering initiating an additional clinical programme to further substantiate the magnitude of effect of lacosamide in diabetic neuropathic pain.
・ Lacosamide Phase IIa programme in fibromyalgia: Following Phase IIa results announced in June 2008, a decision whether to start a Phase IIb with lacosamide to treat fibromyalgia will be made in 2009.
・ Lacosamide results in migraine prophylaxis: In February 2009, UCB announced top-line results for a proof-ofconcept Phase IIa clinical trial to assess the efficacy and safety of lacosamide in migraine prophylaxis. While the study did not achieve statistical significance for the primary endpoint, UCB will evaluate development plans once full analyses are available.
・ New products Cimzia(R) (certolizumab pegol) and Vimpat(R) (lacosamide) were launched in 2008 (in April in the U.S. for Cimzia(R) and in September in Germany and the U.K. for Vimpat(R)) with net sales of respectively Eur 10 million and Eur 2 million.
・Neupro [2008] While these challenges were expected, a deviation from the product specifi cation of NeuproR triggered an unexpected setback in the year. Our decision to recall the product created an outof- stock situation in the U.S. and limited availability in Europe. In Europe, a cold chain storage and distribution system has enabled us to continue to supply NeuproR to patients. In 2009, all patients, including new patients, should be able to benefi t from this innovative therapy for Parkinson’s disease and restless legs syndrome. In the U.S. we have begun a dialogue with the regulatory authorities to bring NeuproR back to American patients. NeuproR in restless legs syndrome - In April 2008, the CHMP issued a positive opinion recommending that the EMEA grants a marketing authorisation for NeuproR in the symptomatic treatment of moderate-tosevere idiopathic restless legs syndrome (RLS) in adults, in Europe. UCB plans to launch the RLS indication in Europe during the first half of 2009, pending European authority approval of the cold chain storage and distribution solution to the product specification deviation issue. In the U.S. the supplemental New Drug Application (sNDA) for the use of NeuproR as a treatment for moderate-to-severe RLS was accepted for filing by the FDA in December 2007. In December 2008, UCB received a Complete Response Letter from the FDA in which the FDA noted the substantial evidence of effectiveness of NeuproR in both advanced Parkinson’s disease and RLS. Before approving the drug for these indications however, the FDA has requested to see resolution of the product specification deviation which had caused UCB to withdraw the product from the U.S. market in March 2008. UCB intends to continue its dialogue with the FDA about the re-launch of NeuproR in the U.S. ・Keppra [2008] In 2008, UCB had to absorb the effect of the ZyrtecR patent expiry in the U.S. in December 2007, as well as the loss of exclusivity of KeppraR in the U.S. where we have faced new generic competition since November 2008. In June 2008, the FDA granted paediatric exclusivity for KeppraR in the U.S. This extended the period of exclusivity on KeppraR across all licensed indications by six months to January 2009. Following a settlement between UCB and Mylan, Mylan launched its generic version of KeppraR 250 mg, 500 mg and 750 mg tablets in the U.S. in early November 2008. Also in June 2008, UCB and Otsuka Pharmaceuticals announced a co-promotion agreement in Japan for KeppraR for the adjunctive treatment of partial-onset seizures. UCB has submitted a fi le for the approval of KeppraR in epilepsy to the Japanese authorities in November 2008. KeppraR XR, an extended release formulation of levetiracetam, was launched in October 2008 in the U.S. generating sales of . 10 million by the end of the year. [2006] Keppra(R): Net sales of Keppra(R) (levetiracetam) rose by 201 million euro or 36% (+37% at constant exchange rates) from 560 million euro in 2005 to 761 million euro, thanks to its golden standard status and the new regulatory filings which have enhanced the momentum (intravenous launch in the U.S.A. And Europe, 1 gram launch, Juvenile Myoclonic approval, monotherapy approval for Europe, Korea and China approvals). Solid performance was experienced in all regions: U.S.A. (+37% at constant exchange rates to 482 million euro), Europe (+34% at constant exchange rates to 251 million euro) and Emerging Markets (+68% at constant exchange rates to 27 million euro). Keppra(R) reinforced its U.S. Leadership position in value in the new anti-epileptic market. In Europe, Keppra(R) became market leader. [2005] 2005年度抗てんかん剤市場で、米国リーダーシップ地位獲得、欧州は獲得近づく。 ・Cimzia(R)(certolizumab pegol). /Crohn's disease and rheumatoid arthritis [2008] CimziaR in Crohn's disease was approved and successfully launched in Switzerland in January 2008 and in the U.S. in April 2008, generating total sales of Euro 10 million. Since its launch, over 3 500 patients have been prescribed the product and more than 5 000 gastroenterologists have enrolled in the UCB CIMplicity. programme which helps patients with nursing and reimbursement support. In Europe, EMEA’s Committee for Medicinal Products for Human Use (CHMP) rejected the appeal by UCB against the CHMP's refusal of marketing authorisation for CimziaR in the treatment of patients with Crohn’s disease in March 2008. In June 2008, UCB and Otsuka Pharmaceuticals announced a co-promotion agreement in Japan for CimziaR for the treatment of Crohn’s disease. The companies plan to submit the filing dossier for CimziaR in Crohn’s disease to the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) in 2009. In February 2008, the FDA agreed to accept, for fi ling and review, a Biologics License Application for CimziaR for the treatment of adult patients with active rheumatoid arthritis. In July 2008, the European Marketing Authorisation Application for CimziaR for the treatment of rheumatoid arthritis was accepted for review by the EMEA. The review of CimziaR by the EMEA for the treatment of rheumatoid arthritis is ongoing. In January 2009, UCB received a Complete Response Letter from the FDA asking the company to submit an additional safety data update. In early February 2009, the company met with the FDA in order to understand the authority’s requirements. UCB intends to provide the FDA with the data it requires by the end of the fi rst half of 2009. If approved, CimziaR will be the fi rst and only PEGylated anti-TNF (Tumour Necrosis Factor) biologic therapy available for the treatment of this disease. ・Zyrtec [cetirizine] [2006] Zyrtec(R): Net sales of Zyrtec(R) (cetirizine), including the decongestant form (Cirrus(R) or Zyrtec-D(R)), decreased by 1 million euro or 0% variance from 562 million euro to 561 million euro, reflecting sustained growth in the U.S.A. And Emerging Markets, compensating for the particularly weak pollen season in Japan as well as the further erosion in Europe due to generic competition, reimbursement reforms and the conversion to Xyzal(R). Zyrtec(R) net sales reported by UCB for the U.S.A. Reflect UCB's portion of the gross profit realised by Pfizer and UCB as well as the sales of bulk cetirizine to Pfizer or 273 million euro in total for 2006. The total U.S. Net sales of Zyrtec(R) and Zyrtec-D(R) increased by 15% from 1 362 million U.S. dollar to 1 568 million U.S. dollar. Zyrtec(R) has strengthened its U.S. Market leadership reaching a market share of 34.0% at the end of December 2006 (based on the number of treatment days). The 10% growth of Xyzal(R) from 113 million to 124 million euro slightly more than compensated for the decrease in Zyrtec(R) and Cirrus(R) net sales from 110 million euro to 100 million euro. In Japan, the entire antihistamine market decreased in 2006 with a below-average pollen season following an exceptionally severe pollen season in 2005. The combined Zyrtec(R) market share achieved by our co-distributors, Dai-Ichi and GSK Japan, reached 10.1% by the end of 2006 (on the basis of the number of treatment days) slightly below that of the market leader. This resulted in a decrease of 17% (or .12% at constant exchange rate) in Zyrtec(R) net sales in Japan from 166 million euro to 138 million euro. [2005] ・2005年欧州では対ジェネリック競争激化、Xyzalにシフト。 ・日本では2005.7.1からGSKと共同販売 ・Xyzal [levocetirizine] [2006] Xyzal(R): Net sales of Xyzal(R) (levocetirizine) continued their steady growth in the antihistamine market from 126 million euro in 2005 to 143 million euro in 2006, or 13% increase both at real and constant exchange rates. The growth in Europe of 9% (or +10% at constant exchange rates) to 124 million euro off-sets the decline in Zyrtec(R) net sales. Xyzal(R) is now market leader in 11 European countries with, as of the end of 2006, a combined share of the European antihistamine market in the main 5 European countries of 13.4% (based on the number of treatment days). Penetration in Emerging Markets improved with Xyzal(R) net sales increasing by 44% to 19 million euro. [2005] 2005年抗ヒスタミン剤市場で欧州７カ国で市場リーダーで主要５ヵ国でシェア12% ・アレルギー・フランチャイズ(Zyrtec, Xyzal) [2006] Allergy franchise: Given the extended growth of Xyzal(R), the sustained Zyrtec(R) performance in the U.S.A. And Emerging Markets, and despite a decline in Japan and further losses of Zyrtec(R) in Europe, net sales for the total Allergy franchise increased by 2% (or +4% at constant exchange rates) year-over-year from 688 million euro to 704 million euro. On the basis of the number of treatment days, the market share of UCB's allergy franchise at the end of 2006 amounted to 34.0% in the U.S.A., 18.9% in Europe and 10.1% in Japan. [2005] 2005年市場シェアは米32.2%欧18.5%日9.8%。 ●UCB's new development pipeline /2007.11.12●開発段階
★CNS Indications 段階 Vimpat®(lacosamide) epilepsy adjunctive therapy (EU) 申請 [備考] Vimpat®(lacosamide) diabetic neuropathic pain (EU) 申請2007.8.17 [備考] Neupro® Patch(Rotigotine Transdermal System) advanced Parkinson's disease (US) Phase 3 Vimpat®(lacosamide) diabetic neuropathic pain (US) Phase 3 Vimpat®(lacosamide) epilepsy adjunctive therapy (US) Phase 3 Vimpat®(lacosamide) epilepsy monotherapy (US) Phase 3 Keppra® XR(levetiracetam) epilepsy (US) Phase 3 Rikelta(TM)(brivaracetam)(UCB 34714) epilepsy Phase 3 Rikelta(TM)(brivaracetam)(UCB 34714) Unverricht Lundborg Disease (ULD) Phase 3 Xyrem®(sodium oxybate) fibromyalgia Phase 3 rotigotine patch restless legs syndrome Phase 3 Lacosamide fibromyalgia Phase 2 Lacosamide migraine prophylaxis Phase 2 Lacosamide osteoarthritic pain Phase 2 rotigotine patch fibromyalgia Phase 2 rotigotine nasal spray restless legs syndrome Phase 2 CDP323 multiple sclerosis Phase 2 [備考]Biogen Idecと共同開発[2006.10.2];経口 ★Inflammation Indications 段階 Cimzia®(certolizumab pegol)(CDP870) Crohn's disease (EU+US) FDA申請2006.2.28
EU申請2006.4.28[備考][2007.6.1]PRECiSE 3（P3）は、CIMZIA(TM)の第III相試験PRECiSEプログラムの継続試験として行われた長期オープンラベル試験です。DDWで発表した試験結果には、CIMZIA(TM)の効果が18ヶ月間持続した患者の中間解析も一部含まれています。これらの患者は、PRECiSE 1（P1）またはPRECiSE 2（P2）を終了した後、52週目にP3に登録されました。4週ごとにCIMZIA(TM)（400mg）を継続的に皮下投与した結果、80週目には85％以上の患者において臨床効果の維持が認められ、約74％で緩解が得られました。 Cimzia®(certolizumab pegol)(CDP870) rheumatoid arthritis Phase 3 [備考][2007.7.5]2007年6月14日（中央ヨーロッパ標準時午前7時）、スペインのバルセロナにて開催された年次欧州リウマチ学会で新しく報告された主要試験（RAPID 1及びRAPID 2）の結果によると、世界初のFcを持たないPEG化抗TNF製剤、CIMZIA(TM)（一般名：セルトリズマブ ペゴル）とメトトレキサート(以下、MTXと略す)の併用療法が、MTX単剤療法に比べ、活動性関節リウマチの徴候及び症状を迅速かつ有意に軽減することがわかりました。
従来のRAの治療法には、非ステロイド系抗炎症剤（NSAIDs）、コルチコステロイド類、疾患修飾性抗リウマチ薬（DMARDs）などがあり、最近は生物学的製剤による治療法が選択肢に加わりました。抗TNF（TNF-α；腫瘍壊死因子）製剤は、RA患者用の薬剤として承認されている特別なモノクローナル抗体（生物学的製剤）です。単独で投与する場合もありますが、通常はMTXか他の免疫抑制剤との併用で投与します。関節破壊の進行予防の可能性を有する抗TNF製剤の有効性は立証されており、関節破壊に直接あるいは間接的に関与する炎症性メディエータ、TNF-αの作用を抑制することが分かっています。
CIMZIA(TM) （セルトリズマブ ペゴル）は国内外の臨床試験で使用されている治験薬剤です。CIMZIA(TM) は、世界初のFc部分を持たないPEG化抗TNF（腫瘍壊死因子）抗体で、RAを対象に、2週および4週毎の皮下投与について評価が行われています。CIMZIA(TM) は、従来の抗TNF製剤のようにFc部分を介して惹起される細胞毒性を発現することなく効果を発揮することが示されています。
CIMZIA(TM) はヒトTNF-αに対して高い親和性を示し、TNF-αの病態生理学的作用を選択的に中和します。過去10年間で、TNF-αは基礎研究および臨床研究の主要なターゲットとして脚光を浴びています。このサイトカインは病的な炎症を介在する上において重要な役割を果たし、過剰なTNF-α産生は様々な疾患において直接的に関与しています。Cimzia®(certolizumab pegol)(CDP870) psoriasis Phase 2 [備考] epratuzumab systemic lupus erythematosus
(※Immunomedics, Incから全世界権利)Phase 2 [備考] anti-Sclerostin(CDP7851) bone loss disorders Phase 1 [備考] ★Oncology Indications 段階 CDP791 non-small-cell lung cancer Phase 2 [備考]ImClone Systems Incorporatedから全世界権利取得[2005.8.16]；a novel, investigational antibody targeting the vascular endothelial growth factor receptor-2 (VEGFR-2). EGFR-2 is known to regulate the formation of blood vessels in tumours (angiogenesis), allowing cancer cells to receive nutrients and maintain growth. CDP-791 takes the novel approach of targeting and blocking VEGFR-2 on blood vessel cells with a PEGylated diFab antibody and thus interferes with the development of tumour vasculature. CMC544 non-Hodgkin's lymphoma Phase 1 ★Other Indications 段階 fesoterodine overactive bladder 申請 ●リスト除外 Xyrem(sodium oxybate) Nalcolepsy随伴cataplexy EU承認2007.3.12
独発売2005.12.8
EU承認2005.10.13
EU承認勧告2005.6.29
EU申請(2004)
CelltechEquasym XL
(methylphenidate)ADHD 2005.2英国発売
EU相互承認2006.5.24Neupro® Patch(Rotigotine Transdermal System) Early-Stage Parkinson's disease (US) 米発売2007.7.16
FDA承認2007.5.9Xyzal(levocetirizine) １日１回and outdoor allergies, as well as chronic idiopathic urticaria(US) 発売2007.10.2
FDA承認2007.5.29[備考]XYZALは米国では、2007.5承認、2006.9にsanofi-aventisと共販開始。現在80ヵ国で販売。 [米適応]for the relief of symptoms associated with allergic rhinitis (seasonal and perennial) and the treatment of uncomplicated skin manifestations of chronic idiopathic urticaria in adults and children 6 years of age and older. Kentera(TM)(oxybutynine) 過活動膀胱[EU] EU発売2005.4.18 [備考]経皮パッチ;Watson Pharmaceuticals incから欧州Lic;米国では2003.2承認、OXYTROL(R)として販売 Keppra(levetiracetam) てんかん：Tonic-clonic seizures FDA承認2007.3.20
EU承認2007.1.16
日本P3Keppra(levetiracetam) てんかん：単独療法 EU承認2006.8.18 Keppra(levetiracetam) てんかん：Myoclonic seizures EU承認2006.5.15 Keppra(levetiracetam) 注射剤(静注) FDA承認2006.8.2
米国申請2004.12
EU承認2006.3
EU申請2005.3[備考]初の緊急静注AED; FDA適応「for use as adjunctive therapy in the treatment of partial-onset seizures in adults with epilepsy」 Keppra(levetiracetam) 小児てんかん：４才～16才 FDA承認2005.6.24
EU承認2005.9.22[備考]Keppraは1999年に米国で「成人の部分てんかんの追加療法」で承認。欧州では同じ適応症で2000年に承認。 現適応「add-on therapy in the treatment of partial-onset seizures in children four years of age and older with epilepsy.」 [備考]
薬剤 適応 段階 備考 Keppra てんかん 日本P3 brivaracetam
(UCB34714)てんかん, pain, tremor P2 seletracetam
(UCB44212)てんかん, pain P2 Keppra 経口液 米国発売
EU申請Keppra 社会不安障害[SAD] P3 中止? Keppra 帯状疱疹後神経痛 P3 Keppra レボドパ誘発Diskynesia P2 中止? Keppra １日１回錠剤 中止? Keppra 速効溶解錠剤 中止? Nootropil mild cognitive impairment P4 Xyzal(levocetirizine) 抗炎症特性 P4 Xyzal(levocetirizine) 競合格差 P4 Xyzal(levocetirizine) 経口液 EU申請 Xyzal(levocetirizine) Persistent鼻炎 EU申請 Xyzal(levocetirizine) アレルギー性喘息 P3計画 Xyzal(levocetirizine) 小児喘息予防(EPAAC) P3 Zyrtec Chewable錠 米国承認 efletirizine アレルギー性鼻炎,urticaria, bid P2完了 efletirizine １日１回錠 前臨床 UCB35440 アレルギー性喘息 P2 延期 Dynavax Allergy,免疫調整 P2 中止? ★アレルギー Xyzal(levocetirizine) 独～承認(2000)、発売(2001早々) efletirizine (ucb28754) は臨床試験の最終段階が2003年開始
抗アレルギー剤 Zyrtec(cetirizine)
Xyzal(levocetirizine)Seasonal Allergic Rhinitis(SAR)
Perennial Allergic Rhinitis(PAR)
Chronic idiopathic Urticaria(CIU)Zyrtec-D/Cirrus
(cetirizine+pseudoephedrine)Seasonal Allergic Rhinitis(SAR)
Perennial Allergic Rhinitis(PAR)抗てんかん剤 Keppra(levetiracetam) 成人部分onset seizuresへのAdd-on治療 Nootropics Nootropil(piracetam) Cognitive enhancer(主にElderly)
Cortical myoclonus
Sickle form anaemia消化器 Somatostatin-UCB(somatostatin) 急性胃腸出血
腸管・膵臓fistulae
●UCB ●News ●Products ●Patients ●R&D ★R & D Pipeline ■Investors Relations ●News - UCB to divest Equasym(R)[2009.2.20] - UCB has agreed the sale of Equasym(R) IR and Equasym(R) XL (methylphenidate HCl) for the treatment of attention deficit hyperactivity disorder (ADHD) to Shire. With the exception of the U.S., Canada and Barbados, world-wide product rights and relevant staff for Equasym(R) IR/XL are being acquired by Shire. UCB will receive an up-front payment totalling EUR 55 million and additional undisclosed milestone payments if Shire meets certain pre-defined sales targets. Equasym(R) IR/XL sales in 2008 were approximately EUR 17 million. - UCB: Full Year 2008 Financial Results[2009.3.3] - UCB: Full Year 2007 Financial Results[2008.2.29] - UCB Full-Year 2006 Financial Results[2007.2.28] - UCB Group confirms its previously announced 2004 results and provides IFRS reconciliation and product update[2005.3.23] - UCB Group preliminary full-year 2004 results[2005.2.7] ●INVESTORS ★Annual Reports - Annual Report 2008[pdf,146p] - Annual Report 2007[pdf,146p] - Annual Report 2006[pdf,128p] - Annual Report 2005[pdf,140p] - Annual Report 2004[pdf,76p] - Annual Report 2003[pdf,72p] - Annual Report 2002 ★Schwartz Pharma ★Celltech ●Presentations～半期報告など UCB GROUP Company Presentation[2008.4.7;pdf,35p] Analyst Meeting Presentation Half-Year Results 2007[2007.7.26;pdf,85p] UCB GROUP Company Presentation September 2007[2007.9.20;pdf,43p]
●UCB Pharma - http://www.ucbpharma.com/ ●Media Centre - Press Releases CORPORATE PRESS RELEASES [INVESTOR RELATIONS]～通常型プレスリリース MEDICAL PRESS RELEASES～製品毎 UCBは医薬事業のみになったので、UCBと同一。 ●About UCB ●Products ●Therapeutic Areas～疾病専門サイト http://www.theucbinstituteofallergy.com/ －アレルギー http://www.ucbepilepsy.com/ －てんかん http://www.ucb-bioproducts.com/ －蛋白 http://www.memorycare.net/ －呆け ●R & D
●ユーシービージャパン - http://www.ucbjapan.com/home - 2000年六月に富士レビオから医薬品事業部門を譲受し、自販体制 ●ニュース - [] ●疾病情報 ●医療用医薬品情報 ●鼻アレルギー情報センター - http://www.nasal-allergy.net/ ★医薬事業譲受から１年「自販品も拡大基調」ユーシービージャパン [薬事日報01.9.5] ＵＣＢ・Ｊの二〇〇〇年度売上高は二五五億円にも達し、このうち最主力品のアレルギー 性疾患治療剤「ジルテック」（販売：住友製薬、第一製薬）は二〇〇億円を超えた。今年 に入ってからも好調で、同疾患領域のNo.２の座に成長した。 旧富士レビオ製品のうち、昨年四月に発売されたH2受容体拮抗剤「ストガー」、持続性 Ca拮抗降圧剤「シナロング」、尿失禁・頻尿治療剤「バップフォー」を自販の三本柱に据えている。
■Celltech Group
1980 創立 英国初のバイオテク企業として 1990 分社化 Celltech Therapeutics and Celltech Biologicsに。 株式上場 ※Medirace and Evans Medical が合併し、英国ワクチン企業Medeva PLCに。 1993 ※Medevaは仏Institute Recherche Corbiereを買収しEvans Medical SAに改名 1994 ※MedevaはEvans Medical, Medevale Pharmaservices, IMS (UK)の国際事業を統括 1996 Celltech BiologicsをAlusuisse-Lonzaに売却。 1997/8 ※Chiroscienceは子会社ChiroTech and Rapigene を設立 1999 Chiroscience plc[設立1992]と合併しCelltech Chiroscience(現Celltech R&D)を設立 2000 Celltech Chiroscienceは Medeva plc.を買収し、Celltech Group plc.となる。 Celltechは非中核事業(Evans Medical含む)を切り離しPowderject and the Armstrong Inhalon businessesに. 2001 CelltechはCistron Biotechnology Inc.を買収。同社はリウマチ等炎症疾患を適応 とするinterleukin-1-beta標的抗体を開発 グループ再編。Celltech R&D (旧Celltech Chiroscience)、Celltech Pharmaceuti cals (旧 Celltech Medeva). Celltech Group plc はドイツThiemann Arzneimittel GmbHを買収。 2004 UCBの傘下にはいる。 UCB S.A. launches a friendly offer to acquire Celltech Group plc, the leading UK-based biotech company[2004.5.18] UCB has over 90% of Celltech Shares[2004.7.9] 子会社(Celltech名以外の) /2003.12末 Chiroscience Group Limited Chiroscience R&D Limited. Cistron Biotechnology, Inc. Confirmant Limited Evans Healthcare Limited Darwin Discovery Limited. Darwin Molecular Corporation IMS (Overseas) S.A. International Medication Systems (UK) Limited Medeva Limited Medeva International Limited Medeva Holdings B.V. Medeva France S.A.Medeva B.V Medeva Pharma Schweiz AG Medevale Pharmaservices Limited. Oxford GlycoSciences Limited Oxford GlycoSciences (UK) Limited Oxford GlycoTherapeutics Limited Oxford GlycoSciences Inc Upstate Pharma, LLC ●製品売上高*At constant 2003 exchange rates. ●決算
(￡ milllion) 2003 2002 2001 2000 1999 備考 主力製品 Tussionex (US) 68.1(+4) 65.6 (hydrocodone polistirex & chlorpheniramine polistirex) 鎮咳剤 Metadate CD (US) 20.2(+22) 16.6 **20.4 **26.3 **39.4 (methylphenidate HCl徐放)ADHD;**Methylphenidate製剤計 Delsym (US) 18.0(+37) 13.1 (dextromethorphan polistirex)鎮咳剤 Dipentum (US/Europe) 17.1(+289) 4.4 (olsalazine sodium)潰瘍性大腸炎 Perenterol (Germany) 7.8(0) 7.8 (saccaromyces)整腸、乾癬 Coracten (UK) 7.1(+13) 6.3 (nifedipine)血圧降下剤 Total key promoted brands 138.3(+22) 113.8 他の主要製品 Zaroxolyn (US) 25.3(-3) 26.2 (Metolazone)利尿剤 Generic methylphenidate(US/欧) 9.8(-16) 11.7 (methylphenidate HCl)ADHD Ionamin (US) 5.0(-2) 5.1 (phentermine resin)食欲減退剤 Semprex-D (US) 4.0(+67) 2.4 (acrivastine & pseudoephedrine HCI)アレルギー性鼻炎 Pediapred (US) 1.4(-61) 3.6 (prednisolone sodium phosphate)経口 Other products (US/Europe) 75.4(-7) 81.4 Total other products 120.9(-7) 130.4 Total product sales 259.2(+6) 244.2 Effect of exchange differences - 8.7 As reported 259.2(+2) 252.9 ●収入内訳
(￡ milllion) 2003 2002 2001 2000 1999 備考 売上高 353.3(+7) 329.6 営業利益 251.8(+7) 234.9 経常利益 47.0(+15) 40.9 純利益 44.4(+4) 42.8 研究開発費 106.1(+11) 95.7 * At constant 2003 exchange rates. ★ADHD [2003] In anticipation of the launch of Metadate(R) CD in mid-2001, the US sales force was expanded in order to maximize the market opportunity offered by this product. Following an appraisal of in-market performance of Metadate(R) CD, we significantly reduced the level of detailing for this product, which resulted in the US general sales force being reduced from 350 to 170 representatives during the third quarter of 2002. The restructured sales force will continue to detail our cough/cold range of products (including Tussionex(R) and Codeprex(R) which we intend to launch in the third quarter of 2004), and will support Metadate(R) CD, which is promoted predominantly to pediatricians and child psychiatrists. Since the sales force restructuring, Metadate(R) CD has made a positive financial contribution to the business. In addition, the US gastrointestinal sales force established in January 2003 which consists of 30 representatives will continue to promote Dipentum(R) and establish important relationships in advance of commercialization of CDP 870.
(￡ milllion) 2003 2002 2001 2000 1999 備考 製品売上高 259.2(+6) 244.2 ロイヤリティ収入 Antibody engineering 62.7(+28) 48.8 Pertactin 8.6(-15) 10.1 (acellular pertussis vaccine) Asacol 6.1(-13) 7.0 (mesalazine)潰瘍性大腸炎、クローン病 Mylotarg 3.1(+24) 2.5 (gemtuzumab ozogamicin)白血病Wyeth Other 3.1(+48) 2.1 83.6(+19) 70.5 Exchange gains on forward contracts 10.5 - Total royalties 94.1(+33) 70.5 Total sales 353.3(+12) 314.7 Effect of exchange differences - 14.9 As reported 353.3(+7) 329.6 Equasym XL(R) We submitted an application for a marketing authorization in the UK for Equasym XL(R), a once daily ADHD product, in July, 2003. We expect to launch the product in the UK during 2004. Following approval in the UK, we anticipate seeking additional approvals in other key European territories for a 2005 launch.
Metadate(R) CD. Following approval by the US FDA in April 2001, we launched this new biphasic once-daily controlled release formulation of methylphenidate. Metadate(R) CD is indicated for the treatment of attention deficit hyperactivity disorder, or ADHD. This controlled release product avoids the need for a midday dose, thus improving convenience and addressing potential concerns with pediatric patients relating to the administration of this treatment during the school day. In 2001 we increased our US sales force for the launch and initial marketing of Metadate(R) CD. Following an appraisal of in-market performance of Metadate(R) CD, however, we significantly reduced the level of detailing for this product, which resulted in the US general sales force being reduced from 350 to 170 representatives during the third quarter of 2002. The restructured sales force supports a more focused marketing campaign for Metadate(R) CD. In 2003, the product was re-packaged (100 count bottles) and two new dosage strengths were added (10 & 30 mg capsules, in addition to the original 20 mg capsules). Since that time, prescriptions have consistently grown. The product is promoted predominantly to pediatricians and child psychiatrists by our primary care sales force. Notwithstanding the increasingly competitive nature of the ADHD market, Metadate(R) CD is expected to continue to make a positive financial contribution to the business in 2004, particularly following the restructured sales force and introduction of the 10 mg and 30 mg dosage strengths. In the UK, this product will be marketed under the trademark Equasym(R) XL. During 2003, Equasym(R) XL was filed for approval in the UK and is expected to be launched in European territories towards the end of 2004/beginning of 2005, with the European organization able to build on experience from this product in the US.
In March 2002 a comparative clinical trial of Metadate(R) CD Extended-Release Capsules and McNeil's (a Johnson & Johnson Group company) Concerta(R) Extended-Release Tablets, the current market leader in the once-daily methylphenidate market segment, was initiated. The study, published in the March 2004 on-line issue of “Pediatrics,” showed that once-daily Metadate(R) CD Extended-Release Capsules were more effective than Concerta(R) in children with ADHD during the morning hours, and that the two treatments were similar in efficacy during the afternoon. The study also showed that, with near-equal daily doses, the overall behavioral effects of Metadate(R) CD were greater than those for Concerta(R) across time periods corresponding to a typical school day (averaged over 1.5-7.5 hours post dose).
Methylphenidate. Methylphenidate is used in the treatment of ADHD in children and young adults. The DEA classifies methylphenidate as a Schedule II controlled substance.
In addition to 10 mg, 20 mg and 30 mg Metadate(R) CD, our methylphenidate range in the US consists of 5 mg, 10 mg and 20 mg immediate release tablets, and 10 mg and 20 mg extended release tablets. All the immediate release formulations and the 10 mg and 20 mg extended release tablets are generic equivalents of formulations of the branded product Ritalin which is sold in the US by Novartis AG. The 10 mg and 20 mg extended release tablets are marketed in the US under the trademark Metadate(R) ER. In May 2000, we obtained a license in Europe for the immediate release methylphenidate range and launched the product in the UK under the trademark Equasym(R).
[2002]
Our attention deficit/hyperactivity disorder franchise achieved modest growth. Our franchise consists of branded Metadate(R) CD and the generic methylphenidate range. Together the franchise achieved sales of ￡30.5 million compared with the ￡29.0 million achieved during 2001. During 2002, Metadate(R) CD continued to maintain a share of approximately 9% of the once daily methylphenidate market and achieved sales for the year of ￡18.0 million (2001: ￡8.6 million). During 2002 we announced positive results from a head-to-head study against the then and still market leader in the once daily methylphenidate segment. The study was designed to confirm that the pharmacokinetic profile of Metadate(R) CD translates into improved clinical control during the school day. The positive results from this study were in a peer review journal during 2003.
●Celltech Group - http://www.celltechgroup.com/ ■Celltech Group SEC Filings Form 20-K[2004.6.25] 6-K[03/16/2004] -2003決算 Annual Report 2003[pdf,88p]
■United Therapeutics Corporation
--- http://www.unither.com/； 従業員数410人 NASDAQ "UTHR." 本社1110 Spring Street, Silver Spring, Maryland 20910. 1966.6 米国DelawareにLung Rx, Inc.として設立 1997.12 United Therapeutics Corporationに社名変更 ★系列会社 Unither Pharmaceuticals, Inc. (UPI) 100%子会社 Lung Rx, Inc. 100%子会社 Northern Therapeutics, Inc.,カナダ (2000)Lung Rx, Inc.により設立 ●決算●売上
($ 000) 2009 2008 2007 2006 2005 2004 2003 2002 2001 備考 総収入 369,848 281,497 210,943 159,632 115,915 73,590(+38) 53,341(+77) 30,120 5,731 営業経費 研究開発費 122,188 239,181 83,352 57,570 36,052 30,602 35,417 26,778 32,590 販売管理費 176,338 94,306 99,027 54,028 24,655 21,529 22,667 15,889 16,943 販売原価 45,321 30,066 22,261 17,028 12,315 8,250 6,783 5,456 3,137 計 343,847 363,553 204,640 130,650 73,022 60,381 64,867 48,123 52,670 営業利益 26,001 (82,056) 6,303 28,982 42,893 13,209 (-11,526) (-18,003) (-46,939) 純利益 19,462 (49,327) 12,353 73,965 65,016 15,449 (-9,969) (-23,651) (-37,288) 従業員数 410 360 320 285 210 170 160 ●United Therapeutics' Products United Therapeutics' product portfolio includes the following: * Including Germany, but excluding the rest of Europe and the Middle East.
($ 000) 2009 2008 2007 2006 2005 2004 2003 2002 2001 備考 総収入 369,848(+22.9) 281,497(+33.5) 210,943(+32.1) 159,632(+37.7) 115,915 73,590(+38) 53,341(+77) 30,120 5,731 ●製品売上 357,870 270,005 201,348 - 110,412 69,539 49,715 26,677 2,565 (Remodulin) 331,579(+22.9) 269,718(+34.3) 200.879(+31.7) 152,478(+39.6) 109,200 66,050 45,121 21,200 493 [treprostinil](2002.5発売)肺高血圧 (Tyvasco) 20.268 - []肺高血圧 (Adcirca) 5.789 - [tadalafil]肺高血圧 ●サービス売上 10,751 9,258 7,435 - 0
旧5,2414,051 3,626 3,443 2,529 Telemedicine services and products 10,968(+15.6) 9,485(+22.8) 7,725(+17.1) 6,597(+14.3) 5,773 5,346 ●他の製品 60(-66.5) 179(-67.9) 557(-19.2) 689 2,194 ●ライセンス収入(2008迄旧Distributor fees) 1,227 2,234 2,160 - ライセンス収入 1,244(-45.8) 2,294 - 262 - - - - From SEC Filings - 10-K[2010.2.26,pdf] [6p]
Product Mode of Delivery Indication/Market Current Status UT Territory Remodulin Continuous subcutaneous Pulmonary arterial hypertension [発売済]U.S.,EU大半,Australia,Canada,Israel , Mexico, Argentina and Peru Worldwide Remodulin Continuous intravenous Pulmonary arterial hypertension 発売済U.S.,Canada, Israel, Mexico, Argentina and Peru Worldwide Tyvaso(treprostinil sodium) Inhaled Pulmonary arterial hypertension 発売済U.S. Worldwide Adcirca (tadalafil) Tablets Oral Pulmonary hypertension Commercial in the U.S. and Puerto Rico United States/Puerto Rico CardioPAL® SAVI and Decipher
Cardiac MonitorsTelemedicine Cardiac arrhythmias and ischemic heart
diseaseCommercial in the U.S. Worldwide CardioPAL SAVI Wireless
Cardiac Event MonitorsTelemedicine Cardiac arrhythmias and ischemic heart
diseaseCommercial in the U.S. Worldwide Oral Treprostinil Oral Pulmonary arterial hypertension Phase III Worldwide Beraprost-MR Oral Pulmonary arterial hypertension Phase II North America/Europe 3F8 MAb Intravenous Neuroblastoma Phase II Worldwide Oral Treprostinil Oral Peripheral vascular disease Phase II Worldwide Aviptadil Inhaled Pulmonary hypertension and other
pulmonary diseasesPhase II Worldwide 8H9 MAb Intravenous Metastatic brain cancer Phase I Worldwide IW001 Oral Idiopathic Pulmonary Fibrosis and
Primary Graft DysfunctionPhase I Worldwide Glycobiology Antiviral Agents Oral Hepatitis C and other infectious diseases Pre-Clinical Worldwide
●United Therapeutics Corporation ●Products http://www.remodulin.com/ ■Investor Relations ●Annual Reports ●SEC Filings - 10-K annual report [2010.2.26;] - 10-K annual report [2009.2.26;] - 10-K annual report [2008.2.29;] - 10-K[2007.2.28] - 10-K[2006.2.27,pdf,108p] - 10-K[2005.3.3,pdf,85p] - 10-K[2004.3.12,pdf,71p] ●Press Release United Therapeutics Reports 2003 Annual Financial Results[2004.2.24]
■Valeant Pharmaceuticals International
http://www.valeant.com/; (NYSE: VRX); Based in Aliso Viejo, California 1960 ICN Pharmaceuticals, Inc. is founded as International Chemical and Nuclear Corporation 1970s ICNはL-dopaのFDA初承認、売上高は$100 million超、NY市場に上々、主力は自社開発のribavirin 1980s ICNは拡大しICN Pharmaceuticalsが親会社。 ICN Biomedicalsは世界最大のバイオ企業。 SPI Pharmaceuticalsは600製品以上を製造販売。 Viratek, Incが研究開発企業。 1990s 上記企業群が統合し、ICN Pharmaceuticals, Inc. となる。 2003 ICNは社名変更し、Valeant Pharmaceuticals International (NYSE:VRX),に。 ●経営実績●製品売上高 see 117p
($000) 2007 2006 2005 2004 2003 2002 2001 (製品売上高) 785,770 781,562 731,869
旧732,240609,212
旧607,824518,598 466,513 485,018 (ロイヤルティ) 86,452 81,242 91,646 76,427 167,482 270,265 136,989 売上高 872,222 862,804 823,515 685,639
旧684,251685,959
旧686,080736,778 622,007 営業利益 75,315 7,974 (50,251)
旧(96,824)5,517
旧4,34821,471 (42,908) 192,091 経常利益(継続) 26,054 (56,817) (139,126)
旧(130,339)(120,362)
旧(52,236)(66,690)
旧(13,862)164,794 116,067 当期純利益 (6,186) (57,568) (188,692)
旧(118,143)(154,653) (57,527) (144,524) 63,295 研究開発費 98,025 105,442 114,100 92,858 45,344 50,567 29,014 取得研究開発費 - - 126,399
旧173,59911,770 117,609 - - 従業員数[連結] 3,001 (a) 2003は薬効別集計がされず、数値が得られない。 ★Infergen C型肝炎 2005.12.30 InterMune社から米・加の販売権買収。(1.2億ドルcash). We paid InterMune milestoneとして2007.1 ($2,585,000)、2007.7(500万ドル)支払った。 2007.9 Infergen売却を決定し、 2008.1.14 Three Rivers Pharmaceuticals, LLCに売却した。
($000) 2007 2006 2005 2004 2003 備考 ●神経系薬剤 Mestinon 53,012(+11) 47,625(+9) 43,531 41,631 41,879 [pyridostigmine bromide]重症筋無力症 Diastat AcuDial 51,264(+1) 50,678(+6) 43,535
旧47,631- - [diazepam rectal gel] Cesamet 30,173(+59) 18,985(+90) 10,029 4,957 3,258 [nabilone]嘔吐抑制剤 Librax 17,170(+16) 14,835(-18) 18,159 16,868 11,774 []沈静・鎮痙剤 Migranal 13,354(+17) 11,592(-10) 12,949 - - []片頭痛 Dalmane/Dalmadorm 11,432(+4) 10,957(-11) 12,285 12,146 10,636 [Flurazepam]催眠鎮静剤 Tasmar 10,262(+57) 6,534(+12) 5,829 3,551 - [tolcapone]パーキンソン病薬 Melleril 8,206(+28) 6,431(+110) 3,068 [thioridazine]統合失調症 Zelapar 5,747(+44) 3,981(-) - []パーキンソン病薬 Limbitrol - - 5,858 5,869 5,244 [] その他 66,677(+6) 63,033(+10) 54,658 40,624 (a) 小計 267,477(+14) 234,651(+11) 210,888
旧210,909125,646 (a) ●感染症薬剤 Virazole 14,350(-13) 16,552(+0) 16,547
旧16,55715,553 18,843 [] Infergen 42,716 - - - - [interferon alfacon-1]C型肝炎 その他 19,813(-2) 20,144(-6) 21,459
旧21,46544,607 (a) 小計 34,163(-7) 36,696(-3) 38,006
旧38,02260,160 (a) ●皮膚疾患薬剤 Efudix 71,714(-8) 78,336(+30) 60,179 45,453 26,821 []日光角化症・基底癌 Kinerase 30,126(+4) 28,929(+30) 22,267 15,619 12,628 [N6-furfuryladenine]皺取り Oxsoralen-Ultra 12,377(+18) 10,527(+12) 9,365 10,910 8,501 [] Dermatix 14,043(+39) 10,139(+10) 9,189 7,034 2,493 [] Eldoquin 6,316 6,099 3,875 [] その他 39,059(-7) 42,023(+10) 34,366 45,685 (a) 小計 167,319(-2) 169,954(+22) 139,246
旧141,682130,800 (a) ●他の領域薬剤 Bedoyecta 42,384(-15) 49,935(+7) 46,762 30,654 26,955 [VB1,6,12混合] Solcoseryl 23,749(+26) 18,916(+0) 18,983 14,3697 16,186 [] Bisocard 22,559(+42) 15,927(+24) 12,847 10,613 7,075 []高血圧・狭心症 M.V.I.(multi-vitamin infusion) 11,708(-12) 13,350(+76) 7,602 7,123 [] Nyal 11,060(+8) 10,216(-26) 13,747 11,904 8,969 []OTC消炎鎮痛 Espaven 8,458(-24) 11,147(+20) 9,258 7,010 6,512 [] Protamin 6,924(+8) 6,384(+6) 6,047 []ヘパリン中和剤 Calcitonin - - 9,645 10,420 13,638 [] Aclotin - - 5,643 5,606 5,852 [] Espacil - 5,565(-7) 5,979(+19) 5,028 4,938 [] その他 189,969(-11) 214,386(-6) 218,627 195,586 282,521 [] 小計 316,811(-7) 340,261(-1) 343,729 291,218 372,646 製品売上高 合計 785,770(+1) 781,562(+7) 731,869 607,824 518,598 []
●Valeant Pharmaceuticals International ●Products ★Dermatology Dermatix() 瘢痕再建ジェル Efudex/Efudix(5-FU) Kinerase() Oxsoralen-Ultra() ★Infectious Disease Infergen(Interferon alfacon-1) Ｃ型肝炎 Virazole(ribavirin for inhalation) RSV下気道感染 ★Neurology Mestinon(pyridostigmine bromide) 重症筋無力症(Myasthenia gravis:MG) Tasmar(tolcapone) パーキンソン病薬 Zelapar(selegiline HCl) パーキンソン病薬 ●Media Center ★News Releases ★Financial Reports ★Annual Reports ★ ●Investor Relations ★News Releases ★Financial Reports ★Annual Reports ★SEC Filings 10-K[2008.3.17] - [pdf,217p] 10-K/A[2007.1.23] - [pdf,142p] 10-K[2006.3.16] - [pdf]
■Vanda Pharmaceuticals,Inc[米]
- http://www.vandapharma.com/ ●会社決算●主要製品
($) 2009 2008 2007 2006 2005 売上高 4,547,744 - - - - 営業利益 (35,947,943) (52,845,121) (80,038,375) (65,708,440) (24,286,653) 経常利益 (35,858,846) (51,064,241) (74,059,811) (63,510,619) (23,876,652) 当期純利益 (35,858,846) (51,064,241) (74,069,690) (63,511,168) (23,884,301) 研究開発費 13,873,961 23,935,541 47,234,867 52,070,776 16,890,615 従業員数[連結] 20
●Iloperidone (FanaptmV) Schizophrenia, psychosis FDA承認；販売権Novartis kｿ 米加/Vanda - Rest of the world 【2009】Fanapt(tm)(iloperidone), a compound for the treatment of schizophrenia. On October 12, 2009, we entered into an amended and restated sublicense agreement with Novartis. We had originally entered into a sublicense agreement with Novartis on June 4, 2004 pursuant to which we obtained certain worldwide exclusive licenses from Novartis relating to Fanapt(tm)
. Pursuant to the amended and restated sublicense agreement, Novartis has exclusive commercialization rights to all formulations of Fanapt(tm) in the U.S. and Canada. On January 11, 2010, Novartis launched Fanapt(tm) in the U.S. Except for two post.approval studies started by us prior to the execution date of the amended and restated sublicense agreement, both of which were substantially completed by December 31, 2009, Novartis is responsible for the further clinical development activities in the U.S. and Canada, including the development of a long.acting injectable (or depot) formulation of Fanapt(tm)
. Pursuant to the amended and restated sublicense agreement, we received an upfront payment of $200.0 million and will be eligible for additional payments totaling up to $265.0 million upon the achievement of certain commercial and development milestones for Fanapt(tm) in the U.S. and Canada. We will also receive royalties, which, as a percentage of net sales, are in the low double.digits, on net sales of Fanapt(tm) in the U.S. and Canada. In addition, we will no longer be required to make any future milestone payments with respect to sales of Fanapt(tm) or any future royalty payments with respect to sales of Fanapt(tm) in the U.S. and Canada. We retain exclusive rights to Fanapt(tm) outside the U.S. and Canada and we will have exclusive rights to use any of Novartis’ data for Fanapt(tm) for developing and commercializing Fanapt(tm) outside the U.S. and Canada. At Novartis’ option, we will enter into good faith discussions with Novartis relating to the co.commercialization of Fanapt(tm) outside of the U.S. and Canada or, alternatively, Novartis will receive a royalty on net sales of Fanapt(tm) outside of the U.S. and Canada. On February 23, 2010, the U.S. Patent and Trademark Office (PTO) issued a notice of allowance for our patent application for the long acting injectable (or depot) formulation of Fanapt(tm)
. The PTO has informed us that the application is eligible for patent term adjustment of an additional 300 days, making the patent expiration date August 26, 2023.On May 6, 2009, the FDA granted U.S. marketing approval of Fanapt(tm) for the acute treatment of schizophrenia in adults. On October 12, 2009, we entered into an amended and restated sublicense agreement with Novartis. We had originally entered into a sublicense agreement with Novartis on June 4, 2004 pursuant to which we obtained certain worldwide exclusive licenses from Novartis relating to Fanapt(tm)
. Pursuant to the amended and restated sublicense agreement, Novartis has exclusive commercialization rights to all formulations of Fanapt(tm) in the U.S. and Canada. On January 11, 2010, Novartis launched Fanapt(tm) in the U.S. We retain exclusive rights to Fanapt(tm) outside the U.S. and Canada and we will have exclusive rights to use any of Novartis’ data for Fanapt(tm) for developing and commercializing Fanapt(tm) outside the U.S. and Canada.Fanapt(tm) is a compound for the treatment of schizophrenia. On May 6, 2009, the FDA granted U.S. marketing approval of Fanapt(tm) for the acute treatment of schizophrenia in adults. On October 12, 2009, we entered into an amended and restated sublicense agreement with Novartis. We had originally entered into a sublicense agreement with Novartis on June 4, 2004 pursuant to which we obtained certain worldwide exclusive licenses from Novartis relating to Fanapt(tm)
. Pursuant to the amended and restated sublicense agreement, Novartis has exclusive commercialization rights to all formulations of Fanapt(tm) in the U.S. and Canada. On January 11, 2010, Novartis launched Fanapt(tm) in the U.S. Except for two post.approval studies started by us prior to the execution date of the amended and restated sublicense agreement, both of which were substantially completed by December 31, 2009, Novartis is responsible for the further clinical development activities in the U.S. and Canada, including the development of a long.acting injectable (or depot) formulation of Fanapt(tm)
. Pursuant to the amended and restated sublicense agreement, we received an upfront payment of $200.0 million and will be eligible for additional payments totaling up to $265.0 million upon the achievement of certain commercial and development milestones for Fanapt(tm) in the U.S. and Canada. We will also receive royalties, which, as a percentage of net sales, are in the low double.digits, on net sales of Fanapt(tm) in the U.S. and Canada. In addition, we will no longer be required to make any future milestone payments with respect to sales of Fanapt(tm) or any future royalty payments with respect to sales of Fanapt(tm) in the U.S. and Canada. We retain exclusive rights to Fanapt(tm) outside the U.S. and Canada and we will have exclusive rights to use any of Novartis’ data for Fanapt(tm) for developing and commercializing Fanapt(tm) outside the U.S. and Canada. At Novartis’ option, we will enter into good faith discussions with Novartis relating to the co.commercialization of Fanapt(tm) outside of the U.S. and Canada or, alternatively, Novartis will receive a royalty on net sales of Fanapt(tm) outside of the U.S. and Canada.Therapeutic opportunity
Schizophrenia is a chronic, debilitating mental disorder characterized by hallucinations, delusions, racing thoughts and other psychotic symptoms (collectively referred to as “positive symptoms”), as well as moodiness, anhedonia (inability to feel pleasure), loss of interest, eating disturbances and withdrawal (collectively referred to as “negative symptoms”), and additionally attention and memory deficits (collectively referred to as “cognitive symptoms”). Schizophrenia develops in late adolescence or early adulthood in approximately 1% of the world’s population. Most schizophrenia patients today are treated with drugs known as “atypical” antipsychotics, which were first approved in the U.S. in the late 1980s. These antipsychotics have been named “atypical” for their ability to treat a broader range of negative symptoms than the first.generation “typical” antipsychotics, which were introduced in the 1950s and are now generic. Atypical antipsychotics are generally regarded as having improved side effect profiles and efficacy relative to typical antipsychotics and currently comprise approximately 90% of schizophrenia prescriptions. Currently approved atypical antipsychotics include, in addition to Fanapt(tm) , olanzapine (Zyprexa®) by Eli Lilly and Company, risperidone (Risperdal®) and paliperidone (Invega®), each by Ortho.McNeil.Janssen Pharmaceuticals, Inc., quetiapine (Seroquel®) by AstraZeneca, aripiprazole(Abilify®) by Bristol.Myers Squibb (BMS), ziprasidone (Geodon®) by Pfizer, asenapine (Saphris®) by Schering.Plough and generic clozapine.
Pursuant to the amended and restated sublicense agreement, Novartis will be responsible for the further clinical development of the long.acting injectable or depot formulation of Fanapt(tm)
. The depot formulation is administered once every four weeks and we believe will be a compelling complement to the oral formulation for both physicians and patients. Novartis conducted a two.month Phase I/IIa safety trial of this formulation in schizophrenia patients, in which it demonstrated the benefit of consistent release over a four.week time period with no greater side effects relative to oral dosing. The commercial potential for the extended.release injectable formulation has been demonstrated by the success of the injectable formulation for risperidone, Risperdal® Consta® , which achieved worldwide sales of approximately $1.3 billion in 2008, according to Alkermes Company press releases. Intellectual property Fanapt(tm) and its metabolites, formulations, genetic markers and uses are covered by a total of twenty.two patent and patent application families worldwide. The primary new chemical entity patent covering Fanapt(tm) expires normally in 2011 in the U.S. and 2010 in most of the major markets in Europe. In the U.S., the United States Drug Price Competition and Patent Term Restoration Act of 1984, more commonly known as the “Hatch.Waxman Act” provides for an extension of new chemical entity patents for a period of up to five years following the expiration of the patent covering that compound to compensate for time spent in development. We believe that Fanapt(tm) will qualify for the full five.year patent term extension and, in addition, will be eligible for 6 months of pediatric exclusivity. In Europe, statutes provide for ten years of data exclusivity (with the potential for an additional year if the drug is developed for a significant new indication). No generic versions of Fanapt(tm) would be permitted to be marketed or sold during this 10.year (or 11.year) period in most European countries. Consequently, assuming that patent term restoration and pediatric exclusivity are granted by the PTO and FDA and that we receive regulatory approval in Europe, we expect that Novartis’ rights to commercialize Fanapt(tm) will be exclusive until May 2017 in the U.S. and for at least 10 years from approval in Europe. Additionally, the patent application covering the depot formulation of Fanapt(tm) , which Novartis will be responsible for, if it is granted, will expire normally in 2023 in the U.S. Several other patent applications covering metabolites, uses, formulations and genetic markers relating to Fanapt(tm) extend beyond 2020.
We acquired worldwide, exclusive rights to the new chemical entity patent covering Fanapt(tm) and certain related intellectual property from Novartis under a sublicense agreement we entered into in 2004, which was restated and amended in 2009. Please see “License agreements” below for a more complete description of the rights we acquired from and relinquished to Novartis with respect to Fanapt(tm)License agreements
We acquired exclusive worldwide rights to patents and patent applications for Fanapt(tm) through a sublicense agreement with Novartis. A predecessor company of sanofi.aventis, Hoechst Marion Roussel, Inc. (HMRI), discovered Fanapt(tm) and completed early clinical work on the compound. In 1996, following a review of its product portfolio, HMRI licensed its rights to the Fanapt(tm) patents and patent applications to Titan Pharmaceuticals, Inc. (Titan) on an exclusive basis. In 1997, soon after it had acquired its rights, Titan sublicensed its rights to Fanapt(tm) on an exclusive basis to Novartis. In June 2004, we acquired exclusive worldwide rights to these patents and patent applications as well as certain Novartis patents and patent applications to develop and commercialize Fanapt(tm) through a sublicense agreement with Novartis. In partial consideration for this sublicense, we paid Novartis an initial license fee of $0.5 million and were obligated to make future milestone payments to Novartis of less than $100.0 million in the aggregate (the majority of which were tied to sales milestones), as well as royalty payments to Novartis at a rate which, as a percentage of net sales, was in the mid.twenties. In November 2007, we met a milestone under this sublicense agreement relating to the acceptance of our filing of the NDA for Fanapt(tm) for the treatment of schizophrenia and made a corresponding payment of $5.0 million to Novartis. As a result of the FDA’s approval of the NDA for Fanapt(tm) , we met an additional milestone under this sublicense agreement which required us to make a payment of $12.0 million to Novartis.
On October 12, 2009, we entered into an amended and restated sublicense agreement with Novartis which amended and restated our June 2004 sublicense agreement with Novartis relating to Fanapt(tm) . Pursuant to the amended and restated sublicense agreement, Novartis has exclusive commercialization rights to all formulations of Fanapt(tm) in the U.S. and Canada. Novartis began selling Fanapt(tm) in the U.S. during the first quarter of 2010. Except for two post.approval studies started by us prior to the execution date of the amended and restated sublicense agreement, both of which were substantially completed by December 31, 2009, Novartis is responsible for the further clinical development activities in the U.S. and Canada, including the development of a long.acting injectable (or depot) formulation of Fanapt(tm)
. Pursuant to the amended and restated sublicense agreement, we received an upfront payment of $200.0 million and are eligible for additional payments totaling up to $265.0 million upon the achievement of certain commercial and development milestones for Fanapt(tm) in the U.S. and Canada. We will also receive royalties, which, as a percentage of net sales, are in the low double.digits, on net sales of Fanapt(tm) in the U.S. and Canada. In addition, we will no longer be required to make any future milestone payments with respect to sales of Fanapt(tm) or any future royalty payments with respect to sales of Fanapt(tm) in the U.S. and Canada. We retain exclusive rights to Fanapt(tm) outside the U.S. and Canada and we will have exclusive rights to use any of Novartis’ data for Fanapt(tm) for developing and commercializing Fanapt(tm) outside the U.S. and Canada. At Novartis’ option, we will enter into good faith discussions with Novartis relating to the co.commercialization of Fanapt(tm) outside of the U.S. and Canada or, alternatively, Novartis will receive a royalty on net sales of Fanapt(tm) outside of the U.S. and Canada.
We may lose our rights to develop and commercialize Fanapt(tm) outside the U.S. and Canada if we fail to comply with certain requirements in the amended and restated sublicense agreement regarding our financial condition, or if we fail to comply with certain diligence obligations regarding our development or commercialization activities or if we otherwise breach the amended and restated sublicense agreement and fail to cure such breach. Our rights to develop and commercialize Fanapt(tm) outside the U.S. and Canada may be impaired if we do not cure breaches by Novartis of similar obligations contained in its sublicense agreement with Titan for Fanapt(tm) .
We are not aware of any such breach by Novartis. In addition, if Novartis breaches the amended and restated sublicense agreement with respect to its commercialization activities in the U.S. or Canada, we may terminate Novartis’ commercialization rights in the applicable country and we would no longer receive royalty payments from Novartis in connection with such country in the event of such termination.●Tasimelteon Sleep Disorders, including CRSD P3 【2009】Tasimelteon, a compound for the treatment of sleep and mood disorders, including Circadian Rhythm Sleep Disorders (CRSD). In November 2006, we announced positive top.line results from the Phase III trial of tasimelteon in transient insomnia. In June 2008, we announced positive top.line results from the Phase III trial of tasimelteon in chronic primary insomnia. On January 19, 2010, the United States Food and Drug Administration (FDA) granted orphan drug designation status for tasimelteon in a specific CRSD, Non.24.Hour Sleep/Wake Disorder in blind individuals without light perception. The FDA grants orphan drug designation to drugs that may provide significant therapeutic advantage over existing treatments and target conditions affecting 200,000 or fewer U.S. patients per year. Orphan drug designation provides potential financial and regulatory incentives, including study design assistance, tax credits, waiver of FDA user fees, and up to seven years of market exclusivity upon marketing approval. We will continue to explore the path to a New Drug Application (NDA) for tasimelteon. Tasimelteon is also ready for Phase II trials for the treatment of depression. Given the range of potential indications for tasimelteon, we may pursue one or more partnerships for the development and commercialization of tasimelteon worldwide. ● 【2009】
●Vanda Pharmaceuticals,Inc[米] ●Development Pipeline FanaptmV (iloperidone) Tasimelteon(VEC-162) ■Investor Relations ●SEC Filings 10-K Annual report[2010.3.15] - [pdf,227p] - [doc] - [xls] ●Press Releases Vanda Pharmaceuticals Announces U.S. Patent Allowance for a Long-Acting Injectable Formulation of FanaptmV (iloperidone) in the U.S.[2010.2.25]
Fanapt(TM) Launches in the U.S.[2010.1.11]
Vanda Pharmaceuticals Announces Expiration of Hart-Scott -Rodino Waiting Period for Exclusive License of Fanapt(TM)[2009.12.1]
Vanda Pharmaceuticals Enters into an Exclusive License Agreement for the Commercialization and Development of Fanapt(TM) in the U.S. and Canada for the Treatment of Schizophrenia[2009.10.12]
FDA Approves Vanda Pharmaceuticals' Fanapt(TM) for the Treatment of Schizophrenia[2009.5.6]
New Insights into the Mechanism of Action of Antipsychotic Drugs[2009.3.10]
FDA Accepts Vanda Pharmaceuticals Iloperidone Resubmission and Sets New Action Date[2008.11.20]
Vanda Pharmaceuticals Announces Receipt of Not Approvable Letter From FDA for Iloperidone[2008.7.28]
Data Presented at the American Psychiatric Association (APA) Annual Meeting Demonstrate Iloperidone's Efficacy and Safety, With Low Rates of Movement and Metabolic Adverse Events[2008.5.6]
Genetic Variation Associated with Treatment Response in a Clinical Study of a New Atypical Antipsychotic FiaptamV (iloperidone)[2008.2.29]
Vanda Presents Phase III Iloperidone Efficacy Data[2007.12.12]
Vanda Pharmaceuticals Receives FDA Acceptance of Iloperidone New Drug Application[2007.11.27]
Vanda Pharmaceuticals Submits Iloperidone New Drug Application[2007.9.27]
Antipsychotic Iloperidone Results Show Favorable Akathisia Profile[2007.5.22]
Vanda Pharmaceuticals to Present Data on Iloperidone at the 2007 American Psychiatric Association Annual Meeting[2007.5.18]
Vanda Pharmaceuticals to Present at the Annual Meeting of the International Congress on Schizophrenia Research[2007.3.27]
Vanda Pharmaceuticals Confirms Iloperidone Efficacy With Positive Phase III Clinical Trial Results in Schizophrenia[2006.12.7]
Vanda Pharmaceuticals Completes Enrollment for Iloperidone and VEC-162 Phase III Trials Ahead of Schedule[2006.8.30]
■Vernalis Group plc
- http://www.vernalis.com/; 英国バイオ製薬企業 2003.9 British Biotech plc と合併。 2004.4.23 RiboTargetsを加え、３社統合。 BBPは成果を出せないまま赤字決算を続けてきた。 VernalisもFrovaのみ製品発売に成功。 片頭痛薬frovatriptanで知られる。 [Frova] in Elan 1998.10 Vernalis Group, plc.から北米地区のライセンスを受けた。 2001.11 FDA承認(急性片頭痛)。 2002.3 UCBと共同販促契約。 2002.5に発売。;License供与元Venalisに商品化権を戻す(2004.3.30) その結果ElanはVenalisから$55m受領し、ElanはUCBに$10m解約金を支払う予定。 ●決算 (￡000) 2003/12 2003/4 2002/12 2001/12 (8か月)
売上高 8,631 9,143 5,882 13,828
営業利益 (29,388) (36,249) (19,689) (11,408) 経常利益 (36,864) (34,245) (18,122) (11,182) 当期純利益 (34,219) (30,586) (16,063) ( 9,891)
Frova売上 $25.0 (2003年米国売上高$37.5m) *Elanは2004年度販売権をElanに戻す。 欧州はMenariniが販売し、独(Allegro)・オーストリア・英国などで販売。
●Vernalis Group plc ●Investors ★Press Releases～決算関連のみ ★Financial Reports ●Vernalis News ●R&D Centre - 各疾患別
■VeroScience, LLC[US]
- http://www.veroscience.com/; 1334 Main Road Tiverton, RI 02878 非上場
●VeroScience, LLC ●Drug Development ●Publications & Research
■Vertex Pharmaceuticals Inc[US]
-http://www.vrtx.com/ ; NASDAQ(VRTX); 130 Waverly Street, Cambridge, MA 02139; Tel: 617-444-6100 2009.03.12 ViroChem Pharma Incを買収 ～VCH-222 and VCH-759などC型肝炎治療薬を獲得。 ●会社決算●OUR PIPELINE /2011.2
($ milllion) 2010 2009 2008 2007 2006 (ロイヤリティ) 30,244 28,320 37,483 47,973 41,208 (提携収入) 113,126 73,569 138,021 151,039 175,148 収入合計 143,370 101,889 175,504 199,012 216,356 原価及び経費 計 839,447 715,901 638,212 618,804 445,394 うち研究開発費 637,416 550,274 516,912 519,227 379,715 うち販売・一般管理費 187,800 130,192 101,290 78,554 49,858 営業利益 (696,077) (614,012) (462,708) (419,792) (229,038) 当期純利益 (754,626) (642,178) (459,851) (391,279) (206,891) 従業員数[連結] 1,691 ●主要製品
Clinical
IndicationMechanism/Target Development
StageCollaborator(s) HCV Infection telaprevir (VX-950) HCV Infection HCV Protease Inhibitor NDA accepted with priority review designation granted Janssen Pharmaceutica, N.V.;
Mitsubishi Tanabe Pharma CorporationVX-222 HCV Infection HCV Polymerase Inhibitor Phase 2a
Cystic Fibrosis
VX-770 Cystic Fibrosis CFTR Potentiator Phase 3 Cystic Fibrosis Foundation Therapeutics Incorporated VX-809 Cystic Fibrosis CFTR Corrector Phase 2a Cystic Fibrosis Foundation Therapeutics Incorporated
Immune-mediated Inflammatory Diseases
VX-509 Rheumatoid
ArthritisJAK3 Inhibitor Phase 2a
Epilepsy
VX-765 Epilepsy Caspase-1 Inhibitor Phase 2a
●Telaprevir (VX-950) C型肝炎 【2010】
Janssen Pharmaceutica, N.V.とは、2006年6月に共同開発契約を締結。この時点ではVertexは北米の独占権を保持、開発は北米とJanssen支配地域。 Janssenは北米・極東以外の国での独占販売権を保持。
田辺三菱は、2004年6月に日本および特定の極東地域の販売権の権利獲得。Telaprevir, our lead drug candidate, is an orally-administered hepatitis C protease inhibitor that we have evaluated in treatment-naAsve and treatment-failure patients with genotype 1 HCV infection in combination with peg-IFN and RBV. Telaprevir works by inhibiting the NS3-4A serine protease, an enzyme necessary for HCV replication.
We have collaboration agreements with Janssen Pharmaceutica, N.V., or Janssen, a Johnson & Johnson company, and Mitsubishi Tanabe Pharma Corporation, or Mitsubishi Tanabe, relating to the development and commercialization of telaprevir. Pursuant to these agreements, we are responsible for the commercialization of telaprevir in North America, Mitsubishi Tanabe is responsible for the commercialization of telaprevir in certain Far East countries, including Japan, and Janssen is responsible for the commercialization of telaprevir in the rest of the world. Telaprevir was discovered in our collaboration, now ended, with Eli Lilly and Company. We expect to pay Eli Lilly certain royalties on future sales of telaprevir.
On November 23, 2010, the FDA received our NDA for telaprevir. In January 2011, the telaprevir NDA was accepted for filing by the FDA, and we received priority review designation. The FDA's target review completion date for telaprevir is May 23, 2011. The FDA's regulatory review process for the telaprevir NDA includes, among other things, a detailed review by the FDA of the data and information contained in the NDA, meetings and frequent communications between us and representatives of the FDA, and FDA inspections, including inspections of clinical trial sites and third-party facilities used to manufacture telaprevir. If applicable regulatory criteria are not satisfied, the FDA could refuse to approve or delay the approval of the telaprevir NDA. In addition, we have completed our New Drug Submission to the Therapeutic Product Directorate of Health Canada. Telaprevir was granted priority review in Canada. We are seeking to obtain approval for and launch telaprevir in Canada in the second half of 2011.
In December 2010, Janssen announced that the marketing authorization application, or MAA, for telaprevir was granted accelerated assessment by the European Medicines Agency, or EMA, in the European Union. Review under the accelerated assessment procedure is provided by the EMA for drug candidates of major therapeutic interest and shortens the timeframe for review by the EMA. In the first quarter of 2011, the EMA accepted the telaprevir MAA. Janssen is seeking to obtain approval for and launch telaprevir in the European Union in the second half of 2011.
Background: Prevalence and Treatment of Hepatitis C Virus Infection
Exposure to the hepatitis C virus often leads to chronic infection, although patients frequently do not have symptoms and are unaware that they have become infected. Over time, liver inflammation develops in many patients, which can progress to scarring of the liver, called fibrosis, or more advanced scarring of the liver, called cirrhosis. Patients with cirrhosis may go on to develop liver failure or other complications of cirrhosis, including liver cancer. The World Health Organization has reported that HCV infection is responsible for more than 50% of all liver cancer cases and two-thirds of all liver transplants in the developed world.
The World Health Organization has estimated that about 170 million people are chronically infected with HCV worldwide and that an additional 3 million to 4 million people are infected each year. The Centers for Disease Control and Prevention have estimated that approximately 3.2 million people in the United States are chronically infected with HCV. The Institute of Medicine has estimated the infected population to be between 2.7 million and 3.9 million people.
Our clinical development activities related to telaprevir are focused on genotype 1 HCV infection, which is the most prevalent form of HCV infection in the United States, the European Union and Japan. We believe that approximately 2.6 million patients in the United States have genotype 1 HCV infection. We believe that these patients include approximately 750,000 patients who already have been diagnosed with genotype 1 HCV infection and 1.8 million patients who remain undiagnosed.
In addition to being the most prevalent form of HCV infection, infection with genotype 1 HCV is the most difficult to treat of the primary HCV genotypes. The current standard treatment for infection with genotype 1 HCV, which was first approved in 2001, is a combination of peg-IFN and RBV, generally administered for 48 weeks. This treatment regimen is associated with significant side-effects, including fatigue, flu-like symptoms, rash, depression and anemia. Among patients who begin treatment, a significant percentage of patients infected with genotype 1 HCV fail to achieve a long-term sustained response to therapy. In a clinical trial conducted by another company, involving approximately 3,070 treatment-naAsve patients in the United States infected with genotype 1 HCV, between 59% and 62% of patients receiving peg-IFN and RBV failed to achieve an SVR. On an intent-to-treat basis, 56% of treatment-naAsve patients in the control arm of our Phase 3 ADVANCE clinical trial, who received the current standard treatment for genotype 1 HCV infection, failed to achieve an SVR. We believe that there are over 250,000 patients infected with genotype 1 HCV in the United States who have failed to achieve an SVR after therapy with peg-IFN and RBV.
Telaprevir Clinical Development
Our registration program for telaprevir included the REALIZE clinical trial, a Phase 3 clinical trial in patients infected with genotype 1 HCV who failed to achieve an SVR with prior interferon-based treatment, and two Phase 3 clinical trials, ADVANCE and ILLUMINATE, in treatment-naAsve patients infected with genotype 1 HCV.
REALIZE
REALIZE was a pivotal three-arm double-blinded placebo-controlled clinical trial of telaprevir-based treatment regimens that enrolled 662 patients with genotype 1 HCV infection who failed to achieve an SVR after treatment with peg-IFN and RBV. Patients were randomized 2:2:1 to the two telaprevir-based treatment arms and the control arm, respectively. REALIZE included the following patient groups: kﾎ null responderskﾀthose patients who experienced at week 12 of prior therapy less than a 2 log 10 reduction in HCV RNA levels;
kﾎ partial responderskﾀthose patients who experienced in their prior course of therapy at least a 2 log 10 reduction in HCV RNA levels at week 12, but who failed to achieve undetectable HCV RNA levels by week 24; and
kﾎ relapserskﾀthose patients who experienced undetectable HCV RNA levels at the completion of at least 42 weeks of prior treatment, but who relapsed after treatment ended.
REALIZE is the only Phase 3 clinical trial of an HCV protease inhibitor to date to enroll null responders. REALIZE's primary endpoint was SVR, defined as the percentage of patients who had undetectable HCV RNA levels both at the end of treatment and 24 weeks after the end of treatment, measured on an intent-to-treat basis. SVR was measured in each of the two telaprevir-based treatment arms compared to the control arm, as well as across the three subgroups of patients in the trial arms. One of the two telaprevir-based treatment arms evaluated a lead-in approach in which patients received four weeks of pre-treatment with peg-IFN and RBV before receiving telaprevir. Another objective of REALIZE was to explore the safety of telaprevir when dosed in combination with peg-IFN and RBV.
The following table sets forth the SVR rates on an intent-to-treat basis for patients in the control arm and the combined telaprevir-based treatment arms. In addition, the table includes a supplemental pooled analysis of the SVR rates on an intent-to-treat basis of the relapser and partial responder patients together, across both the control arm and the two telaprevir-based treatment arms combined. (以下略)
Relapsers Partial
RespondersNull Responders Overall All telaprevir-based treatment arms 86%
(245/286)57%
(55/97)31%
(46/147)65%
(346/530)Pooled Results: 78%
(300/383)Control arm 24%
(16/68)15%
(4/27)5%
(2/37)17%
(22/132)Pooled Results: 21%
(20/95)COMPETITION HCV Infection
Current HCV Market
A 48-week course of both peg-IFN, which requires weekly injections, and RBV, which is an oral drug, is the current standard treatment for genotype 1 HCV infection. This treatment regimen is associated with significant side-effects, including fatigue, flu-like symptoms, rash, depression and anemia. A majority of patients who begin treatment do not achieve an SVR. Based on discussions with physicians who treat patients infected with HCV, we believe that there are a significant number of patients with HCV who may consider treatment with new, more effective therapies.
Initial Anticipated Competitive Landscape for Telaprevir
Merck & Co., Inc.'s protease inhibitor, boceprevir, is the only HCV protease inhibitor that is being developed on a timeline comparable to telaprevir. Merck completed Phase 3 clinical trials of boceprevir-based treatment regimens in 2010. Merck announced in January 2011 the FDA had granted priority review of its NDA for boceprevir. As a result, we expect that boceprevir will be reviewed by the FDA on a very similar timeline to telaprevir and may be approved shortly prior to telaprevir. Merck's Phase 3 clinical trials of boceprevir included a clinical trial, RESPOND-2, that evaluated response-guided boceprevir-based triple combination therapy in treatment-failure patients but excluded null responders to prior treatment, and a clinical trial, SPRINT-2, that evaluated response-guided boceprevir-based triple combination therapy in treatment-naAsve patients. Merck reported results from these clinical trials in the second half of 2010. In November 2009, Merck initiated another Phase 3 clinical trial for boceprevir that it estimated would enroll approximately 660 patients infected with genotype 1 HCV to compare the effect on efficacy of erythropoietin use versus reducing the dose of RBV for the management of anemia.
If telaprevir and boceprevir are both approved on a comparable timeline, we believe that the drugs would compete in the marketplace based on, among other things, safety and efficacy data from their respective clinical trials, breadth of approved use, dosing regimen, cost, cost of co-therapies and side-effect profiles.
Long-term Competitive Landscape in HCV
We are aware of numerous other compounds in clinical trials that target HCV infection through a number of different mechanisms of action, and we believe that there are many additional potential HCV treatments in research or early development. There are a number of earlier-stage protease inhibitors, HCV polymerase inhibitors and HCV NS5A inhibitors, each of which is a direct-acting antiviral compound. We believe the most advanced of these compounds is TMC-435, a protease inhibitor being developed by Tibotec, an affiliate of our collaborator Janssen, and Medivir AB. In the first quarter of 2011, Tibotec initiated the first Phase 3 clinical trial of TMC-435. We believe that these earlier-stage drug candidates, if approved, would be launched several years after telaprevir. If any of these drug candidates is approved as a treatment for HCV infection, we expect that they would compete with telaprevir on the basis of the factors described above.
Future competition in the HCV treatment market may result from the administration of combinations of new oral therapies, and we are aware of a number of companies focusing on developing combinations of direct-acting antiviral compounds. We are conducting a Phase 2a clinical trial in which we plan to evaluate an all-oral combination of VX-222, our lead polymerase inhibitor, with telaprevir and RBV, but without peg-IFN. We are aware that many companies, including Abbot Laboratories, Bristol-Myers Squibb Company, Gilead Sciences, Inc., Intermune, Inc., Merck, Pharmasset, Inc., and Hoffman-La Roche, are seeking to develop combination regimens to treat HCV infection, including several combinations being evaluated in Phase 2 clinical trials.
●VX-222 C型肝炎 【2010】 ● 【2010】 ● 【2010】
●Vertex Pharmaceuticals Inc ■Our Medicines ★Approved Mediines Incivek ★Drug Candidate ■Investor Info ●SEC Filings 10-K annual report[2011.2.17] ■News
■Viropharma Inc[US]
(Nasdaq: VPHM). ViroPharma Incorporated to Acquire U.S. Vancocin Brand from Lilly[2004.10.18] 2008.10.21 バイオ製薬企業Lev Pharmaceuticals, Inc.を買収。Cinryzeを獲得。 ●会社決算●主要製品
($ 000) 2009 2008 2007 2006 2005 2004 2003 2002 2001 製品売上高 310,449 232,307 203,770 166,617 125,853 8,348 - - - 総収入 310,449 232,307 203,770 167,181 132,417 22,389 1,612 5,537 3,385 営業利益 32,130 78,655 115,796 98,806 88,145 (12,009) (33,966) (48,912) (79,183) 当期純利益 (11,077) 67,617 95,353 66,666 113,705 (19,534) (36,942) (26,623) (78,481) 研究開発費 52,083 66,280 35,869 19,162 10,610 16,388 23,043 39,823 43,013 従業員数[連結] 188 201 115 67 48 Vancocin 213,138 232,284(+14.0) 203,750(+22.3) 166,600(+32.4) 125,900 - - - - [vancomycin]2004.10 Lillyから承継 Cinryze 97,311 23 []
●Viropharma Inc ●Products ★Vancocin(R) (Vancomycin Hydrochloride Capsules, USP) to treat antibiotic-associated pseudomembranous colitis caused by Clostridium difficile infection (CDI), or C. difficile, and enterocolitis caused by Staphylococcus aureus, including methicillin-resistant strains. ★Cinryze(TM) C1 Inhibitor (human) - angioedema attacksの予防 patients with Hereditary Angioedema (HAE;遺伝性血管浮腫) ●Pipeline ●Media ●News 11/15/10 Cinryze(R) (C1 esterase inhibitor [human]) Data Presented at 2010 Annual Meeting of the American College of Allergy, Asthma & Immunology (ACAAI)
11/09/10 ViroPharma Announces Six Upcoming Presentations of Cinryze(TM) (C1 Esterase Inhibitor (Human)) Data at 2010 Annual Meeting of the American College of Allergy, Asthma & Immunology (ACAAI)
10/25/10 ViroPharma Announces Completion of Enrollment in Phase 2 Study Evaluating Subcutaneous Delivery of Cinryze(TM) (C1 Esterase Inhibitor [Human])
10/22/10 ViroPharma Receives Complete Response Letter for Cinryze(TM) (C1 Esterase Inhibitor [Human]) Industrial Scale Supplement
08/05/10 ViroPharma Announces Publication of Cinryze(TM) (C1 Esterase Inhibitor [Human]) Phase 3 Trial Results in Hereditary Angioedema (HAE) in the New England Journal of Medicine
06/21/10 ViroPharma Files Prior Approval Supplement (PAS) for Cinryze(TM) (C1 Esterase Inhibitor [Human]) Industrial Scale Manufacturing
05/17/10 ViroPharma Announces Availability of Cinryze(TM) (C1 Esterase Inhibitor [Human]) Final Open-Label Data
05/17/10 ViroPharma Introduces New Reconstitution System for Cinryze(TM) (C1 Esterase Inhibitor [Human])
04/27/10 ViroPharma Announces Initiation of Phase 2 Evaluation of Subcutaneous Delivery of Cinryze(TM) (C1 Esterase Inhibitor [Human])
03/31/10 ViroPharma Announces Initiation of Phase 2 Study of Cinryze(TM) (C1 Esterase Inhibitor [Human]) in Pediatric Patients
03/24/10 ViroPharma Announces Acceptance of Cinryze(TM) (C1 Esterase Inhibitor [Human]) Marketing Authorization Application (MAA) by European Medicines Agency (EMA)
03/19/10 ViroPharma Launches 'Ryze Above(TM)', A Personalized Patient Resources Program For Patients With Hereditary Angioedema (HAE)
03/19/10 Scientific Data Relating to Cinryze(TM) (C1 Esterase Inhibitor [Human]) Presented at First International Congress of the Southern European Allergy Society
02/24/10 ViroPharma Incorporated Reports Fourth Quarter and Full Year 2009 Financial Results
01/11/10 ViroPharma Provides 2010 Cinryze(TM) (C1 Esterase Inhibitor [Human]) Outlook
01/11/10 ViroPharma Expands Global Licensing, Commercialization and Development Rights for Cinryze(TM) (C1 esterase inhibitor [human])
06/04/09 ViroPharma Receives Complete Response Letter for Cinryze(TM) Supplemental Biologics License Application for Acute Treatment of Hereditary Angioedema
05/26/09 Scientific Data Relating to Cinryze(TM) Presented at 6th Annual C1 Inhibitor Deficiency Workshop
02/03/09 FDA Grants Priority Review of a Supplemental Biologics License Application for Cinryze(TM) C1 Inhibitor (Human) as Treatment for Acute Attacks of Hereditary Angioedema (HAE)
12/01/08 ViroPharma Submits Supplemental Biologics License Application for Cinryze(TM) to Treat Acute Attacks of Hereditary Angioedema
11/12/08 ViroPharma Announces Presentation of Cinryze(TM) Data in Acute Treatment of Hereditary Angioedema
10/30/08 ViroPharma to Discuss Commercialization and Launch of Cinryze(TM) on November 5, 2008
10/21/08 ViroPharma Incorporated Completes Acquisition of Lev Pharmaceuticals
- On May 2, 2008, the Blood Products Advisory Committee (BPAC) to the U.S. Food and Drug Administration (FDA) voted unanimously that there is sufficient evidence of the safety and efficacy for the approval of Cinryze for the prophylactic treatment of HAE. The data from Lev's acute treatment trial was not presented before the BPAC and is currently under active review at FDA. On May 6, 2008, Lev announced that FDA accepted for review Lev's complete response submission for Cinryze targeting an action date of October 14, 2008.
10/10/08 Cinryze(TM) Receives FDA Approval for Prophylaxis Against Hereditary Angioedema Attacks
●Lev Pharmaceuticals, Inc - Press REleases
Lev Pharmaceuticals to Submit Cinryze(TM) Application to the EMEA[2008.7.1]
Lev Pharmaceuticals Signs Agreements with CuraScript, CVS Caremark, and FFF Enterprises to Support Cinryze(TM) Commercialization[2008.6.4]
Lev Pharmaceuticals Announces Cinryze(TM) Complete Response Submission Accepted for Review by FDA [2008.5.6]
Lev Announces FDA Advisory Committee Unanimously Recommends Approval of Cinryze(TM) for Hereditary Angioedema [2008.5.2]
Lev Pharmaceuticals Announces Submission of Complete Response to FDA for Cinryze(TM) for Hereditary Angioedema [2008.4.15]
Lev Presents Results of Phase III Study Supporting Safety and Efficacy of Cinryze(TM) (C1 inhibitor) as Prophylactic Therapy for HAE [2008.3.18]
Lev Announces FDA's Blood Products Advisory Committee to Review Cinryze (TM) (C1 inhibitor) [2008.3.13]
Lev Pharmaceuticals Receives Complete Response Letter for Cinryze(TM)[2008.1.30]
Lev Presents Significant Data from Pivotal Phase III Trial of CinryzemV in Acute Treatment of Hereditary Angioedema at ACAAI Meeting [2007.11.11]
Lev Pharmaceuticals Amends CinryzemV BLA to Include Prophylactic Data [2007.10.30]
Lev’s CinryzemV BLA Accepted for Filing by FDA [2007.10.1]
Lev Pharmaceuticals Meets Primary Endpoint in Pivotal Phase III Prophylactic Trial for Hereditary Angioedema [2007.9.10]
Lev Pharmaceuticals Submits Biologics License Application for CinryzemV [2007.7.31]
Lev Pharmaceuticals Completes Phase III Prophylaxis Trial of C1-Esterase Inhibitor for Hereditary Angioedema [2007.5.31]
Lev Pharmaceuticals Reports Positive Results in Pivotal Phase III Trial for Hereditary Angioedema [2007.3.14]
Lev Pharmaceuticals' Drug Candidate for Hereditary Angioedema Focus of Broadcast News Story [2006.6.26]
ViroPharma Announces Meeting of FDA Advisory Committee for Pharmaceutical Science and Clinical Pharmacology on Bioequivalence Recommendations for Oral Vancomycin Hydrochloride Products[2009.5.29] - 諮問委は2009.8.4開催予定。Vancocin is the only approved product to treat Clostridium difficile-associated pseudomembranous colitis, one of the most common and devastating hospital-acquired infections. Clostridium difficile infection (CDI) can be severe, and without proper treatment, the associated complications of the disease can be deadly. The incidence of the disease observed in U.S. healthcare facilities more than doubled between 2000 and 2005; between 1999 and 2004, reported mortality rates from C. difficile in the U.S. more than quadrupled to 23.7 per million.ViroPharma Submits Comments on Vancocin(R) Draft Bioequivalence Guidance[2009.3.18] - Viropharma社はFDA's Office of Generic Drugs(OGD)に対しdraft guidance(2008.12制定) の取り下げを求めて新データを提出。 FDAは2006.3に一方的に生物学的同等性試験を人体からIn vitro溶出試験に変更。 2008.12のガイダンスでも同様。 public commentは2009年3月19日期限なので提出したもの。 ViroPharma Provides Update on Vancocin(R)[2008.12.15] - 新draft guidance ViroPharma Provides Update on Vancocin(R)[2008.1.8] - ViroPharma Submits Scientific Arguments in Supplement to Vancocin Petition for Stay of Action[2006.6.30] ViroPharma Files Supplement to Vancocin Petition for Stay of Action[2006.5.31] ViroPharma Announces Approval of Third Party Manufacturing and Supply Chain for Vancocin[2006.4.19] ViroPharma Further Comments on Vancocin[2006.3.17] ViroPharma Comments on Vancocin[2006.3.17] ViroPharma Licenses Rights to Develop Novel Therapeutic for Treatment of Clostridium Difficile-Associated Disease[2006.2.27] ViroPharma Incorporated to Acquire U.S. Vancocin Brand from Lilly[2004.10.18] ■Investors ●Annual Reports ●SEC Filings 10-K Annual Report[2010.2.25] - [pdf] - [doc] - [xls] 10-K Annual Report[2009.3.2] - [pdf] - [doc] - [xls]
■VIVUS, Inc[US]
性健康医薬品および肥満症製品に特化。 1991年 Delawareに設立 ●会社決算●パイプライン [2007]
($ 000) 2007 2006 2005 2004 2003 2002 2001 備考 製品売上高～米国 15,020(+5) 14,280(+22) 11,697 16,419 18,953 MUSE 製品売上高～国外 4,332(+82) 2,377(-15) 2,794 3,030 3,302 MUSE ライセンス等収入 35,346(+5,911) 588(+261) 163 152 5,183 主にEvamist 売上高計 54,698(+) 17,245(+) 14,654 19,601 27,438 営業利益 (1,454) (22,583) (25,285) (22,088) (1,118) 経常利益 2,711 (21,604) (24,459) (21,577) (345) 当期純利益 (2,384) (21,624) (24,484) (21,583) (26) 研究開発費 26,681 13,316 17,005 18,676 7,724 従業員数[連結] 111 MUSE世界売上 19,400(+16) 16,700(+15) [alprostadil]経尿道システム(勃起不全)米1997発売 ●主要製品概要
Product Indication Status Patent Expiry
and NumberQnexa (phentermine and topiramate) Obesity Phase 3 initiated 2019 (US 7,056,890 B2 ) Qnexa (phentermine and topiramate) Diabetes Phase 2 initiated 2019 (US 7,056,890 B2 ) Luramist (Testosterone MDTS) Hypoactive sexual desire disorder (HSDD) Phase 2 completed 2017 (US 6,818,226 ) Avanafil (PDE5 inhibitor) Erectile dysfunction (ED) Phase 2 completed 2020 (US 6,656,935 ●市場概要
●MUSE (2007) In 1997, we commercially launched MUSE in the United States. MUSE was the first minimally invasive therapy for erectile dysfunction approved by the FDA. With MUSE, an erection is typically produced within 15 minutes of administration and lasts approximately 30 to 60 minutes. Alprostadil is the active pharmacologic agent used in MUSE. Alprostadil is the generic name for the synthetic version of prostaglandin E1, a naturally-occurring vasodilator present in the human body and at high levels in seminal fluid. Because therapeutic levels of drug are delivered locally to the erectile tissues with minimal systemic drug exposure, MUSE is a relatively safe, local treatment that minimizes the chances of systemic interactions with other drugs or diseases. Over 13 million units of MUSE have been sold since we introduced MUSE to the market.
In May 2005, results were reported from an independent study conducted by the Cleveland Clinic, which focused on an individual's ability to restore sexual function following radical prostatectomy, a common treatment for prostate cancer. The study showed that 74% of patients who completed six months of MUSE treatment were able to resume sexual activity and 39% were able to achieve natural erections sufficient for intercourse.
We entered into an agreement granting Meda exclusive marketing and distribution rights for MUSE in member states of the European Union and we entered into an agreement granting Paladin Labs, Inc. exclusive marketing and distribution rights for MUSE in Canada. Meda currently sells MUSE in the United Kingdom, Ireland, Sweden, Norway, Germany, Switzerland, Denmark, Finland, France and the Netherlands. International product revenues from the sales of MUSE to these distributors is included in the financial statements and notes thereto appearing elsewhere in this Form 10-K. International sales are subject to certain additional risks inherent in conducting business outside the United States, including changes in overseas economic and political conditions, terrorism, currency exchange rates, foreign tax laws and tariffs and other governmental action.
Worldwide product revenues from the sales of MUSE were $19.4 million in 2007, an increase of $2.7 million, or 16%, from the worldwide sales of MUSE in 2006. Product revenue in the United States for the year ended December 31, 2007 was $15 million, as compared to $14.3 million in 2006. The increase in domestic revenues in 2007 is mainly due to increases in both domestic prices and shipment volume. Domestic demand for MUSE at the retail and government level remains consistent with the prior period, averaging approximately 200,000 units per quarter. Similar to prior years, wholesalers made purchases in the fourth quarter of 2007 that were greater than the current demand. Based on the fourth quarter demand for MUSE, we estimate purchases made by wholesalers in the fourth quarter of 2007 represent approximately 3 to 4 months of excess demand. The increase in international revenues in 2007 is mainly due to the timing of orders from our international distributors as well as adjustments to our sales allowance. The increase in license and other revenue is primarily due to the amortization of the deferred license revenue earned due to the sale of Evamist.
Worldwide product revenues from the sales of MUSE were $16.7 million in 2006, an increase of $2.2 million, or 15%, from the worldwide sales of MUSE in 2005. Product revenue in the United States for the year ended December 31, 2006 was $14.3 million, as compared to $11.7 million in 2005. The increase in revenues in 2006 was mainly due to increases in both domestic prices and shipment volume, partially offset by the timing of orders from our international distributors. The increase in other revenue is primarily due to the amortization of a $2 million milestone payment from our European distributor, Meda AB that we received in the first quarter of 2006.
Although the demand for MUSE has stabilized, given the loss of coverage under Medicare Part D, we are not able to anticipate if wholesalers will continue their historical pattern of making purchases in the fourth quarter that exceed expected quarterly demands. If wholesalers do not repeat this pattern of purchasing quantities of MUSE that exceed quarterly demands, revenues from the sale of MUSE in 2008 may be lower as compared to 2007.
●Luramist(TM) (Testosterone MDTS) (2007) Luramist(TM)(Testosterone MDTS) is our patent protected, transdermal investigational product candidate being developed for the treatment of HSDD in women. The active ingredient in Luramist is the synthetic version of the testosterone that is present naturally in humans. Luramist utilizes a proprietary, metered-dose transdermal spray, ("MDTS"), applicator that delivers a precise amount of testosterone to the skin. We licensed the U.S. rights for this product from Acrux in 2004. The metered spray enables patients to apply a precise dose of testosterone for transdermal delivery. The applied dose dries in approximately 60 seconds and becomes invisible. Acrux's independent studies have demonstrated that the Luramist system delivers sustained levels of testosterone in women over a 24-hour period and achieves an increasing number of satisfying sexual events.
We believe that our Luramist product candidate has significant advantages over patches and other transdermal gels that are being developed for this indication. The Luramist spray allows for discreet application, unlike patches that are visible and topical gels that can be messy. We believe that the patented MDTS delivery technology should prevent others from commercializing competitive therapies utilizing a spray delivery technology.
●Avanafil (2007) Avanafil is our orally administered, PDE5 inhibitor investigational product candidate, which we licensed from Tanabe Seiyaku Co., Ltd., ("Tanabe"), in 2001. We have exclusive worldwide development and commercialization rights for avanafil with the exception of certain Asian markets. Pre-clinical and clinical data suggests that avanafil: (1) is highly selective to PDE5, which we believe may result in a favorable side effect profile; (2) has a shorter plasma half-life than the current commercially available PDE5 inhibitors; and (3) is fast-acting.
Avanafil possesses a shorter plasma half-life than other PDE5 inhibitors currently on the market. The plasma half-life of a drug is the amount of time required for 50% of the drug to be removed from the bloodstream. We believe avanafil's short half-life and fast onset of action are ideal characteristics for the treatment of ED.
●Male Sexual Health (2007) Erectile dysfunction ("ED"), or the inability to attain or maintain an erection sufficient for intercourse, was reported by 35% of men between the ages of 40 to 70 in the United States, according to an independent study, with the incidence increasing with age. ED, frequently associated with vascular problems, is particularly common in men with diabetes and in those who have had a radical prostatectomy for prostate cancer. PDE5 inhibitors such as sildenafil citrate (Viagra(R)), vardenafil (Levitra(R)) and tadalafil (Cialis(R)), which inhibit the breakdown of cyclic guanosine monophosphate, have been shown to be effective treatments for ED. The worldwide sales in 2007 of PDE5 inhibitor products for ED were in excess of $3.5 billion, including approximately $1.8 billion in sales of Viagra, approximately $1.2 billion in sales of Cialis and approximately $495 million in sales of Levitra. Based on the aging baby boomer population and the desire to maintain an active sexual lifestyle, we believe the market for PDE5 inhibitors will continue to grow.
Significant competitive therapies exist for MUSE and avanafil in the form of oral medications marketed by Pfizer, Inc. under the name ViagraR, CialisR marketed by Eli Lilly and Company and LevitraR which is co-marketed by GlaxoSmithKline plc and Schering-Plough Corp in the United States.
Other treatments for erectile dysfunction exist, such as needle injection therapies, vacuum constriction devices and penile implants, and the manufacturers of these products will most likely continue to develop or improve these therapies. In November 2007, NexMed, Inc. announced that the NDA filed for its ED product, a topically applied alprostadil cream, was accepted for review by the FDA.
●Female Sexual Health (2007) We believe that the market for the treatment of sexual disorders in women is large and underserved. A paper published in the Journal of the American Medical Association in 1999 noted 43% of women between the ages of 18 and 59 identified themselves as afflicted with a sexual disorder, reporting hypoactive sexual desire disorder as one of the most common conditions of female sexual dysfunction, ("FSD"). Currently, there are no pharmaceutical treatments on the market that have been approved by the FDA for the treatment of FSD in women. Several companies are developing products that could compete with our investigational product candidates for the treatment of FSD including: The Proctor & Gamble Company is developing Intrinsa, a testosterone patch for the treatment of HSDD; BioSante Pharmaceuticals, Inc. is developing forms of testosterone gels for HSDD and Palatin Technologies, Inc. is developing a nasal spray to treat FSD. None of these products has been approved by the FDA. In July 2006, the European Medicines Agency ("EMEA") granted marketing authorization of Intrinsa for the treatment of HSDD in bilaterally oophorectomized and hysterectomized women and in February 2007, Intrinsa was launched in France and Germany. In March 2007, Intrinsa became available through the National Health Service ("NHS") in the United Kingdom.
●Hypoactive Sexual Desire Disorder("HSDD") (2007) Hypoactive Sexual Desire Disorder ("HSDD"), the persistent or recurrent lack of interest in sexual activity resulting in personal distress, is reported to be the most common type of female sexual dysfunction, affecting as many as 30% of women in the United States. Several studies over the last several decades have demonstrated that testosterone is an important component of female sexual desire. As a woman ages, there is a decline in testosterone production. The administration of testosterone has been associated with an increase in sexual desire in both pre- and post-menopausal women. In addition to the gradual decline in testosterone that accompanies aging and natural menopause, the surgical removal of a woman's ovaries rapidly results in a decrease of approximately one half of the woman's testosterone production capability. Hence, HSDD can occur much faster, and at a younger age, in women who have undergone this type of surgically induced menopause. Furthermore, HSDD has been observed in pre-menopausal women with naturally occurring low levels of testosterone. There are no FDA-approved medical treatments for HSDD; however, OB/GYNs have been prescribing Androgel(R), an approved testosterone treatment for hypogonadism in males. In addition, Intrinsa(TM), a transdermal testosterone patch, is currently approved and available for sale in Europe.
Double-blind, multi-center, placebo-controlled clinical trials conducted by The Procter & Gamble Company to assess the effects of Intrinsa (a twice-weekly testosterone patch) demonstrated a statistically significant increase in the number of satisfying sexual events in surgically induced menopausal women. In addition, an independent clinical study, conducted by Acrux in 261 patients, demonstrated that transdermally applied testosterone has the ability to improve sexual desire in pre-menopausal women with HSDD.
Our Clinical Candidate
Luramist(TM) (Testosterone MDTS) is our patent protected, transdermal investigational product candidate being developed for the treatment of HSDD in women. The active ingredient in Luramist is the synthetic version of the testosterone that is present naturally in humans.
In December 2004, an FDA advisory panel recommended against approval of a testosterone patch under development by another company to address female sexual dysfunction, specifically hypoactive sexual desire disorder. The FDA indicated that more safety data would be required before it would be in a position to recommend approval. Subsequently, this company withdrew its New Drug Application. We are developing a investigational transdermal testosterone product candidate, Luramist, which is designed to address hypoactive sexual desire disorder. In light of the FDA panel's recommendation, we may be required to undertake additional or expanded clinical trials, which could be expensive and the cause of significant delays in our ability to submit our investigational product candidate to the FDA for consideration. In the end, we may be unsuccessful in obtaining FDA approval of our investigational product candidate.
We are not permitted to market any of our investigational product candidates in the United States until we receive approval from the FDA. As a consequence, any failure to obtain or delay in obtaining FDA approval for our investigational product candidates would delay or prevent our ability to generate revenue from our investigational product candidates, which would adversely affect our financial results and our business.
●Obesity (2007) In 2004, the U.S. Centers for Disease Control and Prevention (the "CDC") ranked obesity as one of the top health threats in America. Obesity is a chronic condition that affects millions of people and often requires long-term or invasive treatment to promote and sustain weight loss. Obesity is the second leading cause of preventable death in the United States. The American Obesity Association estimates that approximately 127 million, or 64.5%, of adults in the U.S. are overweight, and an estimated 60 million, or 30.5%, are obese. According to a study performed by the CDC, as reported in the Journal of the American Medical Association, an estimated 112,000 excess deaths a year in the U.S. are attributable to obesity. The total direct and indirect costs attributed to overweight and obesity amounted to approximately $117 billion in 2000. Additionally, Americans spend more than $30 billion annually on weight-loss products and services. Current anti-obesity drugs include Xenical (orlistat), marketed by Roche, and Meridia (sibutramine), marketed by Abbott Labs. Orlistat works by inhibiting lipase, thus preventing digestion and absorption of dietary fat in the gastrointestinal tract. In 2007, Xenical accounted for approximately $70 million in sales in the United States. Orlistat was launched over-the-counter in the United States by GlaxoSmithKline under the brand name Alli, in June 2007. Phentermine is the largest selling anti-obesity therapeutic and is available in several generic forms. Topamax, marketed by Johnson and Johnson, is not approved for the treatment of obesity but analysts estimate Topamax is used for this indication in an off-label manner. Sanofi-Aventis' Acomplia (rimonabant) was approved in the European Union in 2006 for the treatment of obesity (the drug is approved in a total of 51 countries worldwide). However, Sanofi withdrew the drug's NDA in the United States following an FDA advisory panel's recommendation against approval on the basis of safety concerns.
There are several drugs in development for obesity including 4 product candidates in Phase 3 clinical trials being developed by Merck & Co., Inc., Pfizer, Arena Pharmaceuticals, Inc., and Orexigen Therapeutics, Inc., and approximately 20 product candidates in Phase 2 clinical trials by companies including Amylin Pharmaceuticals, Inc., Alizyme plc, Novo Nordisk and GlaxoSmithKline, among others.
In June 2007, an FDA advisory panel recommended against approval of Rimonabant, an oral obesity treatment targeting the CB1 receptor system being developed by another sponsor. Rimonabant is a centrally acting drug that reduces patients' desire to eat. The advisory panel expressed concerns about the impact of the drug on depressed patients and also expressed concerns about patients having thoughts about suicide. In addition, concerns about Rimonabant's mechanism of action and interference with the CB1 receptor pathway were also voiced. The sponsor of Rimonabant withdrew its NDA shortly after the advisory panel meeting.
●Diabetes (2007) Diabetes is a significant worldwide disease. Based on 2003 data, the International Diabetes Federation estimated that in 2005 there were 194 million adults with diabetes worldwide, an increase of over 40% since 1995. These figures included approximately 23 million in the United States and approximately 48 million in the European region. Approximately 90%, or 175 million, of diabetics worldwide suffer from type 2 diabetes, which is characterized by inadequate response to insulin and/or inadequate secretion of insulin as blood glucose levels rise. Therapies for type 2 diabetes are directed toward correcting the body's inadequate response with oral or injectable medications, or directly modifying insulin levels through injection of insulin or insulin analogs. The currently approved oral medications for type 2 diabetes include insulin releasers such as glyburide, insulin sensitizers such as Actos and Avandia, inhibitors of glucose production by the liver such as metformin, DPP-IV inhibitors like Januvia, as well as Precose and Glyset, which slow the uptake of glucose from the intestine. The worldwide market for diabetes medications exceeded $10 billion in 2004, of which oral drugs exceeded $6 billion. However, a significant portion of type 2 diabetics fail oral medications and require injected insulin therapy. Current oral medications for type 2 diabetes have a number of side effects, including hypoglycemia, weight gain and edema. Numerous pharmaceutical and biotechnology companies are seeking to develop insulin sensitizers, novel insulin formulations and other therapeutics to improve the treatment of diabetes. Previous clinical studies of topiramate in type 2 diabetics resulted in a reduction of hemoglobin A1c, a measure used to determine treatment efficacy of anti-diabetic agents. We are currently studying the impact of treating type 2 diabetics with Qnexa in an initial six-month Phase 2 study.
Prescription anti-diabetic drugs generate sales of more than $10 billion per year in the United States. We estimate there are several hundred anti-diabetic drug candidates currently being evaluated in clinical trials. New classes of drugs are being developed for type 2 diabetes including Byetta, a GLP-1 analog developed and marketed by Amylin Pharmaceuticals and Eli Lilly, which was approved by the FDA in April 2005. Byetta generated about $400 million in U.S. sales in 2006 and over $600 million in 2007. Januvia, a DPP-4 inhibitor, developed and marketed by Merck, was approved by the FDA in October 2006 and is experiencing a dramatic market growth thanks to its once-a-day oral dosing and perceived clean safety profile. Analysts have projected its sales to reach approximately $800 million in 2007. There are approximately 15 GLP-1 analogs/formulations and 25 DPP-4 inhibitors in clinical development today, dominated by large pharmaceutical companies. In addition, many companies are developing products against emerging drug targets in this therapeutic area.
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●VIVUS, Inc[US] ●Products Muse(R)(alprostadil) 経尿道システム (勃起不全) 米1997発売 Actis(R)(医療用具)Adjustable Constriction Loop ペニスを縛る紐様器具。 勃起不全 Evamist(TM)(estradiol transdermal spray) 更年期hot flash（ほてり） FDA承認2007.7.27。 K-V Pharmaceutical Company ("K-V") に2007.5.15 売却。 ●Research and Development ★Product Pipeline ●News Room ★Press Releases ●Healthcare Professionals ■Investors ●Financial Reports ●SEC Filings 10-K Annual report[2008.3.7] - [pdf,151p] - [doc] - [xls] ●Press Releases
■Warner Chilcott, Inc.[旧Galen Holdings]
- http://www.wcrx.com/; 本社Rockaway 80 Corporate Center, 100 Enterprise Dr., Ste. 280 Rockaway, NJ 07866 Galen時代は北アイルランド。 従業員数(英国・アイルランド)115(米)582(プエルトリコ)340 女性保健薬、皮膚疾患薬専門。 1968 Galen設立。 北アイルランド。 英国・アイルランドで医薬品販売。 1989 Vaginal ring を開発。 1997 London株式市場上場 2000 米国Nasdaq上場、Warner Chilcott plcを買収し事業継承。 2000.2 OVCON 経口避妊薬フランチャイズおよびESTRACE CreamをBristol-Myersから獲得。$180.0 million 2001.6 Estrace(R) tabletsをBristol-Myersから獲得。$95.0 million 2003 米国で女性保健薬に本格進出。 2003.3 Estrostep(R), Loestrin(R), 更に2003.4 femhrt(R)を$359 million＋up to $125.0 millionでPfizerから獲得。 2003.1 Sarafem(R)[premenstrual dysphoric disorder]の米国販売権をEli Lilly から$295 millionで獲得。 外用薬分野でDoryx[乾癬doxycycline pellet]を開発し、 Bristol-Myers SquibbとDovonex(R)[座瘡]の共同販売 契約およびLEO PHARMA A/SとDovobet(R)の開発契約 2004.3 Duramed Pharmaceuticals Incに、経口避妊薬LOESTRIN and MINESTRINの米国・カナダの独占販売権を許諾。$45.0 million 2004.3 Barr社との間に、当社製品OVCON 35のANDA申請しない契約を締結($20.0 million)したが、FTCの介入で破棄。 2004 Galen Holdings PlcからWarner Chilcott plcに社名変更＆本社移転。 2005.1.5 Warner Chilcott Holdings Company III,Limited が設立、同時にWarner Chilcott PLC.を買収。 決算期はWC PLCが９月だったが、WCHでは１２月。 2006.1 DOVONEXの米国内独占販売権をBMSより獲得。$205.2 million Warner Chilcott Limited (the “Company”) began commercial operations on January 5, 2005 when it acquir ed Warner Chilcott PLC (the “Predecessor”) (the “Acquisition”). The financial statements for all pe riods in 2005 reflect the Acquisition as if the closing took place on January 1, 2005 and the operating results for the period January 1 through January 4, 2005 were those of the Company. The Company is the direct parent of Warner Chilcott Holdings Company II, Limited (“Holdings II”), which is the direct p arent of Warner Chilcott Holdings Company III, Limited (“Holdings III”). ●会社決算●製品売上高
($ 000) 2007/12 2006/12 2005/12 2004/10-12 2004/9 2003/9 2002/9 2001/9 製品売上高 888,200(+18.1) 751,943 494,329 130,713 482,395
旧489,059他の収入 11,400(+352.2) 2,514 20,924 6,180 7,853
旧13,293総収入 899,561(+19.2) 754,457 515,253 136,893 490,248
旧502,352365,164 172,231 117,323 営業利益 経常利益 -47,291 -164,657 -569,768
旧-538,235-17,530 202,367
旧132,232127,670 52,523 5,927 当期純利益 28,875 -153,510 -556,646
旧-525,113-29,088 151,688
旧79,90096,155 145,176 16,426 研究開発費 54,510 26,818 58,636 4,608 26,558
旧24,47424,872 16,000 8,808 取得研究開発費 - - 280,700 - - - - 従業員数[連結] 985 945 *2005年売上高 (Successor) December 31, 2005期 *2004年売上高 (Predecessor)September 30, 2004期 from Annual Report 2003[2003.9決算期] Preliminary results for the year ended 30 September 2003[2003.11.11] 2003.1 Sarafem (fluoxetine hydrochloride) PMDD治療薬をEli Lillyより米国販売権取得(2002売上$80 million)。 2003.3 経口避妊薬Loestrin and Estrostep、同4月HRT薬femhrtをPfizerより取得。 2004.3 経口避妊薬Loestrinの独占販売権(米・加)をDuramed社に売却。 ●[2006 SEC Filingから] ★Competition ・ Hormonal Contraceptives－Johnson & Johnson (Ortho Tri-Cyclen R Lo, Ortho Evra R ), Bayer Schering Pharma A. G./Berlex Inc. (Yasmin R , Yaz R ), Akzo Nobel N.V./Organon (Nuvaring R ) and Duramed Pharmaceuticals, Inc. (Seasonique R ); ・Hormone Therapy－Wyeth (Premarin R , Premarin R Vaginal Cream, Prempro(TM) ), Novo Nordisk Pharmaceuticals, In c. (Activella R ), Bayer Schering Pharma A.G./Berlex Inc. (Climara R ) and Duramed Pharmaceuticals, Inc. (Cenestin R ); ・DORYX －Medicis Pharmaceutical Corporation (Solodyn R ), Bradley Pharmaceutical (Adoxa R ) and CollaGenex Pharmaceuticals Inc. (Oracea(TM) ); and ・Psoriasis －Galderma Laboratories, L.P. (Clobex R Spray) and Stiefel Laboratories, Inc./Connetics Corporation (Olux R Foam, Luxiq R Foam). ・ジェネリックとの競合 － OVCON, ESTRACE Tablets and ESTRACE Cream は特許が切れている。 2006.10 BarがOVCON 35のジェネリック発売。 2006.6 Watson Pharmaceuticals, IncがLOESTRIN 24 FE のANDA申請。
($ milllion) 2007/12 2006/12 2005/12 2004/10-12 2004/9 2003/9 備考 ★経口避妊薬 267.0(+16.8)[30%] 228.5[30%] 171.5(-7.5)[33%] 40.0[29%] 159.5(+29.0)[33%] 123.7 Ovcon 15.5(-79.0) 73.8(-18.1) 90.2(+26.1) 22.3 71.5(+22.1) 58.6(+29) (norethindrone and EE tablets, chewable)避妊薬 Estrostep 70.2(-31.9) 103.0(+26.7) 81.3(+31.8) 17.7 61.7(-) 26.5(-) 避妊薬&Acne(Norethindrone acetate &EE)(2003.3 Warner Chilcottより取得) Loestrin 148.9(+237.2) 44.2 - - 26.3 38.6(-) 避妊薬(Norethindrone acetate &EE) Pfizerより2003.3取得;米・加 FEMCON FE 32.4(+330.2) 7.5 - [チュアブル錠0.4mg norethindrone and 0.035mg ethinyl estradiol/ferrous fumarate]避妊薬 ★HRT 165.8(+13.0)[18%] 146.7(+6.8)[19%] 137.4(-9.5)[27%] 39.7[29%] 151.6(+64.6) 92.2 Estrace Tabs 9.7(+28.0) 7.6(-17.6) 9.2(-37.4) 3.6 14.7(-34.7) 22.5(+10) 更年期障害治療薬 Estrace cream 73.1(+11.2) 65.8(+22.1) 53.9(-7.3) 16.1 58.1(+29.8) 44.8(+23) 外用更年期障害治療薬 femhrt 63.7(+8.4) 58.7(-4.0) 61.2(-13.3) 16.3 70.5(-) 22.6(-) (Norethindrone acetate &EE)Pfizerより2003.4取得 Femring 15.5(+36.9) 11.3(+5.4) 10.7(+28.4) 3.7 8.3(-) 2.3(-) [estradiol acetate vaginal ring]更年期障害 Femtrace 3.8(+16.4) 3.3(+36.3) 2.4(+100) - - 更年期障害に伴うvasomotor症状(Estradiol acetate) ★外用薬 388.3(+25.4)[43%] 309.4(+223.0)[41%] 95.8[19%] 18.8[14%] 69.5[14%] Doryx 115.8(+13.0) 102.4(+6.9) 95.8(+37.9) 18.8 69.5(+28.4) 54.1(+28) [doxycycline pelletised製剤]ざ瘡(Acne) Dovonex 145.3(-1.1) 146.9 - - - - [calcipotriene]乾癬;2003.5から共同販売 Taclonex 127.2(+111.5) 60.1 - [軟膏calcipotriene 0.005% and betamethasone dipropionate 0.064%]乾癬; from LEO;米発売2006 ★PMDD 37.7(-0.6) 37.9(-8.8)[5%] 41.6[8%] 13.0[9%] 59.5[12%] Sarafem 37.7(-0.6) 37.9(-8.8)[5%] 41.6(-30.1)[8%] 13.0[9%] 59.5(-)[12%] 59.9(-) [paroxetine]Lillyより移管 ★その他 3.7(-53.8) 29.4 48.0 その他製品 3.7(-53.8) 8.6(-64.0) 23.5(-30.6) 7.8 34.0(-3.8) 35.3 受託製造 25.7(+23.2) 20.8(-15.1) 24.5(+195.3) 11.4 8.3(-) - ★製品売上高 計 888.2(+18.1) 751.9(+52.1) 494.3(+2.5) 130.7 482.4(+32.1) 365.2 Dovonex co-promotion 2.6(-88.0) 21.0(+169.2) 6.2 7.8(+100) - ●総収入 899.6(+19.2) 754.5(+46.4) 515.3(+5.1) 136.9 490.2(+34.3) 365.2
●Warner Chilcott, Inc. ●Products Atelvia®(risedronate sodium delayed-release tablets) ■Investor Relations ●Press Releases[2006/1～] Warner Chilcott Reports Operating Results for the Quarter and Year Ended December 31, 2010[2011.2.25] Operating Results End of Year 2005[pdf;2006.3.28] FDA Approves Taclonex(R)[pdf,2006.1.10] ●Quarterly Results Operating Results End of Year 2005[pdf,10p;200006.3.28] ●Annual Reports 2010 Annual Report 2009 Annual Report 2008 Annual Report Annual Report 2007 Annual Report 2006 ●SEC Filings 10-K annual report [February 25, 2011] 10-K annual report [March 1, 2010] 10-K annual report [April 17, 2009] 10-K annual report Warner Chilcott Limited[2007.2.29] 10-K annual report Warner Chilcott Limited[2007.3.26] Form 424B3 Prospectus Filed Pursuant to Rule 424[2006.4.25] ●Press Release[2003/5-2004/10] Warner Chilcott Reports Operating Results for the Quarter and Year ended December 31, 2007[2008.2.13] - [pdf] Operating Results End of Year 2005[2006.3.28] - [pdf] Warner Chilcott PLC Announces strong results for the fourth quarter ended 30 September 2004[2004.10.27] Galen Holdings PLC Name Change to Warner Chilcott PLC[2004.6.25] - 北米事業への主体移行により、社名変更。
■Watson Pharmaceuticals, Inc
１９８５年設立。 ジェネリック医薬品部門では全米第３位の売上規模、130製品(2002) 。 従業員数5,070(2008末)。 2006.3.13 Andrix Corporation (Nasdaq: ADRX) (全米第３位ジェネリック)を買収。 $1.9 Billion ★系列会社 Somerset Pharmaceuticals, (Watson Pharmaceuticals, Inc 50%; Mylan Laboratoriesとの合弁会社) ●会社決算*Generic /Brand売上区分の変更が実施されている。 経口避妊薬は、全米シェア第二位。16製品24規格。 * Oxytrol (oxybutynin) 2003.2 FDA承認; EMEA申請2003.3,CPMP勧告2003.11; UCBと販売契約(欧州),2003.9 *Distribution事業 2006年度からAndrix社買収後に開始した他社製造品の販売事業。 ●個別製品売上高
($ 000) 2009 2008 2007 2006 2005 2004 2003 2002 2001 備考 一般ジェネリック - - - 922,591(-2.5) 946,371(+35.2) 699,805 ジェネリック経口避妊薬 - - - 319,993(+9.2) 293,049(-6.0) 311,815 ジェネリック医薬品計 1,641,800 1,403,975 1,408,885 1,501,251 1,242,584(+0.3) 1,239,420(+22.5) 1,011,620(+17.2) 863,160 - - - - - - *659,277(+22.7) 537,450(-10.0) 597,398 その他 26,400 70,358 92,991 15,559 4,357(-76.6) 18,591(+13.3) 16,404 2006年Cephalon社代理店としてFentanyl販売手数料 ●ジェネリック事業 1,668,200 1,474,333 1,501,876 1,516,810 1,246,941(-0.9) 1,258,011(+22.4) 1,028,024 Specialty製品 14,100 - - 210,060(+7.2) 196,037(-17.0) 236,083(+55.1) 152,167 - Oxytrol/Trelstar 腎臓薬 7,700 - - 179,485(+7.0) 167,758(+4.3) 160,769(-6.3) 171,618 - 大半がFerrlecit/INFeD 銘柄医薬品計 393,700 397,025 375,202 354,070 389,545(+7.1) 363,795(-8.3) 396,852(+22.6) 323,785 - - - - - - - *749,195(+15.4) 649,495(+17.8) 551,558 その他 67,300 57,953 53,520 15,402 9,717(-48.2) 18,745(-42.9) 32,846 ●銘柄品事業 461,000 454,978(+6.1) 428,722 369,472 399,262(+4.4) 382,540(-11.0) 429,698 Distribution製品 663,800 606,190 566,053 92,796 - その他 - - - 166 - ●Distribution事業 663,800 606,190 566,053 92,962 - その他 - - - - 37,336(-24.2) 49,250(+35.9) 36,253(-209.3) 11,720 Royalty 売上 計 2,793,000 2,535,501 2,496,651 1,979,244 1,646,203(+0.3) 1,640,551(+12.5) 1457,722(+19.2) 1223,198(+5.4) 1160,676 粗利益 1,196,200 1,032,679 991,895 745,761 793,789 819,757 833,071 651,316 648,467 営業利益 383,900 358,128 255,660 (422,096) 218,512 265,940 338,913 269,364 101,319 Net Income 222,000 238,379 141,030 (445,005) 138,233 150,023 202,079 175,033 115,276 研究開発費 197,300(+16) 170,122 144,793 131,023 125,263(-6.7)[7.6%] 134,221[8.2%] 102,083(+24.2)[7.0%] 82,178 64,141 うち銘柄品 56,900 50,904 42,367 47,472 44,384(-31.7) 64,952(+32.4) 49,049 うちジェネリック 140,400 119,218 102,426 83,551 80,879(+16.8) 69,269(+30.6) 53,034 従業員数 5,830 5,070 3,983
($ million) 2009 2008 2007 2006 2005 2004 2003 2002 2001 備考 Oxytrol - - - - 38.4(+140) 15.8 発売=2003.4 [oxybutynin経皮パッチ]過活動膀胱 Ferrlecit - - - 145.4[81%] 134.0(+6.9)[80%] 125.4 [Sodium ferric gluconate in sucrose solution]鉄剤
●Watson Pharmaceuticals, Inc - http://www.watsonpharm.com/ ●Products ●Investors ★Financial Reports - Annual Reports 2008 Corporate Overview[2009.3.26] 2008 Form 10-K[2009.2.23] 2007 Annual Report[2008.3.26] Annual Report 2006[2007.5.4] Annual Report 2005[2006.4.1;pdf,116p] Annual Report 2004[2005.4.1;pdf,116p] Annual Report 2003[2004.1.1;pdf,83p] ★SEC Filings 10-K Annual report[2010.3.1] - [pdf,134p] - [doc] - [xls] 10-K Annual report[2009.2.23] - [pdf] - [doc] - [xls] 10-K Annual report[2008.2.25] - [pdf] 10-K Annual report[2007.3.1] - [pdf] 2005 Form 10-K[2006.3.10] -[pdf,113p](copy不可) -[xls] 2004 Form 10-K[2005.3.15;pdf,106p] copy不可 2003 Form 10-K[2004.3.12;pdf,106p] copy不可 ★Financial Releases ●Press Release Watson Reports Net Revenue of $786 Million for the Fourth Quarter 2009[2010.2.23] Watson Pharmaceuticals Reports Fourth Quarter and Full Year 2008 Results; Provides 2009 Outlook[2009.2.19] Watson Pharmaceuticals Reports Fourth Quarter and Full Year 2007 Results; Provides 2008 Outlook[2008.2.20] Watson Pharmaceuticals Reports Fourth Quarter and Full Year 2006 Results[2007.2.27] Watson Pharmaceuticals Reports Fourth Quarter and Full Year 2005 Results[2006.2.16] Watson Pharmaceuticals Reports Fourth Quarter and Full Year 2004 Results[2005.2.10] Watson Pharmaceuticals Reports Earnings Per Share Of $0.48 for Fourth Quarter 2003[2004.2.5] - 2003年度売上$1.46 billion(+19%; 前年度$1.22 billion) --------------------------- Watson Launches GELNIQUE(TM) (oxybutynin chloride) Gel 10%, First and Only Topical Gel for Overactive Bladder (OAB)[2009.5.21] - 最初で唯一の外よOAB治療薬。 従来製品が女性OAB患者の困惑と恥辱心を焦点にしたマーケティングに対し、 GELNIQUE(TM)を男性患者を含めて"power of control"を訴求する。 OAB患者数は米国で3400万人の成人。米OAB市場は年間$1.8 billionを超え増加傾向。 GELNIQUEは経皮剤なので口渇、便秘などの消化器症状を引き起こすfist-pass代謝経路をバイパスする。 主な副作用(2%以上)は、口渇と皮膚反応(5.4%) New Data Presented at AUA's Annual Conference Prove GELNIQUE(TM) (oxybutynin chloride) 10% gel is an Effective, Safe Option for Female Overactive Bladder (OAB) Patients[2009.4.27] - 789例１２週の試験で27%の女性の尿失禁(UI)を抑制した。プラセボは15.6%。 New, Published GELNIQUE Data Show Efficacy, Convenience and Excellent Tolerability[2009.3.16] - Watson Announces Positive Data for Its Investigational Oxybutynin Topical Gel for the Treatment of Overactive Bladder at SUNA's Annual Conference[2008.10.8] - Watson Announces Oxybutynin Topical Gel NDA Accepted for Filing by FDA for the Treatment of Overactive Bladder[2008.5.28] - Watson Announces Positive Data for Its New Investigational Products for Benign Prostatic Hyperplasia and Overactive Bladder[2008.5.21] - silodosinの心管系安全性およびoxybutynin chloride topical gel (OTG)の薬物動態 Watson Announces Positive Results From Its Pivotal Study of Oxybutynin Topical Gel for the Treatment of Overactive Bladder[2008.1.7] - --------------------------- Watson Files Lawsuit Against Barr for OXYTROL Patent Infringement[2008.10.24] - OXYTROL(R) (Oxybutynin Transdermal System)のジェネリック品のANDA申請提出したをBarr Pharmaceuticals, Inc.を提訴 Watson Notified of OXYTROL(R) Patent Challenge[2008.10.1] - WatsonはFDAからOXYTROL(R)のジェネリック品のANDA申請があったとの通告を受けた。 a Paragraph IV Certification Notice Letter 45日間以内に提訴することが認められる。 提訴した場合、Notice Letter受領から30ヵ月または地裁判決まで ANDA申請は保留される。 Health Canada Approves Watson Pharmaceuticals' OXYTROL(R) for the Treatment of Overactive Bladder[2004.6.23] Watson Pharmaceuticals' Transdermal Therapy for Urge Incontinence Approved for Marketing in the European Union[2004.6.21] - EU承認。for the symptomatic treatment of urge incontinence and/or increased urinary frequency and urgency Watson Pharmaceuticals Receives New Patent on OXYTROL(R)[2004.6.16] Watson Pharmaceuticals Enters Into Licensing Agreement With Paladin for OXYTROL(R) in Canada[2004.1.8] Watson Pharmaceuticals' OXYTROL(R) Receives Positive Opinion for Approval in the European Union[2003.11.24] - EMEA承認勧告。OXYTROL(R)は週２回投与。 Watson Pharmaceuticals Announces European Commercialization Agreement With UCB Pharma for OXYTROL(TM)[2003.9.24] - 欧州はUCB Pharmaに販売権。EU申請はWatson。 Watson's New Drug Submission for OXYTROL(TM) Accepted for Review in Canada[2003.5.23] Apr. 30, 2003 Data Presentations Support Efficacy and Tolerability of OXYTROL(TM)
(Oxybutynin Transdermal System) in Treating Women Suffering From Symptoms of Overactive Bladder Apr. 29, 2003 Percent Reduction in Urinary Incontinence Episodes Better Reflects Patient
Perception of Clinical Efficacy With OXYTROL(TM) Apr. 28, 2003 Watson Pharmaceuticals' OXYTROL(TM) Now Available Nationwide; Shipments to
More Than 45,000 Pharmacies - 最初で唯一のOAB外用剤として米国発売。主な対抗品はDetrol(R) LA, 4mg and Ditropan XL(R), 10mg. この経皮剤の特徴は、胃腸障害が経口剤により発生するのに対し、肝臓代謝をバイパスすることで避ける。 また４日間もの長期作用持続。 Mar. 18, 2003 Watson Pharmaceuticals & Ventiv Health, Inc. Announce U.S. Sales Force
Agreement for OXYTROL(TM) Mar. 11, 2003 Watson Pharmaceuticals Announces European Filing for OXYTROL(TM) - EU申請 Feb. 26, 2003 FDA Approves Watson's OXYTROL(TM), The First and Only Transdermal Therapy
for Overactive Bladder - Watson's NDA for Oxytrol(TM) in Overactive Bladder Accepted for Review by the FDA[2002.10.23] - Watson Pharmaceuticals Resubmits Oxytrol(TM) NDA for Overactive Bladder[2002.9.3] - Watson Pharmaceuticals Receives 'Not Approvable' Letter from the FDA For Oxytrol(TM)[2002.3.28] - FDAは追加臨床データを要求。 Watsonは最近終了したP3B試験データを申請に含めていなかった。 Watson Reports Oxytrol(TM) Phase III Study Results[2001.10.26] Watson Reports Phase III Study Results For Oxytrol(R), Its Transdermal Oxybutynin Patch[2001.8.14] Watson Announces Filing Of New Drug Application (NDA) For Oxybutynin Patch[2001.4.27]
■Xanodyne Pharmaceuticals, Inc
- http://www.xanodyne.com/ 設立 2001年
●Xanodyne Pharmaceuticals, Inc ●Products Zipsor(TM)(diclofenac potassium Liquid filled capsules) Oramorph SR(Morphine sulfate sustaines release tablets) ●Pipeline ●Newsroom XANODYNE ANNOUNCES FDA APPROVAL OF LYSTEDA (tranexamic acid) FOR TREATMENT OF WOMEN WITH HEAVY MENSTRUAL BLEEDING[2009.11.16]
Xanodyne's New Drug Application for the Treatment of Heavy Menstrual Bleeding (Menorrhagia) Accepted for Filing with a Priority Review Classification[2009.4.2]
Xanodyne Achieves Positive Efficacy Results in Pivotal Phase 3 Studies of Proprietary Modified Release Oral Tranexamic Acid Product Candidate for Heavy Menstrual Bleeding[2008.8.5]
■XenoPort, Inc
- http://www.xenoport.com/default.asp 設立 2001年 ●会社決算
($ 000) 2010 2009 2008 2007 2006 2005 (Joint活動収入) 1,364 24,758 28,981 104,898 - (提携収入) 1,515 9,515 13,015 8,924 10,606 総収入 2,879 34,273 41,996 113,822 10,606 研究開発費 52,546 70,747 83,172 74,397 65,434 販売・一般管理費 28,323 31,807 26,391 18,755 14,921 リストラ費用 5,275 - - - - 営業経費 合計 86,144 102,554 109,563 93,152 80,355 営業利益 (83,265) (68,281) (67,567) 20,670 (69,749) 経常利益 (82,469) (67,056) (62,946) 28,815 (64,313) 当期純利益 (82,469) (66,334) (62,540) 28,193 (64,313) 従業員数[連結] 108
●Gabapentin Enacarbil (Known as Horizant in the United States) kﾀ A Transported Prodrug of Gabapentin 【2010】
Our most advanced product candidate is being developed in Japan for the potential treatment of restless legs syndrome and in the United States for thepotential treatment of RLS and PHN. We hold composition-of-matter patents and methods-of-synthesis patents on Horizant in the United States andcomposition-of-matter patents on gabapentin enacarbil in Japan. We also hold patents or pending patent applications in the United States and outside theUnited States that are directed to the formulations and methods of synthesis and use of gabapentin enacarbil.Parent Drug Background
Gabapentin enacarbil is metabolized by the body to release gabapentin, a drug that has been sold by Pfizer Inc as Neurontin since 1993 and is currentlysold as a generic drug by a number of companies. Gabapentin is approved for marketing in the United States as adjunctive therapy in the treatment of partialseizures in patients with epilepsy and for the management of PHN. In addition, based on a variety of published medical studies, gabapentin is prescribed byphysicians to treat a wide range of psychiatric, neurological and pain conditions. Gabapentin has a side effect profile that is considered favorable, withdizziness and somnolence, or drowsiness, as the most commonly reported side effects.
Despite its substantial commercial success, we believe that gabapentin therapy can be significantly improved. Gabapentin absorption is highly variableamong patients, and there is a limit on the gabapentin exposure that can be achieved by direct oral administration of the parent drug. Published results fromclinical trials of gabapentin in epilepsy patients indicated that, for the same dose level, some patients absorbed as little as 10% of the dose of gabapentin administered while others absorbed more than 70%. We have also conducted a clinical trial of gabapentin in neuropathic painpatients in which the high variability of gabapentin absorption was confirmed. In addition, the short duration of gabapentin in blood after oral dosing requiresthat it be administered three times a day, which may lead to poor compliance with the dosing regimen and, therefore, reduced efficacy in some patients.
We believe that these suboptimal characteristics of gabapentin result from the mechanism responsible for the absorption of gabapentin. Gabapentin isactively transported across the GI tract after administration. However, the specific transporter mechanism responsible for gabapentin absorption appears tohave limited capacity, which seems to vary among individuals, and which is predominantly expressed in the upper GI tract. Due to gabapentin's poorabsorption in the lower GI tract, the use of traditional sustained-release formulations to correct the frequent dosing requirement has not been possible.
Our Transported Prodrug
Gabapentin enacarbil is designed to address the limitations of gabapentin by targeting high-capacity nutrient transporter mechanisms expressedthroughout the length of the intestinal tract. We believe that this approach can address the variable and suboptimal exposure to gabapentin experienced bypatients. By targeting transporters expressed throughout the length of the intestinal tract, we have been able to develop a sustained-release formulation ofgabapentin enacarbil that we believe provides more consistent absorption of gabapentin and has overcome the need for frequent dosing of gabapentin.
Gabapentin enacarbil is designed to rapidly convert to gabapentin once absorbed from the GI tract, resulting in limited systemic exposure to the intactTransported Prodrug. In addition to producing gabapentin, gabapentin enacarbil is metabolized to release other components with well-studied, favorablesafety characteristics. We believe that gabapentin enacarbil has demonstrated a favorable safety profile in clinical trials conducted in humans to date, whichprofile is comparable to that of gabapentin.
Phase 1 Clinical Trials
We have completed multiple safety, tolerability and pharmacokinetic Phase 1 clinical trials of gabapentin enacarbil. The results of these Phase 1 clinicaltrials indicated that all doses of gabapentin enacarbil were rapidly absorbed and converted to gabapentin, that doses up to 6000 mg produced dose-proportional gabapentin levels in the blood and that there was no evidence of saturation of drug absorption. Reported adverse events were consistent withthose reported previously for gabapentin; somnolence and dizziness were the most frequently reported adverse events. Exposure to the intact TransportedProdrug was low and transient compared to the level of gabapentin produced at all dose levels.
Initial Target Indications
Restless Legs Syndrome
Background on Restless Legs Syndrome. Restless legs syndrome is a neurological condition that causes an irresistible urge to move the legs. This urgeis usually accompanied by unpleasant sensations of burning, creeping, tugging or tingling inside the patients' legs, ranging in severity from uncomfortable topainful. These restless legs syndrome-related symptoms typically begin or worsen during periods of rest or inactivity, particularly when lying down or sitting,and may be temporarily relieved by movement such as walking or massaging the legs. Symptoms often worsen at night, and disturbed sleep is a commonresult of restless legs syndrome. Left untreated, restless legs syndrome may cause exhaustion, daytime fatigue, inability to concentrate and impaired memory.
Potential Markets. In the United States, GSK is seeking FDA approval for Horizant as a potential treatment of RLS. Although the exact prevalence rate of RLS is uncertain, a study published in Movement Disorders in 2010 indicated that approximately 2% of people in the United States are afflicted with RLS.
According to Datamonitor's 2008 Stakeholder Opinions: Restless Legs Syndrome report, there are approximately 8 million sufferers of RLS in the UnitedStates. We estimate that in 2010 there were approximately 4.6 million prescriptions written for drugs that are approved for the treatment of RLS in the UnitedStates.
In Japan, Astellas is seeking PMDA approval of gabapentin enacarbil as a potential treatment for restless legs syndrome. Although the exact prevalenceis uncertain, Astellas estimates that there are approximately 3.9 million patients with restless legs syndrome in Japan.
Current Treatments. In the United States, the currently approved and most widely prescribed treatments for RLS belong to a class of drugs calleddopamine agonists and include ropinirole (marketed as Requip by GSK), pramipexole (marketed as Mirapex by Boehringer Ingelheim GmbH) and genericcomparables of these drugs. Physicians also prescribe opioids, benzodiazepines and anticonvulsants, such as gabapentin, to treat patients with restless legssyndrome. In Japan, pramipexole was approved in 2010 for the treatment of restless legs syndrome.
GSK's U.S. Regulatory Filing. We evaluated Horizant in a Phase 3 clinical program for the treatment of RLS, and in January 2009, GSK filed anNDA with the FDA for Horizant as a treatment for RLS. In February 2010, GSK received a Complete Response letter from the FDA regarding the NDA forHorizant for RLS. In the Complete Response letter, the FDA concluded that the NDA provides substantial evidence of effectiveness for Horizant as atreatment for patients with RLS and that the FDA had not identified a clinical safety concern that would prevent approval of the 600 mg dose of Horizant.However, a preclinical signal of pancreatic acinar cell tumors in rats was determined to be of sufficient concern to preclude approval of the Horizant NDA forRLS at that time. In the Complete Response letter, the FDA acknowledged that similar preclinical findings were known for gabapentin, the parent drug of Horizant, at the time of the FDA's approval of gabapentin for refractory epilepsy, but concluded that the seriousness and severity of refractory epilepsy andthe benefit to patients provided by gabapentin justified the potential risk. In the Complete Response letter, the FDA also acknowledged that findings inlaboratory animals are not necessarily translatable to risk in humans, and the FDA noted that gabapentin products have been available for over 15 years andthey do not appear to be associated with a clinical signal for pancreatic cancer based on an analysis of spontaneous reports in the FDA's Adverse EventReporting System. However, the FDA concluded that the absence of a finding in analyses of post-marketing reports cannot be reliably interpreted as evidenceof the absence of risk.
In October 2010, GSK submitted its response to questions raised by the FDA in the Complete Response letter. GSK's response to the FDA includednew data from non-clinical studies of Horizant and two epidemiology studies, conducted by GSK, exploring gabapentin use and cancer based on the UKGeneral Practice Research Database. The resubmission also included a final safety update that provided updated or new safety information on patients inclinical studies who have been treated with Horizant. In order for the FDA to be able to consider published gabapentin non-clinical data in their assessment ofHorizant, GSK amended the NDA for Horizant from a Section 505(b)(1) to a Section 505(b)(2) application.
In November 2010, the FDA accepted for review GSK's response to the Complete Response letter for Horizant as a treatment of RLS. The FDAdesignated the resubmission as a Class 2 response and set a new PDUFA date of April 6, 2011.
XenoPort's Clinical Program. The Phase 3 clinical program encompassed multiple U.S. trials, including one 12-week, randomized, double-blind,placebo-controlled trial, known as the PIVOT (Patient Improvement in Vital Outcomes following Treatment) RLS I clinical trial (previously known asXP052), designed to evaluate the safety and efficacy of 1200 mg of Horizant versus placebo administered once a day at approximately 5:00 p.m., and asecond 12-week, randomized, double-blind, placebo-controlled trial, known as the PIVOT RLS II clinical trial (previously known as XP053), designed toevaluate the safety and efficacy of 600 mg or 1200 mg of Horizant versus placebo administered once a day at approximately 5:00 p.m. The co-primaryoutcome measures for these trials were defined to be the change from baseline in the International Restless Legs Syndrome, or IRLS, rating scale score andthe Investigator Clinical Global Impression of Improvement, or CGI-I, scale at the end of treatment. Secondary endpoints for both trials included onset ofefficacy and subjective sleep, pain, mood and quality of life assessments.
The PIVOT RLS I trial, which commenced in March 2006, enrolled 222 patients at 23 sites who were diagnosed with RLS. In April 2007, we reportedtop-line results demonstrating that treatment with 1200 mg of Horizant was associated with a statistically significant improvement in the co-primary endpointscompared to placebo. Improvements in the IRLS rating scale score were significantly greater for Horizant than for placebo (-13.2 vs. -8.8; p=0.0002). At theend of treatment, significantly more patients treated with Horizant were reported as "much improved" or "very much improved" on the Investigator CGI-Iscale compared to those treated with placebo (76% vs. 39%; p < 0.0001). During treatment over the 12-week period, the most commonly reported adverseevents for Horizant versus placebo were somnolence (27% Horizant; 7% placebo) and dizziness (20% Horizant; 5% placebo). There were no reported seriousadverse events in Horizant-treated patients.
The PIVOT RLS II trial, which commenced in August 2006, enrolled 325 patients who were diagnosed with RLS. In February 2008, we reported top-line results demonstrating that treatment with 1200 mg of Horizant was associated with a statistically significant improvement in the co-primary endpointscompared to placebo. Improvements in the IRLS rating scale score were significantly greater for 1200 mg of Horizant than for placebo (-13.0 vs. -9.8;p=0.0015). At the end of treatment, significantly more patients treated with 1200 mg of Horizant were reported as "much improved" or "very much improved"on the Investigator CGI-I scale compared to those treated with placebo (78% vs. 45% for placebo; p<0.0001).
This trial also demonstrated that treatment with 600 mg of Horizant was associated with a statistically significant improvement in the co-primaryendpoints compared to placebo. Improvements in the IRLS rating scale score were significantly greater for 600 mg of Horizant than for placebo (-13.8 vs.-9.8. p<0.0001). At the end of treatment, significantly more patients treated with 600 mg of Horizant were reported as "much improved" or "very muchimproved" on the Investigator CGI-I scale compared to those treated with placebo (73% vs. 45%, p<0.0001).
During the 12-week treatment period, the most commonly reported adverse events for Horizant were dizziness (24% 1200 mg Horizant; 10% 600 mgHorizant; 5% placebo) and somnolence (18% 1200 mg Horizant; 22% 600 mg Horizant; 2% placebo). These adverse events were generally mild or moderatein intensity. Withdrawals due to adverse events were 7% in the 1200 mg Horizant group, 6% in the 600 mg Horizant group and 6% in the placebo group.There were three reported serious adverse events in the study (one in the placebo group, two in the 600 mg Horizant group), none of which were considered treatment-related.
In addition to these two 12-week trials, the Phase 3 program also included a clinical trial, known as the PIVOT RLS Maintenance clinical trial(previously known as XP060), to assess the long-term efficacy of Horizant. The trial, which commenced in May 2006, was designed to evaluate the potentialof Horizant to maintain efficacy over the course of nine months in patients with RLS. The multi-center, double-blind, randomized, placebo-controlled,parallel-group clinical trial enrolled 327 patients diagnosed with RLS. All patients were administered 1200 mg of Horizant, taken at approximately 5:00 p.m.,for 24 weeks. Patients were assessed to determine treatment response at the end of this single-blind phase, and responders then entered the 12-week,randomized, double-blind phase of the clinical trial. Patients randomized to the placebo group received 600 mg of Horizant for two weeks and then receivedplacebo for an additional ten weeks. Patients randomized to the Horizant treatment group continued to receive 1200 mg of Horizant for the entire 12-week,double-blind period. In January 2008, we reported top-line results that showed that Horizant was generally well-tolerated during the treatment period and thatthere was a statistically significant difference between the percentage of patients treated with Horizant and placebo who met a pre-specified relapse criteriaduring the randomized phase of the study. Two hundred twenty one patients completed the 24-week, single-blind portion of the clinical trial, of which 194(88%) met the responder criteria and were randomized to double-blind treatment. Analysis of the primary endpoint indicated that treatment with Horizantresulted in a statistically significant lower proportion of relapses compared to placebo during the double-blind treatment period (23% placebo compared to 9%Horizant; p= 0.0158).
The most commonly reported adverse events during the single-blind phase of this clinical trial were somnolence (30%) and dizziness (22%), whichwere generally mild or moderate in intensity and transient in nature. The incidence of somnolence and dizziness in Horizant-treated patients during thedouble-blind portion of the trial were 3% and 2%, respectively. During the trial, there was one death that was determined to be unrelated to Horizanttreatment. There were five other serious adverse events, only one of which was judged as possibly related to Horizant treatment.
We have also conducted clinical trials and collected information that is typically required for submission of an NDA to the FDA, including anexamination of the exposure/response relationship, pharmacokinetics in a special population, drug/drug interactions, cognition, driving performance andcardiovascular safety. In addition, we have completed an open-label safety extension study that included patients from the two 12-week clinical trials toenable assessment of the safety of Horizant treatment extending up to 12 months. Data from this trial was also included in the NDA filing. The results of thePhase 3 clinical trials, combined with the results from other Horizant clinical trials in RLS patients, are intended to meet the International Committee forHarmonization, or ICH, guidelines for safety assessment.
In addition, GSK conducted a polysomnography, or sleep laboratory measurement, study of Horizant in RLS patients to explore further the potentialsleep benefits of Horizant. Results from this trial showed statistically significant benefits of Horizant versus placebo in several objective measurements ofsleep.
Astellas' Clinical Program and Regulatory Filing. In March 2009, Astellas reported results from a Phase 2 clinical trial of gabapentin enacarbil forthe treatment of symptoms in restless legs syndrome patients in Japan. The trial was a 12-week, double-blind, placebo-controlled study that enrolled 474patients who were diagnosed with restless legs syndrome. Patients were treated with 600, 900 or 1200 mg of gabapentin enacarbil or placebo, given once perday after the evening meal. The primary endpoint for the clinical trial was the change from baseline for the IRLS rating scale score at end of treatment.
Treatment with 1200 mg of gabapentin enacarbil was associated with a statistically significant improvement in the primary endpoint compared toplacebo. Statistically significant improvements over placebo were also observed on some secondary endpoints, including the investigator-rated CGI-I scale,which achieved statistical significance for each of the 600 mg, 900 mg and 1200 mg dosing cohorts.
The most commonly reported adverse events for gabapentin enacarbil were somnolence and dizziness, which were generally transient and mild tomoderate in severity. There were no treatment-emergent serious adverse events during the study period in gabapentin enacarbil-treated subjects.
In November 2009, Astellas filed an NDA with the PMDA for approval of gabapentin enacarbil as a potential treatment for restless legs syndrome in Japan. The evidence of efficacy for the NDA filing was based on data from Astellas' successful Phase 2 trial in restless legs syndrome patients conducted in Japan and our clinical program conducted in the United States.
Neuropathic Pain
Background on Neuropathic Pain. Neuropathic pain is pain that results from damage to nerves. The damage may result from a variety of causes,including injury or illnesses such as diabetes, HIV and shingles. In addition, the toxic effects of therapy used to treat patients with cancer or HIV may alsocause nerve damage leading to neuropathic pain.
One form of chronic neuropathic pain is PHN. PHN is a complication of shingles, a painful outbreak of rash or blisters on the skin caused by areactivation of the same virus that causes chicken pox. PHN is often characterized as constant stabbing, burning or electric shock-like sensations in the areaaffected by shingles after the rash has cleared. Approximately 10% to 15% of all patients with shingles develop PHN, which can persist for many years. DPNis another form of neuropathic pain that is associated with a family of nerve disorders caused by diabetes. Over time, people with diabetes can experiencedamage to nerves leading to numbness and sometimes pain and weakness in the hands, feet and legs.
Potential Market. We estimate that the prevalence of PHN is less than 200,000 patients in the United States. In May 2006, Merck & Co. receivedFDA approval for Zostavax, a live attenuated vaccine, to help prevent shingles. In October 2006, the U.S. Centers for Disease Control and Prevention'sAdvisory Committee on Immunization Practices voted unanimously to recommend that adults 60 years of age and older be vaccinated with Zostavax for theprevention of shingles. While Zostavax is not a treatment for shingles or PHN, the availability of this vaccine could impact the future market for therapies forPHN.
Diabetes is the leading cause of neuropathy in the Western world, and neuropathy is the most common complication and greatest source of morbidityand mortality in diabetes patients. In 2007, the National Institute of Diabetes and Digestive and Kidney Diseases estimated that 17.9 million people in the United States had been diagnosed with diabetes. Epidemiologystudies indicate that about 20% of community-dwelling diabetes patients suffer from DPN, indicating that approximately 3.5 million people in the UnitedStates are afflicted with DPN.
Current Treatments. Current classes of drugs used to treat patients with neuropathic pain include anticonvulsants, antidepressants and tricyclic drugs,with anticonvulsants representing the largest share of the neuropathic pain market. Of the anticonvulsants, gabapentin is the market leader, and pregabalin(marketed as Lyrica by Pfizer) is also widely prescribed for the treatment of neuropathic pain. Duloxetine (marketed as Cymbalta by Eli Lilly and Company)is an antidepressant that is also prescribed for the treatment of DPN. Also, the FDA recently approved a once-daily formulation of gabapentin (known asGralise from Depomed Inc. and its partner for pain indications, Abbott Laboratories) for PHN. Other treatments used in selected patients include a capsaicinpatch (marketed as Qutenza by NeurogesX, Inc.) and local application of lidocaine.
Phase 2 Clinical Trial Results. We have completed a randomized, double-blind, parallel, placebo-controlled Phase 2a clinical trial of Horizant for themanagement of PHN. The trial included 101 patients at 18 clinical sites in the United States. The objective of this trial was to assess the safety, tolerability,pharmacokinetics and efficacy of 1200 mg of Horizant administered twice a day for 14 days and to compare the response to Horizant against the response to placebo. The trial included a Neurontin treatment phase to enable the evaluation of blood levels of Neurontin.
The trial met the primary endpoint of the study, demonstrating that treatment with Horizant was associated with a statistically significant reduction inpain as measured by an 11-point numerical pain scale compared to placebo (p=0.032). Additional analyses were conducted on data from those patients whoreceived both Neurontin and Horizant. When administered Horizant, patients experienced on average a 17% increase in the steady-state average bloodconcentration of gabapentin compared to a dose of Neurontin that contained roughly 50% more gabapentin (p=0.005), indicating higher bioavailability ofHorizant. Thirty-six percent of evaluated patients had an increased steady-state average blood concentration of greater than 30%. For all patients who receivedHorizant, the change in average pain score between the last seven days of the Horizant treatment from the final seven days of Neurontin treatment wasdetermined. A statistically significant reduction in pain score at the end of Horizant treatment was observed (p=0.045). Horizant was well-tolerated. The mostcommon adverse event in the Horizant treatment group was dizziness, which was mild to moderate in severity.
GSK has evaluated Horizant in two Phase 2 clinical trials for the potential treatment of PHN. In September 2009, GSK announced top-line results froma 14-week, double-blind, placebo-controlled Phase 2b clinical trial that enrolled 376 subjects with PHN who had been experiencing pain for at least threemonths following healing of the herpes zoster skin rash. Subjects were randomized to receive placebo, 1200, 2400 or 3600 mg/day of Horizant divided intotwice-daily doses. The primary endpoint of the trial was the change from baseline to the end of maintenance treatment in the 24-hour average pain intensityscore. All doses of Horizant demonstrated statistically significant improvements over placebo on the primary endpoint, with the adjusted mean change frombaseline in the 24-hour average pain intensity score of -1.66 for placebo, -2.47 for 1200 mg/day Horizant, -2.36 for 2400 mg/day Horizant and -2.72 for 3600mg/day Horizant. The pre-specified statistical analysis included adjustment for comparisons of multiple Horizant doses to placebo. The adjusted p-values forcomparison of 1200, 2400 and 3600 mg/day to placebo were 0.013, 0.029 and 0.002, respectively. Horizant was generally well tolerated at all doses in thistrial. The most common adverse events were dizziness (17% 1200 mg Horizant, 26% 2400 mg Horizant, 30% 3600 mg Horizant and 15% placebo) andsomnolence (10% 1200 mg Horizant, 11% 2400 mg Horizant, 14% 3600 mg Horizant and 8% placebo), and most of these adverse events were mild ormoderate in intensity. Withdrawals due to adverse events were 6% in the 1200 mg Horizant group, 15% in the 2400 mg Horizant group, 18% in the 3600 mgHorizant group and 13% in the placebo group. There was one serious adverse event (gastritis) in the 3600 mg/day dose group that was judged by theinvestigator to be related to treatment.
In October 2009, GSK announced top-line results from a double-blind, two-period, cross-over Phase 2 clinical trial that enrolled 138 subjects diagnosedwith PHN who had been experiencing pain for at least three months following healing of the herpes zoster skin rash. Subjects with a history of inadequateresponse to gabapentin entered a baseline period during which they received a dose of 1800 mg/day of gabapentin for two weeks. Subjects (N=96) who had a24-hour average pain intensity score of at least four on the 11-point pain intensity rating scale were then randomized to receive either 1200 mg/day of Horizant for the first 28-day treatment period followed by 3600 mg/day for thesecond 28-day treatment period, or 3600 mg/day followed by 1200 mg/day. Subjects received 2400 mg/day of Horizant for four days in between the twotreatment periods. The primary endpoint in this trial was the change from baseline to the end of the treatment period in the 24-hour average pain intensityscore. A greater reduction in the 24-hour average pain score was observed for the 3600 mg/day dose than for the 1200 mg/day dose, which reduction wasstatistically significant. Horizant was well tolerated at both doses in this study. The only treatment-emergent adverse event occurring in greater than or equalto 5% of subjects taking Horizant was nasopharyngitis.
GSK has also evaluated Horizant for the potential treatment of DPN. In April 2009, GSK completed a 14-week, double-blind, placebo-controlled,Phase 2 clinical trial of Horizant as a potential treatment for DPN patients. In the trial, 421 patients who were diagnosed with either Type 1 or Type 2 diabetesmellitus with signs and symptoms of DPN were randomized to receive either 1200 mg/day, 2400 mg/day or 3600 mg/day of Horizant administered in divideddoses taken twice daily, 300 mg/day of pregabalin as an active control, administered in divided doses three times daily, or placebo. Neither Horizant norpregabalin, the active control, demonstrated a statistically significant improvement on the primary endpoint when compared to placebo, based on the changefrom baseline to end of treatment on the 24-hour average pain intensity score, which may have been a consequence of the unexpectedly high placebo responserate observed in the study. The highest dose of 3600 mg/day of Horizant showed consistent trends towards efficacy across multiple pain endpoints. Horizantwas generally well tolerated; the two most frequently reported adverse events were dizziness and somnolence.
Clinical Development of Horizant in Neuropathic Pain. The development of Horizant as a potential treatment for PHN has been delayed based on theFebruary 2010 Complete Response letter for RLS. GSK intends to have discussions with the FDA regarding the filing of an NDA, including the possibility of pursuing a Section 505(b)(2) NDA regulatory pathway, for Horizant as a potential treatment of PHN. Although we do not have active development programsunderway, we continue to evaluate our resources and potential for pursuing development of Horizant in the United States for the potential treatment of DPN,the potential treatment of PHN, to the extent that a product label would reflect a superiority claim over a currently approved drug, and for any additionalpotential indications.
Horizant/Gabapentin Enacarbil Development, Commercialization and Partnering Strategy
Due to the large market potential for Horizant, the requirement of a primary care physician sales force to address these markets in the United States andour desire to focus our commercialization efforts in the United States, we have entered into agreements with pharmaceutical partners to maximize thepotential commercial value of Horizant. In December 2005, we entered into a license agreement with Astellas for exclusive rights to develop andcommercialize gabapentin enacarbil in Japan and five Asian countries. Astellas made an up-front payment to us of $25.0 million, has paid additional milestones of $23.0 million and may make additional milestone payments to us of up to $37.0 million. We will receive royalties on any net sales of gabapentin enacarbil in the Astellas territory. Under the terms of the agreement, Astellas is responsible for all futuredevelopment costs and Astellas is solely responsible for the manufacturing of gabapentin enacarbil to support its development and commercialization withinthe Astellas territory. Astellas may terminate the collaboration at its discretion. In such event, all gabapentin enacarbil product rights would revert to us andwe would be entitled to specified transition assistance from Astellas.
Additionally, in February 2007, we announced an exclusive collaboration with GSK to develop and commercialize Horizant/gabapentin enacarbilworldwide, excluding the Astellas territory. In November 2010, we amended and restated our collaboration agreement with GSK, pursuant to which wereacquired all rights to gabapentin enacarbil outside of the United States previously granted to GSK (which excludes the Astellas territory) and obtained theright to pursue development of Horizant for: (i) the potential treatment of DPN; (ii) the potential treatment of PHN, to the extent that a product label wouldreflect a superiority claim over a currently approved drug; and (iii) any additional indications in the United States. GSK remains responsible for seekingapproval of the NDA for RLS in the United States, further development and regulatory matters with respect to Horizant for the potential treatment of PHN,possibly seeking NDA approval through a 505(b)(2) approval process, and commercialization of Horizant in the United States for all indications.
Under the terms of the amended and restated collaboration agreement, the aggregate clinical and regulatory milestone payments that we are eligible toreceive, have been increased by $37.5 million from a total of $275.0 million to $312.5 million, of which $85.0 million has been received to date. We remaineligible to receive up to an additional $290.0 million upon the achievement of specified sales levels; however, the associated sales levels that give rise to thesepayments were lowered from the terms of our original agreement.
We plan to enter into additional agreements with pharmaceutical companies for the development and commercialization of gabapentin enacarbil outsidethe United States and the Astellas territory to the extent that we are able to find partners and negotiate agreement terms that are suitable to us.
Marketing and Sales
Under the terms of our agreement with GSK, we have co-promotion rights for Horizant in the United States. Pending FDA approval of Horizant, GSKis responsible for: establishing pricing and reimbursement; creating promotional and advertising materials; managed care contracting; receiving, accepting andfilling orders; distributing; controlling invoicing, order processing and collecting accounts receivable; and recording sales of Horizant in the United States.Under the agreement, we can delay the deployment of our sales force for up to three years following the potential approval of Horizant in the United States.We may terminate our co-promotion right at any time upon notice to GSK with no penalty to us, resulting in a compensation structure based on a royalty ofGSK's sales of Horizant.
If gabapentin enacarbil is approved within the Astellas territory, Astellas will be responsible for all commercial activities related to the marketing andsale of gabapentin enacarbil.
We plan to establish additional development and commercialization partnerships with pharmaceutical and biotechnology companies to accelerate thecompletion of regulatory approval and product introduction and to maximize the breadth of the commercial opportunity of our other product candidates.
We also plan to license to third parties for development, marketing and sales other potential drug candidates that are discovered by us but do not fallwithin the CNS therapeutic area, our primary area of interest.
Competition
Horizant/Gabapentin Enacarbil. We anticipate that, if approved in the United States for RLS, Horizant will compete with currently approvedtreatments for RLS that all belong to a class of drugs called dopamine agonists, including the following: ropinirole (marketed as Requip by GSK); genericropinirole (marketed by, among others, CorePharma, LLC, Mylan Pharmaceuticals Inc. and Wockhardt USA LLC); pramipexole (marketed as Mirapex byBoehringer Ingelheim); and generic pramipexole (marketed by, among others, Teva, Norvartis AG and Watson Pharmaceuticals, Inc.). In addition, we couldalso experience competition from the rotigotine transdermal system (a dopamine agonist patch marketed as Neupro by UCB). UCB filed its NDA for thetreatment of RLS with the FDA in 2007. In April 2010, the FDA provided UCB a Complete Response letter that recommended reformulation of rotigotinebefore making it available in the U.S. market for the treatment of restless legs syndrome.
We anticipate that, if gabapentin enacarbil is approved in Japan forthe treatment of restless legs syndrome, it will compete with pramipexole, which was approved in 2010 for the treatment of restless legs syndrome.We anticipate that, if approved for neuropathic pain in the United States, Horizant would compete with generic gabapentin (marketed by Alpharma,IVAX Corp., Pfizer and Teva, among others). Other drugs targeting neuropathic pain will represent substantial competition. These include pregabalin(marketed as Lyrica by Pfizer), duloxetine (marketed as Cymbalta by Eli Lilly) and a capsaicin patch (marketed as Qutenza by NeurogesX, Inc.). Transdermalpatches containing the anesthetic known as lidocaine are sometimes used for the management of PHN. In addition, in January 2011, the FDA approved aonce-daily formulation of gabapentin (known as Gralise from Depomed and its partner for pain indications, Abbott) for the treatment of PHN.
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