[資料]製薬各社製品売上(世界)
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。 ●為替レート 為替レート一覧[Infoseek] [02.1.15]$[USD]=\131.16, Euro[EUR]=\116.98, ￡[GBP]=\189.89, SFr[CHF]=\79.088, DKK=\15.73 [02.12.25]$[USD]=\120.45, Euro[EUR]=\124.10, ￡[GBP]=\191.97, SFr[CHF]=\85.52 , DKK=\16.71 [04.01.18]$[USD]=\106.57, Euro[EUR]=\131.83, ￡[GBP]=\191.56, SFr[CHF]=\84.12 , DKK=\17.79 [05.01.05]$[USD]=\104.14, Euro[EUR]=\138.08, ￡[GBP]=\196.07, SFr[CHF]=\89.09 , DKK=\18.58,豪$=79.62,カナダ$=84.96,NZ$=72.73 [06.02.01]$[USD]=\118.00, Euro[EUR]=\142.40, ￡[GBP]=\209.40, SFr[CHF]=\91.51 , 豪$=88.85,カナダ$=103.37,NZ$=80.65 [07.01.01]$[USD]=\117.91, Euro[EUR]=\139.53, ￡[GBP]=\203.26, SFr[CHF]=\? ,豪$=86.48,カナダ$=100.47,NZ$=79.40 [07.02.01]$[USD]=\121.96, Euro[EUR]=\158.99, ￡[GBP]=\241.55, SFr[CHF]=\98.060,豪$=95.76,カナダ$=104.48,NZ$=? [08.01.04]$[USD]=\110.28, Euro[EUR]=\162.60, ￡[GBP]=\219.47, SFr[CHF]=\99.25,豪$=98.23,カナダ$=111.88,韓国100W=11.90(),DKK=21.53 ,NZ$=83.20 [09.01.01]$[USD]=\90.25, Euro[EUR]=\127.02, ￡[GBP]=\130.08, SFr[CHF]=\85.19,豪$=62.38,カナダ$=74.05,韓国100W=6.38(),DKK=15.54 ,NZ$=52.13, 中国元=12.99, ロシアルーブル=2.70 [10.01.04]$[USD]=\93.33, Euro[EUR]=\134.32, ￡[GBP]=\153.92, SFr[CHF]=\90.50,豪$=85.40,カナダ$=90.15,韓国100W=8.20(),DKK=18.15 ,NZ$=69.01, ロシアルーブル=3.32 [11.01.04]$[USD]=\82.78, Euro[EUR]=\110.57, ￡[GBP]=\130.55, SFr[CHF]=\88.40,豪$=85.40,カナダ$=83.93,韓国100W=7.49(),DKK=14.93 ,NZ$=65.22, ロシアルーブル=2.94 [11.12.30]$[USD]=\78.74, Euro[EUR]=\102.21, ￡[GBP]=\123.81, SFr[CHF]=\83.59,豪$=81.12,カナダ$=77.82,韓国100W=6.95(),DKK=13.85 ,NZ$=62.15, ロシアルーブル=2.68,CNY (中国元)=12.71 * 日経ネット：マネー＆マーケット：外国為替クロスレート[] * 為替レート過去データ[] * 外国為替相場過去履歴[] ●製薬企業ニュースサイト Business.com :Pharmaceuticals - Web Sites --- 収録項目profile | financials | competitors | people --- 収録項目AstraZeneca| Aventis| Bayer AG| Bristol-Myers Squibb| Eli Lilly GlaxoSmithKline| Johnson & Johnson| Merck & Co| Novartis AG| Novo-Nordisk A/S Pfizer| Roche Holding Ag| Schering-Plough Hoovers Online PR Newswire : Company News Archive: Health/Biotech |Annual Report ●医薬品市場ニュースサイト ★IMS Health News Release [] [] [] ■個別製薬会社
●企業情報 ●金融庁電子開示システム（EDINET) - 有価証券報告書 - 金融庁は「証券取引法に基づく有価証券報告書等の開示書類に関する電子開示システム」 (説明)の試験運用期間を終了し、 平成16年6月以降、開示書類等の電子化が原則義務化（EDINETへ移行） （Electronic Disclosure for Investors' NETwork） つまり株式公開を行う企業に提出を義務づけられている「有価証券報告書」などは、 ネット公開されることになる。 ●米国証券公正取引委員会[SEC] Filings検索 from 米国証券公正取引委員会[SEC][Securities and Exchange Commission] -SEC Filings & Forms (EDGAR) - Companies for SIC 2834 - Pharmaceutical Preparations[549社] - 企業名などで検索し、開くと当該企業のドキュメントが大量に出てくるが 「有価証券報告書」を見たい場合、Annual Reports Form 10-K EDGARR is... the SEC's Electronic Data Gathering, Analysis and Retrieval system 民間検索サイト★SEC Info[Fran Finnegan & Company]も便利 ●参考 Biotech's old soldiers[Pharmalicensing.com] (15 November 2005) -最近の合併動向 【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] 2009.9.3 大日本製薬かSepracor社を買収(総額U.S. $2.6 Billion) - [日本語] - [説明資料]
■Abbott
【米アボット】ソルベイの製薬部門買収‐新興国市場のインフラ獲得へ[2009.9.30] 【データモニター】ソルベイ買収でアボットの成長率は大幅改善[2009.10.9] ●決算 [各12月末]●売上
($ milllion) 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 備考 純売上高 30,764.7
旧25,527.625,914.2 22,476.3 22,337.8(+13.5) 19,680.0(+13.9) 17,280.3 17,684.7(+8.6) 16,285.2(+18.5) 13,745.9 営業利益 6,235.7 5,693.8 4,578.5 2,042.2 4,362.3 3,898.3(+31.1) 2,974.0 3,530.1 1,894.0 3,400.6 経常利益 7,193.8 5,856.3 4,469.6 2,276.4 4,619.9 4,125.6(+21.8) 3,387.2 3,673.4 1,883.1 3,816.4 純利益 5,745.8 4,880.7 3,606.3 1,716.8 3,372.1 3,235.9(+17.5) 2,753.2 2,793.7 1,550.4 2,786.0 研究開発費 2,743.7 2,688.8 2,505.6 2,255.2 1,821.2 1,696.8(+4.5) 1,623.8 1,561.8 1,577.6 1,351.0 取得研究開発費 170.0 97.3 - 2,014.0 17.1 279.0 100.2 従業員数 73,000 69,000 68,000 66,663 59,735 ? 72,181 71,819 71,426 60,571 ■セグメント別売上高 ●Pharmaceutical (a) 16,486(-1.3) 16,708(+14.2) 14,632(+18.0) 12,395(-9.5) 13,691
旧8,138(+16.1)11,913
旧7,0106,051 4,268 3,759 米国内医薬品 国内売上高 7,794(-8.3) 8,497(+8.9) 7,806(+19.2) 6,550(-19.5) 国際売上高 8,692(+5.8) 8,211(+20.3) 6,826(+16.8) 5,845(+5.3) ●Diagnostic (b) 3,578(+0.1) 3,575(+13.2) 3,158(+11.1) 3,979(+5.9) 3,756(+11.2) 3,378 3,040 2,897 2,929 国内売上高 939(+4.4) 899(+9.6) 820(+2.6) 1,356(+7.5) 1,252(+11.8) 国際売上高 2,639(-1.4) 2,676(+14.5) 2,338(+14.4) 2,633(+5.1) 2,504(+10.9) ●Nutritional 5,284(+7.3) 4,924(+12.2) 4,388(+1.7) 4,313(+9.6) 国内売上高(Ross) 2,636(+6.3) 2,479(+5.6) 2,348(-9.4) 2,629(+4.2) 国際売上高 2,648(+8.3) 2,445(+19.8) 2,040(+14.4) 1,684(+19.1) ●Vascular 2,692(+20.1) 2,241(+34.7) 1,663(+53.8) 1,082(+327.7) 国内売上高 1,599(+32.7) 1,205(+39.6) 863(+33.5) 647(+359.2) 国際売上高 1,093(+5.5) 1,036(+29.4) 800(+83.9) 435(+288.0) ★Ross - - - - 2,523(+8.5) 2,326 2,136 2,088 2,088 ★International (a)(b) - - - - 6,967(+13.0) 6,166 5,321 5,036 4,418 国際医薬品 - - - - 5,164(+12.8) 国際栄養剤 - - - - 1,803(+13.7) ★Total Reportable Segments 27,448 23,841 21,769 21,637 19,101 16,548 17,268 15,972 Other 2,725(+31.1) 2,080 2,073(+12.5) 707 701 579 732 417 313 ■Net Sales 30,765(+4.2) 29,528(+13.9) 25,914(+15.3) 22,476(+0.6) 22,338(+13.5) 19,680 17,280 17,685 16,285 国内売上高 14,220(+0.4) 14,170(+10.1) 12,874(+12.0) 11,534(-7.5) 12,442(+13.0) 国際売上高 16,545(+7.7) 15,358(+17.8) 13,040(+18.8) 10,942(+10.9) 9,896(+14.2) TAP Pharmaceutical 3,260(-3.0) Hospital* - - - - - - 3,078 2,979 2,778 ■国別売上高 United States 14,453 14,,495 13,252 11,995 12,707 11,242 9,919 10,998 10,249 Japan 1,590 1,249 1,111 1,054 1,027 987 897 784 748 Germany 1,481 1,381 1,235 885 992 811 785 721 644 The Netherlands 1,801 1,,753 1,271 1,061 899 705 556 446 349 Italy 1,172 1,089 974 848 806 745 658 572 496 Canada 902 924 832 762 680 595 526 512 468 France 959 977 854 696 657 587 467 Spain 970 909 731 583 542 513 426 United Kingdom 779 725 627 517 504 496 397 その他 6,658 6,026 5,027 4,075 3,524 2,999 2,649 3,652 3,331 Consolidated 30,765 29,,528 25,914 22,476 22,338 19,680 17,280 17,685 16,285 from- ABBOTT REPORTS 15.5 PERCENT SALES INCREASE IN THE FOURTH QUARTER; 13.9 PERCENT INCREASE FOR 2004[2005.1.18] from - Abbott Reports 14.3 Percent Sales Increase in the Fourth Quarter; 11.3 Percent Increase for 2003[2004.1.16] ●Kos Pharmaceuticals, Inc 2006.11.5 Abbottと合併契約締結。
($ milllion) 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 備考 ★Pharmaceutical Humira 5,488(+21.4) 4,521(+47.6) 3,064(+49.9) 2,064 1,400 852 280 - - - [adalimumab]リウマチ 米国 2,519(+11.7) 2,255(+36.6) 1,651(+40.4) 1,176(+38.4) 849(+53.2) 555(+125.6) 246(-) 海外 2,969(+31.0) 2,266(+60.4) 1,413(+62.9) 868(+57.6) 551(+85.4) 297(-) 34(-) Mobic 米国のみ - - - 1232(+107.8) 593(+85.1) 320(+40.0) 229(40.1) 163(-) - [Meloxicam]消炎鎮痛 Depakote 425(-68.8) 1,364(-13.4) 1,575(+20.4) 1,308 1,096 1,027 927 898 869(+12.0) 39(+1.9) [divalproex sodium]抗てんかん剤 米国 331(-73.8) 1,262(-14.8) 1,480(+20.3) 1,230(+18.5) 1,037(+6.1) 978(+10.4) 886(+2.9) 861(-0.9) 海外 94(-7.5) 102(+7.4) 95(+21.7) 78(+24.8) 59(+20.3) 49(+18.2) 41(+12.3) 37(-3.6) Clarithromycin 651(-10.1) 724(-11.2) 816 1,065 1,183 1,221 1,102 537(-7.2) 622(-6.3) [Biaxin,Biaxin XL, Klacid, Klaricid]抗生物質 米国 - 14(-) 36(-75.9) 151(-50.5) 306(-33.2) 458(-15.0) 538(+10.5) 487(-9.2) 海外 - 637(-7.4) 688(+3.5) 665(-12.5) 759(+4.8) 725(+6.1) 683(+11.0) 615(-1.0) Kaletra 1,366(-7.3) 1,474(+11.2) 1,325(+16.7) 1,135 1,005 896 752 551 210(-) 83(-) [lopinavir/ritonavir]HIV 米国 446(-12.9) 513(-4.7) 538(+5.0) 512(+22.0) 420(+5.5) 398(+3.9) 383(+20.6) 318(51.3) 海外 920(-4.3) 961(+22.1) 787(+26.3) 623(+6.5) 585(+17.6) 498(+35.0) 369(+58.5) 233(179.4) TriCor/Trilipix 米国のみ 1,337(-0.3) 1,341(+10.1) 1,218(+16.2) 1,048(+13.1) 927(+18.9) 779(+37.6) 566(+40.6) 403(52.9) 264(+74.1) - [fenofibrate]高脂血症 Ultane/Sevorane - 787(+3.7) 759(-5.0) 799 874 774 674 567 192(+9.8) 309(+10.9) [Sevoflurane]全身麻酔剤 米国 - 193(-3.4) 200(-23.4) 260(-22.5) 336(+16.0) 290(+12.7) 257(+16.3) 221(15.0) 海外 - 594(+6.2) 559(+3.9) 539(+0.2) 538(+11.1) 484(+15.9) 417(+20.6) 346(11.9) Niaspan[米国] 855(+8.8) 786(+19.4) 658(-) - - [Niacin]脂質低下剤;2006Q4 Kos Pharmaceuticals Inc買収に伴う Synthroid 502(-4.3) 524(-1.6) 533(-0.3) 534 554 689 609 520 445(-) 22(-) [levothyroxine sodium]甲状腺 米国 415(-4.5) 435(-5.0) 458(-2.7) 470(-5.7) 498(-21.7) 637(+12.8) 565(+15.5) 489(+9.9) 海外 97(-3.1) 89(+19.2) 75(+17.2) 64(+14.5) 56(+7.8) 52(+16.6) 44(+42.9) 31(+42.9) Omnicef 米国のみ - - 235 637(+28.6) 495(+53.6) 323(+30.5) 247(+58.0) 157(74.7) 90(109.2) - [cefdinir]2007ジェネリック競合 Leuprolide 海外のみ 800(+22.8) 651 - 230(+4.6) 219(+11.0) 198(+8.2) 183(+6.3) 105(13.6) 163(+6.2) [Lupron,Lucrin] 米国 540(+43.2) 377 海外 260(-5.3) 274 Lansoprazole 海外のみ 651(-) - 173(+12.3) 154(+8.0) 142(+7.8) 132(+25.4) 172(5.6) 93(+18.0) [Prevacid,Ogastro] 米国 377(-) 海外 274(+6.5) Flomax - - - (B-Iとの併販解消04.8) 724 575 [tamsulosin HCl] 米国 - - - - - 689(+24.7) 553(34.6) 411(+47.7) 海外 - - - - - 35(+54.9) 22(+44.2) 16(+60.0) Meridia/Reductil - - - - - - 272 [sibutramine] 米国 - - - - - - 75(-10.7) 84(-) 海外 - - - - - - 197(61.8) 118(-) ★Medical Products Group Pediatric Nutr. 2,849(+7.8) 2,642(+13.6) 2,326(+14.8) 2,026 1,795 1,741 1,620 1,490 [] 米国 1,306(+3.0) 1,268(+2.8) 1,233(+9.4) 1,128(+2.7) 1097(-4.3) 1146(+4.8) 1093(+9.0) 1004(-3.6) 1041(-0.1) 海外 1,543(+12.3) 1,374(+25.7) 1,093(+21.6) 898(+28.7) 698(+17.3) 595(+13.0) 527(+8.4) 486(1.1) 480(+8.5) Adult Nutritionals 2,375(+6.4) 2,232(+10.3) 2,024(+7.6) 1,882 1,792 1,597 1,400 1,366 [] 米国 1,269(+9.2) 1,162(+7.8) 1,077(+1.9) 1,097(+1.9) 1050(+12.4) 934(+15.5) 809(-3.5) 838(0.7) 833(+3.8) 海外 1,106(+3.3) 1,070(+13.0) 947(+14.9) 785(+9.7) 742(+11.5) 663(+12.1) 591(+11.9) 528(3.9) 508(+0.2) Diabetes Care 1,242(-8.2) 1,353(+8.4) 1,249(+9.9) 1,136 1,067 791(+46.1) 541 494 [] 米国 498(-11.0) 559(+1.1) 553(+1.3) 547(+4.8) 522(+38.1) 378(+84.8) 204(-0.4) 205(8.1) 190(+0.5) 海外 744(-6.3) 794(+14.2) 696(+18.0) 589(+8.2) 545(+31.8) 413(+22.7) 337(+16.8) 289(8.8) 265(+7.8) Coronary Stents 1,618(+35.0) 1,199(+78.4) 672(-) - 米国 1,029(+53.8) 669(+118.5) 306(-) - 海外 589(+11.3) 530(+44.8) 366(-) - Core Laboratory Diagnostics 3,027(-2.3) 米国 605(-1.9) 海外 2,422(-2.4) Medical Optics 890(-) - 米国 337(-) - 海外 553(-) - Molecular Diagnostics 316(+18.3) 米国 150(+23.5) 海外 166(+14.0) Other Coronary - 642(+6.5) 604(+32.5) 米国 - 298(-0.5) 300(+13.0) 海外 - 344(+13.4) 304(+59.8) Endovascular - 400(+3.1) 388(+11.9) 米国 - 238(-7.6) 257(+0.8) 海外 - 162(+24.1) 130(+42.9) Vascular Devices - - - - 253 221(+19.3) 185(+44.7) 205(33.3) - [] 米国 - - - - 141(+11.7) 221(+19.3) 185(+44.7) 205(33.3) - 海外 - - - - 112(+18.8) - - - - ★TAP Pharm (非連結) Prevacid 米国のみ - [1-4月]649 2,275 2,600(+4.0) 2,501 2,592(-18.7) 3,190(+1.0) 3,157(7.0) 2,951(+7.7) 2,739 [Lansoprazole]潰瘍 Lupron 米国のみ - [1-4月]182 645 662(-5.2) 699 770(-2.2) 788(-10.1) 876(5.2) 833(+4.2) 799 [Leuprolide]前立腺癌 Teveten(R) (eprosartan mesylate) and Teveten HCT (eprosartan mesylate/hydrochlorothiazide) Cardizem(R) LA (diltiazem hydrochloride) の米国販売権をKos Life Sciences(KLS; Kos子会社)が Biovail Corporation から獲得。2005.5.2に契約し2005.5から承継。 ★Niaspan Kos が1997.9米国販売開始。 欧州ではKosのパートナーとしてMerck KGaAが2003.11.3にNiaspan英国発売、2004.1 １３の欧州諸国の承認取得。 Kosは2003.11.4 Niaspan and Advicorの米国の共同販売契約を 武田薬品と契約。 Kosは2003.8.20 Niaspan and Advicorのカナダの共同販売契約をOryx Pharmaceuticals, Incと契約し、 Oryxは2003.12に承認申請。 ★Advicor [niacin+losvastatin] FDA承認2001.12.17 by Kos、米国発売2002.1.28 Kosは2003.11.4 Niaspan and Advicorの米国の共同販売契約を 武田薬品と契約。 Kosは2003.8.20 Niaspan and Advicorのカナダの共同販売契約をOryx Pharmaceuticals, Incと契約し、 Oryxは2003.12に承認申請。
($million) 2006Q1+Q2 2005 2004 2003 2002 2001 2000 1999 備考 売上高 170.8+223.7 746.197 495.545 293.907 172.693 91.447 60.174 36.340 [] Advicor 142.6 w/+34.9 116.0 108.2 67.4 27.1 [niacin+losvastatin] Niaspan +131.0 435.2 319.1 226.5 145.6 [niacin] Azmacort 22.9+26.5 103.2 68.3 - []2004.3.8 Aventisから世界独占権獲得 Teveten,HCT +5.5
31.6 w/+31.3 w/22.1 - - [eprosartan]販売開始2005.5;from Bioval Cardizem LA +25.8 69.7 - - [diltiazem]販売開始2005.5;from Bioval []
●Abbott ●Press release Abbott Reports Double-Digit Sales and Ongoing Earnings Growth in Fourth Quarter; Issues Ongoing Earnings Outlook for 2011[2011.1.26] Abbott Reports Double-Digit Sales and Earnings Growth in Fourth Quarter; Issues Strong Earnings Outlook for 2010[2010.1.27] Abbott Reports Double-Digit Sales and Earnings Growth in Fourth Quarter; Issues Strong Earnings Outlook for 2010[2009.1.27] Abbott Reports 16.1 Percent Sales Growth in Fourth Quarter[2008.1.23] ●Products ■Investor Relations ●SEC Filings 10-K[2011.2.18] - [pdf] - [doc] 10-K[2010.2.19] - [pdf,252p] - [doc] - [xls] 10-K[2009.2.20] - [pdf,318p] - [doc] - [xls] 10-K[2008.2.19] - [pdf,137p] 10-K[2007.2.23] - [pdf,250] 10-K[2006.2.22] - [pdf] - [xls] 10-K[02/25/04] ●IR Fact Book ●Annual Report ---Annual Report には製品個別やOperation reviewはあるが売り上げのデータ記載なし - Abbott Reports Strong Fourth-Quarter Results and Record Operating Cash Flow in 2006 [2007.1.24] - 2006 Annual Report - [pdf] - Abbott Reports Record Sales, Earnings and Cash Flow in 2005[2006.1.25] ★疾病サイト Pediatric Health Men's Health Women's Health Diabetes HIV Horizon Respiratory Infections Pain Management Animal Health ●Abbott Lab Online - http://www.rxabbott.com/
●アボット ジャパン - http://www.abbott.co.jp 2003年２月１日、ダイナボット(株)と北陸製薬(株)が合併し、アボット ジャパン(株)設立 アボット ジャパン株式会社（ダイナボット（株）と北陸製薬（株）が合併） 米国アボット、ソルベイ製薬の買収を完了[2010.2.17] ソルベイ製薬（株） 社名変更のお知らせ[2010.4.12] アボット ジャパン、アボット製薬合併を完了[2011.4.1] - 合併完了に伴い、アボット製薬の業務拠点を廃止し、アボット ジャパンに移転。 またアボット製薬の製品、業務はすべてアボット ジャパンに承継されます。 ●医療関係者の皆様 ★医療用医薬品 ★血糖測定器 ●プレスリリース アボット ジャパン(株)、4月から医療用医薬品の自社販売を開始[2006.3.31] - 1953年、アボット（米国）の子会社であるアボットジャパン （旧ダイナボット(株 )）と大日本住友製薬株式会社（旧大日本製薬(株)）との間で、アボット製品の国内にお ける総代理店契約が締結され、旧大日本製薬がアボット製品の販売を始めました。 両社 の販売提携契約は、2006年3月31日をもって契約期間満了により終結いたします。 アボット ジャパン(株)と大日本住友製薬(株)販売提携契約を満了[2006.3.27]
●Tap Pharmaceutical Products Inc.[US] - http://www.tap.com/ 1977年Abbott Laboratoriesと武田薬品工業の合弁会社として設立。 2008.5.1 武田薬品と米Abbottは合弁事業TAPを終了。 2008.7.1 Takeda Pharmaceuticals North America, Inc.[TPNA]及びTakeda Global Research & Development Center, Inc[TGRD]がTap Pharmaceutical Products Inc.と合併 従業員数3,000人(2006末)、年間売上(2006) $3,362 Million ●Products Prevacid ●Prescribing Information ●Diseases & Conditions
($ 000) 2008/1-4 2007 2006 2005 2004 2003 2002 2001 備考 売上高 853,093 3,001,738 3,362,672 3,259,850 3,361,634 4,034,000 販売原価 228,747 719,976 835,834 883,404 990,417 粗利益 2,526,838 2,376,446 2,371,217 営業利益 355,861 1,560,620 1,512,326 1,373,993 1,176,389 経常利益 356,101 1,564,488 1,523,326 1,379,331 1,181,052 当期純利益 237,994 996,030 951,621 882,772 749,969 研究開発費 54,381 161,013 245,476 219,412 167,625 従業員数[連結] 2,900 3,000 3,475 Prevacid米国 649,303 2,275,293 2,599,886 2,501,052 [Lansoprazole]潰瘍 Lupron米国 182,042 645,450 662,374 698,806 [Leuprolide]前立腺癌
■Abiogen Pharma S.p.A[伊]
- http://www.abiogen.it/english/home.asp 1997年 創立 Istituto Gentili S.p.Aが米メルク社による買収時、同社創立者の孫がスピンアウト ●会社決算(2007 売上金額比) 骨粗鬆症・NSAIDS 47.75% 呼吸器系 12.66% 糖尿病 18.63% 皮膚科疾患 9.23% その他 11.73%
(Eur 000) 2007 2006 2005 2004 2003 2002 2001 売上高 65,364 72,190.58 69,130.31 69,410.20 内Pharma 47,820[73.15%] 57,136.18 53,996.36 49,290.60 42,200 36,300 34,400 Manufacturing 12,880[19.72%] 11,846.84 12,277.79 15,207.90 12,600 10,700 10,700 Royalty&Down payment 4,660[7.13%] 3,207.56 1,856.16 4,911.70 12,000 7,600 13,950 EBITDA 7,640 8,961 EBIT 2,687.28 2,814.94 2,672.57 純利益 (639.24) (1,017.69) (478.72) 従業員数[連結] 369
●Abiogen Pharma S.p.A[伊] ■Pharma ●Abiogen Pharma's products Nerixia (neridronic acid sodium) ■R & D ●Licensing In
●Licensing Out
製品名 薬効 ライセンス先 備考 alendronate(Alendros) 骨粗鬆症 米Merck & Co Lyophilised bacterial lysates(Broncho Munal) 瑞O.M. Calcium dobesilate(Doxium/Doxiproct Plus) 瑞O.M. E.Coli Bacteria exts(Uro Munal) 瑞O.M. diacerein(Fisiodar) 瑞Tran Bussan aceclofenac(Gladio) NSAIDs 西Almirall Prodesfarma tecalcitol(Vellutan) 帝人 octopirox/sebomina/Norgel(Kourilles) 伊Farmaka clotiazepam(Tienor) 伊Farmaka lyophilised collagene(Condress) 伊Euroresearch xibornol(Bornilene) 伊Euphar clarithromycin(Soriclar) マクロライド抗生物質 伊Abbott ●Pipeline /2008.8.3
製品名 薬効 ライセンス先 地域 clodronate 骨粗鬆症 伊SPA、伊Fidia 伊e 英Beacon Pharmaceuticals 欧州 ギリシャ・キプロス・トルコSamaritan Pharmaceuticals 欧州 加Oryx Pharmaceuticals In カナダ E Vitamin 400 IU 伊Bracco 伊 glibenclamide+metformin 糖尿病 伊Fornier Pharma/Solvay Pharma 伊 仏Merck Sante 欧州 米BMS 米国 メキシコProductos Roche メキシコ tacalcitol 伊IDI Farmaceutici 伊 17β-estradiol 伊Solvay Pharma 伊 ■Manufacturing 受託加工など ■プレスリリース(の代わり) Abiogen Pharma starts a clinical phase II in Panic Disorders (21st May 2008)
製品名 成分 薬効 段階 備考 CL-I.A. clodronate 変形性関節症 P3 Nerixia neridronate 骨粗鬆症・Algodistrophy P3 BTG1640 isoxazoline誘導体 不安症・パニック障害 P2 TALL 104 Human cytotoxic cell line 癌 P1 Combotox MOAB-Anti-CD19 Toxin
MOAB-Anti-CD22 Toxin非ホジキンリンパ腫 P1 IMTOX 22 MOAB-Anti-CD22 Toxin 非ホジキンリンパ腫 P1
- ABIO 08/01のパニック障害P2試験を開始。
Abiogen starts a Phase II in cancer with its new cell-therapy.(20th Nov 2006)
- ABIO 05/01 のP2試験実施を承認された。 本剤は異種細胞療法剤で慢性骨髄性白血病などに有効とされる。
Abiogen Pharma's new anti-anxiety drug starts a clinical phase II in Generalized Anxiety Disorders in Vienna.(1st Jul 2006)
- ABIO 08/01のGADのP2試験を開始。
Abiogen Pharma / Oryx Pharmaceutical: a license agreement for Disodium Clodronate(20th Jun 2005)
-
Abiogen Pharma's new cell therapy starts a clinical phase I-II in Peritoneal Carcinosis(14th Apr 2005)
-
A NEW VAGINAL AND SURGERY DOUCHE(6th Apr 2004)
-
EMEA grants to Abiogen Pharma the Orphan Drug status for a new compound in myelofibosis indication.(8th Oct 2003)
- OGP (10-14)L (H-Tyrosine-Glycine- Phenilalanine-Glycine-Glycine-OH) のオーファン申請をEMEAは2003.9.10に承認した。 適応はchronic idiopathic myelofibrosis (CIMF)慢性原発性骨髄線維症.
Abiogen Pharma Spa: authorized Phase I for an OGP drug(5th Dec 2002)
-
Clodronate for the treatment of Osteoarthritis: positive results for Abiogen Pharma.(2nd Oct 2002)
-
New trends in the research of new vaccines for Hepatitis C and Tetanus on a biotechnological basis in Italy.(26th Jun 2002)
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The first drug Worldwide for Osteogenesis Imperfecta, the "illness of bones of crystal", developed and registered in Italy.(25th Jun 2002)
- 世界初の骨形成不全治療薬Neridronateが承認された。 骨折と苦痛をドラスチックに軽減。
■Abraxis BioScience Inc.
- http://www.abraxisbio.com/; (Nasdaq: ABII) 本社Los Angeles, California 2005.11.27 ABIとAPPの合併交渉に入り、2006.4.18に合併完了、Abraxis BioScience, Inc. (Abraxis)となった。 。 2007.7.2 Abraxis BioScience (Nasdaq: ABBI)は、病院向け医薬品中心にAbraxis Pharmaceutical Products(APP)を分離。 2007.11.13 残ったABBIはAbraxis Oncology and Abraxis Research事業を含み ;→APP Pharmaceuticals Inc[APPX→APCVZ]に社名変更。 2008.7.6 APP Pharmaceuticals, IncはFresenius SEに買収完了[09.10.9] NASDAQ=APCVZ 2009.1 新設子会社Abraxis Health Incをスピンオフ ●旧American BioScience, Inc.[ABI,ABS] 1994.6 設立。; Santa Monica, CA ; 非上場 旧社名 VivoRx Pharmaceuticals, Inc 因みに健康食品・一般薬販売のAmerican BioScience, Inc. - http://www.americanbiosciences.com/ は別の企業。 アステラス製薬が一部資本参加しており、日本での拒否権を保有。[1998.6.9] ●旧American Pharmaceutical Partners, Inc. (APP) - http://www.appdrugs.com/; American BioScience, Inc.の子会社(67.9%)。 抗ガン剤と抗感染薬の注射剤に重点。 NASDAQ: APPX 1996 ジェネリック医薬事業開始 1998.6 Fujisawa USA,Inc.のジェネリック注射薬事業を買収。 We are a Delaware corporation that was formed in 2001 as successor to a California corporation formed in 1996. 2003後期 Abraxis Oncology division 設立 2005.12末 American BioScience, Inc.は当社株式の66.2%を保有。 2005.11.27 ABIとAPPの合併交渉に入り、2006.4.18に合併完了、Abraxis BioScience, Inc. (Abraxis)となった。 。 Abraxis BioScience, Inc. (Abraxis) -http://www.abraxisbio.com/index.htm At June 30, 2006, we had the following wholly owned subsidiaries, Pharmaceutical Partners of Canada, In c., Pharmacetical Partners Switzerland, GmbH, Puerto Rico, LLP, VivoRx AutoImmune, Inc., Chicago BioSci ence, LLC and Transplant Research Institute our majority owned subsidiary, Resuscitation Technologies, LLC and our investment in Drug Source Company, LLC, which is accounted for using the equity method ●会社決算*2003-2006の旧データは2007.7.2 Abraxis BioScience (Nasdaq: ABBI)は、病院向け医薬 品中心にAbraxis Pharmaceutical Products(APP)の分離以前のデータ。 ●事業別売上高
($000) 2008 2007 2006 2005 2004 2003 2002 2001 2000 売上高 345,309 333,686
旧647,674182,287
旧583,201
旧765,488(+47)135,,675
旧385,082
旧520,757(+29)237
旧405,010
旧405,247351,315
旧351,744283,616 192,029 165,495 粗利益 306,241 299,236
旧315,328161,104
旧295,122
旧457,976111,609
旧181,646
旧293,522(103)
旧213,236
旧212,993189,742
旧190,052141,778 70,410 59,908 営業利益 (292,332) (54,356)
旧160,160(146,173)
旧140,797
旧3,756(5,908)
旧86,270
旧87,328(74,271)
旧136,819
旧64,949120,621
旧87,92150,589 25,382 -12,246 経常利益 (278,709) (49,556)
旧137,180(150,515)
旧123,785
旧(17,598)(12,184)
旧60,865
旧55,646(76,301)
旧120,466
旧46,566101,539
旧67,26135,578 22,167 (13,797) 純利益 (276,771) (41,604)
旧34,358(124,551)
旧(46,897)(12,662)
旧17,657(76,301)
旧18,22126,353 18,647 12,628 -8,759 研究開発費 103,590 88,717
旧46,49763,073
旧27,787
旧96,89150,121
旧18,454
旧68,89634,896
旧16,707
旧51,46217,422
旧39,26935,344 13,790 13,016 取得研究開発費 13,900 - 83,447 - - 従業員数 734 1,375 1,864 1,488 1,381 研究開発 310 72 240 92 73(Ph.D.=35) 品質管理 315 376 282 301 製造部門 160 779 807 798 711 販売営業 136 61 247 207 175 事務管理 128 148 194 109 121 [ABRAXANE] 2001.11 旧American BioScience[ABI]から北米の販売権、全世界製造権を取得契約。 - 2004年米国paclitaxel市場規模は１億ドル(IMS) 2005.1.7 FDA承認、米国発売は2005.2.7。 2005.5.27 日本に関して大鵬薬品にライセンス 2006.4.26 AstraZenecaと米国で共同販売。 因みにAbraxis Oncology(従業員280人、うちMR 169人) Taiho Pharmaceutical Co., Ltd.: On May 27, 2005, we entered into a license agreement with Taiho Pharmaceutical Co., Ltd. under which we granted to Taiho the exclusive rights to market and sell Abraxane(R) in Japan. We, along with Taiho, established a joint steering committee to oversee the development of AbraxaneR in Japan for the treatment of breast, lung and gastric cancer and other solid tumors. Under this license agreement, Taiho paid us a non-refundable, upfront payment and will make additional payments to us upon achievement of various clinical, regulatory and sales milestones, with total potential payments in excess of $50.0 million. In addition, we will receive royalties from Taiho based on net sales under the license agreement.
($000) 2008 2007 2006 2005 2004 2003 2002 備考 Critical care - 382,772 302,244
旧303,485(+86)163,581(-8) 178,242(+5) 169,849(+25) 135,370 oxytocin,heparin Anti-infective - 193,704 213,489(+26) 169,818(+36) 125,052(+31) 95,581(+29) 74,082 Oncology - 55,308 57,872
旧57,983(+14)51,084(-47) 95,866(+18) 81,049(+32) 61,204 受託製造他 - 15,590 9,595
旧9,485(-)599(-90) 5,850(+21) 4,836(-29) 6,818 純売上高 - 647,374 583,201
旧584,442(+52)385,082(-5) 405,010(+15) 351,315(+27) 277,474 Abraxane 335,631 324,692 174,906(+31) 133,731(-) - - - [Paclitaxel-albumin]乳癌;米国発売2005.2.7 Research Revenue 9,678 8,994 7,381
旧6,140(+216)1,944(+720) 237 総収入 345,309 333,686
旧647,374182,287
旧765,488(+47)135,675
旧520,757(+29)237
旧405,247351,744 283,616 [Competition 2006]
We believe that Abraxane(R) competes, directly or indirectly, with the primary taxanes in the market place, including Bristol-Myers Squibb's Taxol(R) and its generic equivalents, Sanofi-Aventis' Taxotere(R) and other cancer therapies. Many pharmaceutical companies have developed and are marketing, or are developing, alternative formulations of paclitaxel and other cancer therapies that may compete directly or indirectly with Abraxane(R).
●Abraxis BioScience Inc. ●Products ★Abraxane ★Product Catalog ●Research ★NDA pipeline ●IR/Media ★Press Releases Abraxis BioScience Reports 2008 Fourth Quarter and Full-Year Financial Results[2009.3.3] Abraxis BioScience Reports Record Revenue of $765 Million in 2006 Versus $521 Million for 2005[2007.2.26] American BioScience Licenses ABRAXANE(TM) to Taiho Pharmaceutical Co., Ltd., One of the Largest Oncology Companies in Japan[2005.11.15] ★SEC Filings 10-K Annual report[2009.3.6] - [pdf,119P] - [doc] - [xls] 10-K Annual report[2008.3.17] - [pdf,528p] - [doc] - [xls] 10-K Annual report[2007.3.1] - [pdf] 10-K Annual report[2006.3.10] - [pdf]
■ACADIA Pharmaceuticals Inc[US]
- 1997.1創立; (Nasdaq: ACAD); 創薬技術を用い、神経系医薬開発を行うバイオ企業。 Our headquarters and biology research facilities are located in San Diego, Calif ornia, and our chemistry research facility is located in Malmo, Sweden 従業員数=101 (2004.12末)うち研究開発87人。 ■会社決算 (12月末) ($000) 2004 2003 2002 2001 2000 収入 提携等による 4,529 4,953 3,655 3,714 4,193 他の研究収入 75 2,425 2,621 - 119 計 4,604 7,378 6,276 3,714 4,312 営業支出 研究開発 23,454 16,935 14,921 13,090 9,728 一般管理費 4,889 2,791 2,818 3,756 2,999 株式償還 2,356 1,392 1,163 2,147 2,854 計 30,699 21,118 18,902 18,993 15,581 営業損失 (26,095) (13,740) (12,626) (15,279) (11,269) 受入利息 607 360 420 1,494 1,516 支払利息 (429) (712) (662) (621) (441) 純損失 (25,917) (14,092) (12,868) (14,406) (10,194) ●開発段階の医薬 ACP-103 P2 パーキンソン病治療薬による精神症状の治療 ACP-103 P2 統合失調症の併用療法 ACP-104 P2 統合失調症の治療; N-Desmethylclozapine *既知物質のため物資特許の対象とはならないので、用途特許を申請中。 AGN-XX & AGN-YY P1 神経因性疼痛 AC-262271 前臨床 緑内障 ●提携 [Allergan] 2003.3 眼科用新薬開発で３年間契約 $3.9 million(2004) and $2.7 million(2003)受領 当初1997.9 神経因性疼痛及び眼科用薬の新薬創製で提携契約。 1999.7 緑内障治療薬開発で提携。 [The Stanley Medical Research Institute, or SMRI] 2004.5 ３年契約 統合失調症の新薬開発 [Aventis] 2002.7 [Amgen] 2001.12 small molecule drugs の創薬
●ACADIA Pharmaceuticals Inc ■Investors ●SEC Filings Annual Filings 10-K[2005.3.18] - [pdf][84p] ●Annual Reports ●Press Releases ■News ●Programs ●Technology ●Partnering
■Acorda Therapeutics Inc
- 1995.3 設立。 spinal cord injury (SCI), multiple sclerosis (MS)などの神経分野 2008.2 Neurorecovery, Inc.を買収 ●会社決算■製品＆パイプライン
($ 000) 2009 2008 2007 2006 2005 2004 2003/12 2003/6 2002/6 備考 Zanaflex売上 49,959 47,728 39,426 26,944 4,809 (4,417) - - - [tizanidine HCl]筋弛緩剤;痙性麻痺 License収入 4,714 - - - - Grant収入 - 99 60 407 336 479 382 474 132 収入 合計 54,673 47,827 39,486 27,351 5,145 (3,938) 382 474 132 粗利益 43,284 36,472 31,130 20,228 13 (4,823) 382 474 132 営業利益 (81,257) (73,439) (39,448) (23,467) (34,411) (44,767) (36,773) (25,706) (22,338) 当期純利益 (83,940) (74,340) (37,974) (24,019) (35,531) (44,741) (36,712) (25,734) (21,182) 研究開発費 34,611 36,604 22,410 12,055 12,890 21,999 16,743 17,527 11,147 研究開発関連Party - - - - - - 3,343 2,265 4,687 従業員数[連結] 249 126
●Ampyra[dalfampridine (4-aminopyridine, 4-AP), 旧Fampridine-SR] 多発性硬化症
(Elanから全世界の権利獲得。 米国Acorda、米国外Biogen-IDEC)【2009】
Ampyra was approved by the FDA in January 2010 for the improvement of walking in people with MS. This was demonstrated by an increase in walking speed. To our knowledge, Ampyra is the first and only product indicated to improve walking in people with MS. We intend to commercially launch Ampyra in the U.S. in March 2010, using our own specialty sales force. Under our 2009 Collaboration Agreement, Biogen Idec has the right to develop and commercialize Ampyra in markets outside the U.S. In January 2010, Biogen Idec announced that it submitted an MAA to the EMA and an NDS to Health Canada for Ampyra, known outside the U.S. as fampridine.Ampyra is an oral treatment approved by the FDA on January 22, 2010 as a treatment to improve walking in patients with MS. This was demonstrated by an increase in walking speed. Ampyra demonstrated efficacy in people with all four major types of MS (relapsing remitting, secondary progressive, progressive relapsing and primary progressive). Ampyra can be used alone or with existing MS therapies, including immunomodulator drugs. Ampyra is an extended release tablet formulation of dalfampridine (4-aminopyridine, 4-AP), which was previously referred to as fampridine. We have obtained Orphan Drug designation from the FDA for dalfampridine in MS, which will provide Ampyra with seven years of market exclusivity for this use. We also have patents and pending patent applications covering Ampyra. We plan to file for patent term extension for Ampyra under the Hatch-Waxman law that allows for up to five additional years of patent protection based on the development timeline of a drug. We plan to submit the applications by the deadline of March 22, 2010. Although we plan to apply to extend the two patents that we expect to be listed in the FDA Orange Book (the list of approved drug products and their therapeutic equivalents, if any) for AMPYRA, we will ultimately need to select only one patent for extension, if granted.
Background
MS is a chronic, usually progressive disease in which the immune system attacks and degrades the function of nerve fibers in the brain and spinal cord. These nerve fibers consist of long, thin fibers, or axons, surrounded by a myelin sheath, which provides insulation and facilitates the transmission of electrical impulses. In MS, the myelin sheath is damaged by the body's own immune system, causing areas of myelin sheath loss, also known as demyelination. This damage, which can occur at multiple sites in the CNS, blocks or diminishes conduction of electrical impulses. People with MS may suffer impairments in any number of neurological functions. These impairments vary from individual to individual and over the course of time, depending on which parts of the brain and spinal cord are affected, and often include difficulty walking. Individuals vary in the severity of the impairments they suffer on a day-to-day basis, with impairments becoming better or worse depending on the activity of the disease on a given day.
Dalfampridine is a potassium channel blocker. In animal studies, dalfampridine has been shown to increase conduction of nerve signals in demyelinated axons through blocking of potassium channels. The mechanism by which dalfampridine exerts its therapeutic effect has not been fully elucidated.
Clinical Studies and Safety Profile
Our New Drug Application (NDA) for Ampyra was based on data from a comprehensive development program assessing the safety and efficacy of Ampyra, including two Phase 3 trials that involved 540 people with MS. The primary measure of efficacy in our two Phase 3 MS trials was walking speed (in feet per second) as measured by the Timed 25-foot Walk (T25FW), using a responder analysis. A responder was defined as a patient who showed faster walking speed for at least three visits out of a possible four during the double-blind period than the maximum speed achieved in the five non-double-blind, no treatment visits (four before the double-blind period and one after). A significantly greater proportion of patients taking Ampyra 10 mg twice daily were responders compared to patients taking placebo, as measured by the T25FW (Trial 1: 34.8% vs. 8.3%; Trial 2: 42.9% vs. 9.3%). The increased response rate in the Ampyra group was observed across all four major types of MS. During the double-blind treatment period, a significantly greater proportion of patients taking Ampyra 10 mg twice daily had increases in walking speed of at least 10%, 20%, or 30% from baseline, compared to placebo. In both trials, the consistent improvements in walking speed were shown to be associated with improvements on a patient self-assessment of ambulatory disability, the 12 item Multiple Sclerosis Walking Scale (MSWS-12), for both drug and placebo treated patients. However, a drug placebo difference was not established for that outcome measure.
As part of our continuing evaluation of safety, we have conducted extension studies that allowed subjects in completed clinical trials to receive Ampyra on an unblinded, or open-label, basis, with their progress followed at regular clinical visits. As of January 22, 2010, 177 subjects from our Phase 2 clinical trial had been enrolled in an extension trial and 83, or approximately 47%, remained active in the trial, with duration of treatment of active patients ranging from 5.35 to 5.9 years. As of the same date, 269 patients from our first Phase 3 clinical trial had been enrolled in a separate extension study and 173 of these, or approximately 64.3%, remained active, with duration of treatment of active patients ranging from 1.65 to 4.17 years. Also as of that same date, 214 patients from our second Phase 3 clinical trial had been enrolled in a third extension study and 165, or approximately 77%, remained active, with duration of treatment of active patients ranging from 1.78 to 2.45 years. The total exposure to Ampyra in our MS studies as of January 22, 2010, including both double-blind and open label studies, was over 2,000 patient-years. We are evaluating whether the extension studies will be continued after Amypra is commercially available.
The FDA approved Ampyra with a risk evaluation and mitigation strategy (REMS) consisting of a medication guide and communication plan. The goals of the communication plan include informing patients and healthcare providers about the serious risks, including seizures, associated with Ampyra, the importance of proper dosing, and the change of the established name from fampridine to dalfampridine. A medication guide will be dispensed to patients with each Ampyra prescription. We will implement a communication plan to support implementation of the REMS, consisting of letters to prescribers and pharmacists. In addition, the REMS includes a timetable for our submission of periodic assessments to the FDA of the REMS and patient and healthcare professional understanding of Ampyra's risks.
The FDA's approval letter also included certain post-marketing study requirements and confirmed certain commitments made by us with respect to Ampyra. The post-marketing requirements include additional animal toxicology studies to evaluate certain impurities, in vitro receptor binding and abuse potential studies in animals, and an evaluation of clinical adverse events related to abuse potential. In addition, we have committed to the FDA that we will conduct a placebo-controlled trial to evaluate a 5 mg twice daily dosing regimen of Ampyra, as well as an evaluation of a 7.5 mg dosage strength in patients with mild or moderate renal impairment. We have also committed to report all post-marketing seizure events on an expedited basis to the FDA.
In our two Phase 3 clinical studies of Ampyra in SCI, the results did not reach statistical significance on their primary endpoints. Based on the entire body of data in clinical trials of Ampyra in people with SCI, we may resume development of Ampyra for SCI in the future, but have no current plans to do so.
Biogen Idec
On June 30, 2009, we entered into the Collaboration Agreement with Biogen Idec, pursuant to which we and Biogen Idec have agreed to collaborate on the development and commercialization of products containing aminopyridines, including Ampyra, initially directed to the treatment of MS (licensed products). The Collaboration Agreement includes a sublicense of our rights under an existing license agreement with Elan. We have also entered into a related supply agreement (Supply Agreement) pursuant to which we will supply Biogen Idec with its requirements for the licensed products through our existing supply agreement with Elan. Biogen Idec Inc., the parent of Biogen Idec, has guaranteed the performance of Biogen Idec's obligations under the Collaboration Agreement and the Supply Agreement.
Under the Collaboration Agreement, Biogen Idec, itself or through its affiliates, has the exclusive right to commercialize licensed products in all countries outside of the U.S., while we retain the exclusive right to commercialize licensed products in the U.S. Each party will have the exclusive right to develop licensed products for its commercialization territory, although the parties may also decide to jointly carry out mutually agreed future development activities under a cost-sharing arrangement. If Biogen Idec does not participate in the development of licensed products for certain indications or forms of administration, it may lose the right to develop and commercialize the licensed products for such indication or form of administration. Biogen Idec may sublicense its rights to certain unaffiliated distributors. During the term of the Collaboration Agreement and for two years after the Collaboration Agreement terminates, neither party nor its affiliates may, other than pursuant to the Collaboration Agreement, research, develop, manufacture or commercialize any competing product, defined as one that contains aminopyridine or any other compound that acts at least in part through direct interaction with potassium channels to improve neurological function in MS, SCI or other demyelinating conditions, except that we may exploit the licensed products anywhere in the world following termination of the Collaboration Agreement.
In consideration for the rights granted to Biogen Idec under the Collaboration Agreement, we were entitled to a non-refundable upfront payment of $110.0 million as of June 30, 2009, which was received on July 1, 2009. Also, as a result of such payment to us, a payment of $7.7 million became payable by us to Elan. We currently estimate the revenue recognition period under the Collaboration Agreement for upfront and milestone payments to be approximately 12 years from the date of this agreement. The Company recognized $4.7 million in license revenue related to the $110.0 million received from Biogen Idec and $330,000 in cost of license revenue related to the $7.7 million paid to Elan during the year ended December 31, 2009. We are also eligible to receive up to $400 million from Biogen Idec if specified regulatory and sales milestones are met.
Under the Collaboration Agreement, we will also be entitled to receive double-digit tiered royalties on sales of licensed products by Biogen Idec, its affiliates or certain distributors outside of the U.S. Such royalties for products combining a licensed compound with at least one other clinically active therapeutic, prophylactic or diagnostic ingredient are determined based on the contribution of the licensed compound to the overall sales or value of the combination product. Biogen Idec may offset against the royalties payable to us a portion of certain royalties that it may need to pay to third parties.
Biogen Idec will exclusively purchase all of Biogen Idec's, its affiliates' and its sublicensees' requirements of the licensed products from us. The purchase price paid by Biogen Idec for licensed products under the Collaboration Agreement and Supply Agreement reflects the prices owed to our suppliers under our supply arrangements with Elan or other suppliers. In addition, Biogen Idec will pay us, in consideration for its purchase and sale of the licensed products, any amounts due to Elan for ex-U.S. sales, including royalties owed under the terms of our existing agreements with Elan.
The Collaboration Agreement will terminate upon the expiration of Biogen Idec's royalty payment obligations, which occurs, on a licensed product-by-licensed product and country-by-country basis, upon the latest of expiration of the last-to-expire patent covering a licensed product, fifteen years following first commercial sale of such licensed product, the expiration of regulatory exclusivity and the existence of certain levels of sales by competing products. The Collaboration Agreement and the Supply Agreement will automatically terminate upon the termination of our license agreement with Elan in its entirety or with respect to all countries outside of the U.S. We cannot terminate our license agreement with Elan without Biogen Idec's prior written consent under certain circumstances. Biogen Idec may terminate the Collaboration Agreement in its entirety or on a country-by-country basis at any time upon 180 days' prior written notice, subject to our right to accelerate such termination. The Collaboration Agreement may also be terminated by either party if the other party fails to cure a material breach under the agreement, which termination will be limited to a particular country or region under certain circumstances. However, if Biogen Idec has the right to terminate the Collaboration Agreement due to our material uncured breach, Biogen Idec may instead elect to keep the agreement in effect, but decrease the royalty rates they pay us by a specified percentage. We may also terminate the Collaboration Agreement if Biogen Idec does not commercially launch a licensed product within a specified time period after receiving regulatory approval for such licensed product or otherwise fails to meet certain commercialization obligations. In addition, we may terminate the Collaboration Agreement under certain circumstances if (i) Biogen Idec, its affiliates or its sublicensees challenge certain of our patents or (ii) there is a change in control of Biogen Idec or its parent company or certain dispositions of assets by Biogen Idec, its parent or its affiliated companies, followed by a change in the sales and marketing personnel responsible for the licensed products in Biogen Idec's territory of more than a specified percentage within a certain period of time after such change in control or disposition. The Supply Agreement may be terminated by either party if the other party fails to cure a material breach under the Supply Agreement. In addition, the Supply Agreement will terminate automatically upon termination of the Collaboration Agreement, and the Collaboration Agreement will terminate automatically if the Supply Agreement is terminated for any reason other than for a material breach that we are responsible for. To the extent permitted by law, each party may terminate the Collaboration Agreement and the Supply Agreement if the other party is subject to bankruptcy proceedings.
If the Supply Agreement is terminated by Biogen Idec for an uncured material breach, we will waive our right for Elan to exclusively supply the licensed products to us solely to permit Biogen Idec to negotiate terms with Elan for the supply of licensed products to Biogen Idec. If the Supply Agreement is otherwise terminated, Biogen Idec will not have any future obligations to purchase licensed products from us and we will not have any future obligations to supply Biogen Idec with licensed products. If the Collaboration Agreement is terminated, Biogen Idec will assign to us all regulatory documentation and other information necessary or useful to exploit the licensed products in the terminated countries and will grant us a license under Biogen Idec's and its affiliates' relevant patent rights, know-how and trademarks to exploit the licensed products in the terminated countries. Such assignment and license will be at no cost to us unless the Collaboration Agreement is terminated by Biogen Idec for a material uncured breach that we are responsible for, in which case the parties will negotiate a payment to Biogen Idec to reflect the net value of such assigned and licensed rights.
Neither party may assign the agreements without the prior written consent of the other, except to an affiliate or, in certain cases, to a third party acquirer of the party.
Elan Corporation plc
Ampyra
In September 2003, we entered into an amended and restated license agreement with Elan that replaced two prior license agreements for Ampyra in oral sustained release dosage form. Under this agreement, Elan granted us exclusive worldwide rights to Ampyra for all indications, including SCI, MS and all other indications. We agreed to pay Elan milestone payments of up to $15.0 million and royalties based on net sales of products with dalfampridine as the active ingredient. We also agreed to pay Elan 7% of any upfront and milestone payments that we receive from the sublicensing of rights to Ampyra or other aminopyridine products, and in the third quarter 2009, as a result of our Collaboration Agreement with Biogen Idec, we paid Elan $7.7 million. The FDA approval of Ampyra has triggered a milestone of $2.5 million to Elan that will be paid in 2010.
Elan is also obligated under this agreement to supply us with our commercial requirements for Ampyra in the U.S., as well as to supply Biogen Idec under the Supply Agreement and Consent Agreement with Ampyra for Biogen Idec's clinical trials and for Biogen Idec's commercial requirements.
Elan may terminate our license in countries in which we have a license, if we fail to file regulatory approvals within a commercially reasonable time after completion and receipt of positive data from all preclinical and clinical studies required for the related NDA equivalent. We could also lose our rights under the license agreement if we fail to launch a product in such countries within 180 days of NDA or equivalent approval or if we fail to fulfill our payment obligations under the license agreement. If Elan terminates our license in any applicable country, Elan is entitled to license from us our patent rights and know-how relating to the product and to market the product in the applicable country, subject to royalty payments to us.
We have the right to terminate the Elan license at any time by written notice. In addition, the Elan license may be immediately terminated by either party following an incurable breach of any term or provision by the other party. The Elan license may also be terminated by either party following notice and the expiration of a cure period with respect to an uncured breach by either party.
Subject to the early termination provisions, the Elan license terminates on a country by country basis on the last to occur of fifteen years from the date of the agreement, the expiration of the last to expire Elan patent or the existence of competition in that country.
Competition - MS
Current disease management approaches to MS are classified either as relapse management or disease course management approaches. For relapse management, the majority of neurologists treat sudden and severe relapses with a four-day course of intravenous high-dose corticosteroids. Many of these corticosteroids are available generically. For disease course management, there are a number of FDA-approved MS therapies that seek to modify the immune system. These treatments attempt to reduce the frequency and severity of exacerbations or slow the accumulation of physical disability for people with certain types of MS, though their precise mechanisms of action are not known. These products include Avonex from Biogen-IDEC, Betaseron from Schering AG, Copaxone from Teva Pharmaceutical Industries, Ltd., Rebif from Merck Serono, and Tysabri from Biogen-IDEC and Elan.
To our knowledge, Ampyra is the first product that is approved as a treatment to improve walking in patients with MS. This was demonstrated by walking speed. Several biotechnology and pharmaceutical companies, as well as academic laboratories, are involved in research and/or product development for various neurological diseases, including MS. Other companies also have products in clinical development, including products approved for other indications in MS, to address improvement of walking ability in people with MS. We are aware that Sanofi-aventis is developing a sodium/potassium channel blocker, nerispirdine, with a potential indication in MS and other conditions. We believe that nerispirdine is in clinical trials for walking in MS and, depending on the results of those trials, any resulting product might compete with Ampyra. BioMarin Pharmaceutical Inc. (BioMarin) acquired the rights formerly owned by EUSA Pharma to amifampridine phosphate, a 3,4-diaminopyridine compound, which in January 2010 received marketing authorization in the EU for use in Lambert Eaton Myasthenic Syndrome (LEMS). BioMarin has announced that it will be working to determine the regulatory path for approval in the U.S. for LEMS, as well as exploring developing the product for use in other indications, which may include MS. In the EU, and the U.S., if this product is successfully developed and approved, physicians might prescribe it instead of Ampyra even if it were not approved for MS. In certain circumstances, pharmacists are not prohibited from formulating certain drug compounds to fill prescriptions on an individual patient basis. We are aware that at present compounded dalfampridine is used by some people with MS. Although we expect this use to decrease substantially when Ampyra is commercially launched, it is possible that some people will continue to use compounded dalfampridine. Several companies are engaged in developing products that include novel immune system approaches and cell transplant approaches to remyelination for the treatment of people with MS. These programs are in early stages of development and may compete with Ampyra or our preclinical candidates in the future.
We believe that Ampyra may be complementary to both the relapse management and disease course management therapies that are commercially available. Nonetheless, Ampyra may compete for market acceptance with these current treatments because they have been accepted and regularly prescribed to people with MS by physicians, or because they are being promoted to improve walking or other neurological functions.
【2006】 2006.9 P3 Start for improvement of walking ability in people. In this trial, statistical significance was achieved on all three efficacy criteria defined in the SPA.In January 1997, we licensed from Elan exclusive worldwide rights to Elan’s sustained release formulation of fampridine, Fampridine-SR, for the treatment of SCI. In April 1998, we formed MS Research & Development Corporation, or MSRD, with Elan’s subsidiary, Elan International Services, Ltd., or EIS, to develop Fampridine-SR for treatment of MS. At that time, MSRD licensed from Elan exclusive worldwide rights to Fampridine-SR for the treatment of MS.In September 2003, we entered into a termination and assignment agreement with Elan, EIS and MSRD pursuant to which MSRD assigned to us its assets, including the license from Elan for Fampridine-SR for MS. We paid MSRD approximately $11.5 million for all the assets and assumed liabilities of MSRD. MSRD distributed the purchase price to its shareholders according to their equity ownership interest. We received a distribution of approximately $9.5 million. We also purchased EIS’s shares at par value, and own approximately 88% of MSRD, which now has no assets or liabilities and is inactive.
In September 2003, we entered into an amended and restated license with Elan, which replaced the two prior licenses for Fampridine-SR in oral sustained release dosage form. Under this agreement, Elan granted us exclusive worldwide rights to Fampridine-SR for all indications, including SCI, MS and all other indications. We agreed to pay Elan milestone payments of up to $15.0 million and royalties based on net sales of the product, if approved. We have not made any payments under this agreement through December 31, 2006.
Elan is responsible for completing the chemistry, manufacturing and controls section of our New Drug Application, or NDA for Fampridine-SR and equivalent regulatory applications outside the United States. Elan is also supplying us with product for our clinical trials under this agreement.
Elan may terminate our license in countries in which we have a license, including the United States, if we fail to file regulatory approvals within a commercially reasonable time after completion and receipt of positive data from all preclinical and clinical studies required for the related NDA or any NDA equivalent. We could also lose our rights under the license agreement if we fail to launch a product in such countries within 180 days of NDA or equivalent approval or if we fail to fulfill our payment obligations under the license agreement. If Elan terminates our license in any applicable country, Elan is entitled to license from us our patent rights and know-how relating to the product and to market the product in the applicable country, subject to royalty payments to us.
We have the right to terminate the Elan license at any time by written notice. In addition, the Elan license may be immediately terminated by either party following an incurable breach of any term or provision by the other party. The Elan license may also be terminated by either party following notice and a cure period with respect to an uncured breach by either party.
Subject to the early termination provisions, the Elan license terminates on a country by country basis on the last to occur of fifteen years from the date of the agreement, the expiration of the last to expire Elan patent or the existence of competition in that country.
●[Zanaflex] (tizanidine) 筋弛緩剤(痙縮/spasticity) 【2009】
Sales of Zanaflex Capsules, which we launched in April 2005, and Zanaflex tablets increased from $53.4 million for the year ended December 31, 2008 to $58.3 million for the year ended December 31, 2009. Our Zanaflex Capsules and Zanaflex tablets commercial operations were cash flow positive in 2008 and 2009. Both products are FDA-approved as short-acting drugs for the management of spasticity, a symptom of many CNS disorders, including MS and SCI. These products contain tizanidine, one of the two leading drugs used to treat spasticity. We expect sales of Zanaflex Capsules will decline in 2010 due to increasing managed care pressure, among other factors.Zanaflex Capsules and Zanaflex tablets contain tizanidine, one of the two leading active ingredients used for the management of spasticity. Tizanidine is approved by the FDA as a short-acting drug for the management of spasticity. We acquired from Elan Pharmaceuticals, Inc. (Elan) all of its U.S. sales, marketing and distribution rights to Zanaflex Capsules and Zanaflex tablets in July 2004. Zanaflex tablets were approved by the FDA in 1996 and lost compound patent protection in 2002. There are currently over 10 generic versions of tizanidine tablets on the market. However, substantial brand loyalty remains in the prescriber community for the Zanaflex brand. Most prescriptions for tizanidine tablets are written as "Zanaflex," although the majority are automatically substituted at the pharmacy for a generic tizanidine tablet. Zanaflex Capsules were approved by the FDA in 2002, but were never marketed by Elan. We began marketing Zanaflex Capsules in April 2005.
Background
Spasticity refers to the often painful involuntary tensing, stiffening or contracting of muscles. Spasticity is not a disease but a symptom of other conditions, such as MS, SCI, stroke, traumatic brain injury and cerebral palsy, where portions of the nervous system that control voluntary movement have been damaged. This damage results in the nerve cells in the spinal cord becoming disconnected from controlling centers in the brain and, as a result, transmitting unregulated impulses to the muscles. People who have spasticity may experience it intermittentlykﾀit may be triggered by a stimulus, such as pain, pressure sores, cold weather or a urinary tract infection. The majority of people with MS and SCI experience some form of spasticity, as do many people following stroke or brain injuries. We Move, a non-profit organization dedicated to movement disorders, estimates that spasticity affects approximately 500,000 people in the U.S. and over 12 million worldwide.
Clinical Studies
Clinical trials conducted by Elan demonstrated that Zanaflex Capsules, when taken with food, produce average peak levels of tizanidine in a person's blood that are lower and rise more gradually compared to the peak levels following a similar dose of the tablet form. The FDA recognizes these pharmacokinetic differences and therefore has determined that Zanaflex tablets and generic tizanidine tablets are not therapeutically equivalent, that is, are not AB-rated to Zanaflex Capsules. As a result, under state pharmacy laws, prescriptions written for Zanaflex Capsules may not be filled by the pharmacist with Zanaflex tablets or generic tizanidine tablets, although some substitution does take place in practice.
Elan Corporation plc
Zanaflex
In July 2004, we entered into an Asset Purchase Agreement with Elan pursuant to which we acquired all of Elan's research, development, distribution, sales and marketing rights to Zanaflex Capsules and Zanaflex tablets in the U.S. The assets acquired include the products' FDA registrations and FDA dossiers, proprietary product know-how, a patent and two related patent applications, certain inventory of Zanaflex tablets and certain product books and records. Elan also granted us a license allowing us to use the Zanaflex trademarks in the U.S., with the right to buy the Zanaflex trademark for a nominal sum once specified milestone and royalty payments were made. Those payments have been made, and we purchased and now own the trademarks. Elan also granted us an exclusive, perpetual and royalty-free license to certain intellectual property relating to technology contained in Zanaflex Capsules and Zanaflex tablets or used in the manufacture of Zanaflex Capsules, for use in connection with the sale and marketing of Zanaflex Capsules and Zanaflex tablets in the U.S. We also acquired the right to develop new indications, formulations, dosage forms, delivery systems and process improvements of Zanaflex. Under the agreement, Elan agreed not to directly or indirectly market, distribute or sell any products containing tizanidine as an active pharmaceutical ingredient in the U.S. until the later of the end of our obligation to pay royalties to Elan or valid termination of our supply agreement with Elan. In addition, we agreed not to directly or indirectly market, distribute or sell any products containing tizanidine as its active pharmaceutical ingredient in the United Kingdom or Ireland until July 2007.
Our agreement with Elan obligated us to pay a combination of sales-based milestone payments of up to $19.5 million, all of which have been achieved and paid, and royalties on sales of Zanaflex Capsules and Zanaflex tablets. We have no further Zanaflex milestone payment obligations with Elan. We also agreed to use commercially reasonable efforts to commercialize Zanaflex Capsules.
As part of the acquisition, we assumed certain of Elan's rights and obligations relating to Zanaflex under a license agreement with Novartis, to the extent that these rights and obligations arise subsequent to our acquisition of Zanaflex. Under this agreement we obtained certain rights to market and sell tizanidine products and rights to product improvements developed by Novartis.
Elan manufactures Zanaflex Capsules for us and we are in contract negotiations with Patheon Inc. for the manufacture of Zanaflex tablets. See "kﾀManufacturing."
In December 2005, we entered into a financing arrangement with Paul Royalty Fund, or PRF, pursuant to which we assigned PRF the right to receive a portion of our net revenues from Zanaflex Capsules, Zanaflex tablets and any future Zanaflex products. This agreement was amended in November 2006 potentially to increase the total amount of royalty payments to which PRF is entitled and to provide for additional lump-sum payments both from us to PRF and from PRF to us. The arrangement covers all Zanaflex net revenues generated from October 1, 2005 through and including December 31, 2015, unless the arrangement is terminated earlier. See "Management's Discussion and Analysis of Financial Condition and Results of OperationskﾀLiquidity and Capital ResourceskﾀFinancing Arrangements."
Competition - Spasticity
Tizanidine, the active pharmaceutical ingredient in Zanaflex Capsules, Zanaflex tablets and generic tizanidine tablets, is one of the two leading FDA-approved treatments for spasticity, a symptom suffered by both MS and SCI patients. Zanaflex tablets were approved by the FDA in 1996 and lost compound patent protection in 2002. Twelve generic manufacturers of tizanidine are distributing their own tablet formulations. As noted under "kﾀIntellectual PropertykﾀZanaflex" above, the Company is in litigation with Apotex with regard to its filing of an ANDA for the approval of a purported generic version of Zanaflex Capsules and certification against the Company's patent. In addition, several companies have reported that they are working on potential new delivery formulations of tizanidine. Baclofen, which is also available generically, is the other leading drug for the treatment of spasticity. The mechanism of action and associated effects of baclofen are different from those of tizanidine. Due to the different pharmacokinetic profile of Zanaflex Capsules, Zanaflex tablets and generic tizanidine tablets are not AB-rated with Zanaflex Capsules.
【2006】 2004.7 We acquired all marketing, sales and distribution rights in the United States to Zanaflex Capsules and Zanaflex tablets from Elan. These products contain tizanidine, one of the two leading treatments for spasticity. Zanaflex Capsules are the only approved capsule formulation of tizanidine and are protected by a patent that expires in 2021.These products contain tizanidine, one of the two leading treatments for the management of spasticity. Zanaflex tablets were approved by the FDA in 1996 and lost compound patent protection in 2002. There are currently 12 generic versions of tizanidine tablets on the market. However, substantial brand loyalty remains in the prescriber community for the Zanaflex brand. Approximately 90% of all prescriptions for tizanidine tablets are written as “Zanaflex,” although most are switched automatically at the pharmacy for a generic tizanidine tablet. Zanaflex Capsules were approved by the FDA in 2002, but were never marketed by Elan. We began marketing Zanaflex Capsules in April 2005.Clinical trials conducted by Elan demonstrated that Zanaflex Capsules, when taken with food, produce average peak levels of tizanidine in a person’s blood that are lower and rise more gradually compared to the peak levels following a similar dose of the tablet form. The FDA recognizes these pharmacokinetic differences and therefore has determined that Zanaflex tablets and generic tizanidine tablets are not therapeutically equivalent, that is, are not AB-rated to Zanaflex Capsules. As a result, under state pharmacy laws, prescriptions written for Zanaflex Capsules may not be filled by the pharmacist with Zanaflex tablets or generic tizanidine tablets, although some substitution does take place in practice. Zanaflex Capsules are available in 2 mg, 4 mg and 6 mg doses, while tablet formulations are only available in 2 mg and 4 mg doses. Our goal is to convert sales of Zanaflex tablets and generic tizanidine tablets to sales of Zanaflex Capsules. We discontinued supply of the 2 mg dose of Zanaflex tablets in February 2006 due to a reduction in demand, and we do not intend to order additional supply of this product in the future. Demand for the 4 mg Zanaflex tablet is also declining, but supports continued supply. The 6 mg capsule gives patients and physicians an additional dosing choice and an opportunity to reduce the number of pills a patient must take daily. In addition, many patients may find capsules easier to swallow than tablets. Also, people who have difficulty swallowing may open the capsule and sprinkle it on food. The pharmacokinetic effect of sprinkling contents of the capsule on food, however, is different from when the intact capsule is taken with food.
In 2006, retail sales of Zanaflex capsules, Zanaflex tablets and generic equivalents of Zanaflex tablets (tizanidine) totaled approximately $290 million. For the same period, retail sales of Baclofen totaled approximately $181 million, for an approximate aggregate market of $471 million. The vast majority of these prescriptions were written by a relatively small group of prescribers. Specialists accounted for approximately 40% of tizanidine prescribing. High-volume specialist prescribers were responsible for approximately two or three-and-one-half times more prescriptions per physician than high-volume primary care prescribers. We believe that our internal specialty sales force including our tele-sales team, will be able to reach virtually all of these high-volume prescribers.
[Spasticity 2006]
Spasticity refers to the often painful involuntary tensing, stiffening or contracting of muscles. Spasticity is not a disease but a symptom of other conditions, such as MS, SCI, stroke, traumatic brain injury and cerebral palsy, where portions of the nervous system that control voluntary movement have been damaged. This damage results in the nerve cells in the spinal cord becoming disconnected from controlling centers in the brain and, as a result, transmitting unregulated impulses to the muscles. People who have spasticity may experience it intermittently?it may be triggered by a stimulus, such as pain, pressure sores, cold weather or a urinary tract infection. The majority of people with MS and SCI experience some form of spasticity, as do many people following stroke or brain injuries. We Move, a non-profit organization dedicated to movement disorders, estimates that spasticity affects approximately 500,000 people in the United States and over 12 million worldwide.
Current treatments for spasticity are focused on reducing spasm frequency, pain or irritating stimuli that can provoke spasticity. Treatment of spasticity often involves a combination of physical therapy and oral medications. Baclofen and tizanidine, the active ingredient in the Zanaflex products, are the two most frequently prescribed oral medications for spasticity. For more intractable spasticity, treatments sometimes include surgical or chemical destruction of nerve roots in the affected area.
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●Acorda Therapeutics Inc ■Investors Relations ●News & Announcements Additional Phase 3 Clinical Trial Data Published in Annals of Neurology Showing Dalfampridine Extended Release Tablets Improved Walking Ability in People with Multiple Sclerosis[2010.11.17]
Acorda Therapeutics Reports Third Quarter 2010 Financial Results[2010.11.1] - AMPYRA(R) (dalfampridine) Extended Release Tabletsは2010.3.1発売、[Q1]$3.4 million , [Q2]$29.7 million , [Q3] $52.6 million
Acorda Therapeutics Announces Data on AMPYRA(R) (dalfampridine) Presented at 26th Congress of European Committee for Treatment and Research in Multiple Sclerosis[2010.10.15]
Acorda Therapeutics Announces Data on AMPYRA(TM) (dalfampridine) Presented at American Academy of Neurology Meeting[2010.4.13]
Acorda Therapeutics Announces Filing of Patent Extension Applications for AMPYRA(TM) (dalfampridine)[2010.3.22]
Acorda Therapeutics Announces Availability of AMPYRA(TM) (dalfampridine)[2010.3.1]
Acorda Therapeutics Announces Pricing and Patient Assistance Programs for AMPYRATM (dalfampridine)[2010.2.3]
Acorda Therapeutics Announces FDA Approval of AMPYRA(TM) (dalfampridine) to Improve Walking in People with Multiple Sclerosis - Demonstrated by Increases in Walking Speed[2010.1.22]
Acorda Therapeutics Announces Positive Vote by FDA Advisory Committee for Fampridine-SR[2009.10.14]
Acorda Therapeutics Announces Posting of Briefing Documents for October 14 FDA Advisory Committee Meeting on Fampridine-SR[2009.10.9]
Acorda Therapeutics Announces Data on Retention Rates and Safety from Two Phase 3 Fampridine-SR Extension Studies[2009.9.15]
Acorda Therapeutics Announces Interim Analysis of Two-Year Efficacy and Safety Data from Phase 3 Fampridine-SR Extension Study[2009.9.10]
Acorda Therapeutics Reports Date of FDA Advisory Committee Review of Fampridine-SR for Improvement of Walking Ability in People with MS[2009.8.25]
Biogen Idec and Acorda Therapeutics Announce Collaboration Agreement to Develop and Commercialize MS Therapy Fampridine-SR in Markets Outside the U.S.[2009.7.1]
Acorda Therapeutics Announces FDA Acceptance of Fampridine-SR New Drug Application for Filing[2009.5.6]
Study Highlights Economic Impact of Early Mobility Impairment in People with Multiple Sclerosis[2009.4.29]
Acorda Therapeutics Resubmits New Drug Application for Fampridine-SR for Improvement of Walking Ability in People with Multiple Sclerosis[2009.4.23]
Acorda Therapeutics Receives Refuse to File Letter from FDA on Fampridine-SR NDA[2009.3.31]
Data Published in The Lancet Show Fampridine-SR Improved Walking Ability in People with Multiple Sclerosis[2009.2.26]
Acorda Therapeutics Submits New Drug Application for Fampridine-SR for Improvement of Walking Ability in People with Multiple Sclerosis[2009.2.2]
Acorda Therapeutics Reports Fourth Quarter and Full Year 2007 Financial Results[2008.2.11] Acorda Therapeutics Announces Acquisition of Aminopyridine and Pre-Clinical Assets from Neurorecovery, Inc.[2008.2.4] Acorda Therapeutics Partners with Cardinal Health to Expand Sales Force for ZANAFLEX CAPSULES[2005.11.10] Acorda Therapeutics Launches ZANAFLEX(R) CAPSULES for the Management of Spasticity in People with MS and Spinal Cord Injury[2005.4.4] - Acorda社はZANAFLEX(R) CAPSULES and ZANAFLEX(R) (tizanidine HCl) tablets を1994.7 Elan Corpから取得。 今回はカプセル剤6mgを新発売。 ●SEC Filings 10-K Annual report[2010.2.26] - [pdf] - [doc] - [xls] 10-K Annual report[2007.3.26] - [pdf] - [word] - [xls] ●Anual Reports ■Products & Research ●Pipeline ●Zanaflex CapsulesTM(tizanidine hydrochloride) ●AMPYRA (dalfampridine) Extended Release Tablets
■Actelion Ltd
-http://www.actelion.com/ 創立1997.12； 本社スイス； 従業員数1,900人(2009.3); 世界に子会社１５社(日本含む) SWX Swiss Exchange (ticker symbol:ATLN)上場. Actelion Ltd Actelion Pharmaceuticals Ltd ●決算[09.01.01]SFr[CHF]=\85.19 ★パイプライン bosentan P3 Ischemic Digital ulcers in patients with systemic Sclerosis -RAPIDS-1 (RAndomized, double-blind, Placebo-controlled, multi-center Phase III study) 終了2004.12 - published in Arthritis and Rheumatism (Volume 50, Issue 12, page 3985-93). bosentan P3 Idiopathic Pulmonary Fibrosis (BUILD-1: Bosentan Use in Interstitial Lung Disease ;158例) and the scleroderma-related form of pulmonary fibrosis (BUILD-2; 162例) 2004.9開始、2005後半～2006前半終了予定 *1998.11.4 Roche社から全世界独占開発製造販売権を獲得。 tezosentan 急性心不全 開発中止(2004.11) - VERITAS (Value of Endothelin Receptor Inhibition with Tezosentan in Acute heart failure Study), for futility reasons *tezosentanは、1998.3.19 Rocheから全世界独占製造販売権を獲得。 *miglustat(Zavesca)に関して、2002.11.22 Oxford GlycoSciences (OGS)と契約。 OGSはCelltech Group plc(UCB SAに買収) に買収された。 1998年にOGSはmiglustatをG.D.Searleからライセンスを受けている。 当社はOGSからイスラエルを除く全世界独占販売権を許諾されている。 2005.11.17からroyalty支払先がOGS/CelltechからUCBに変更。 なおイスラエルでのライセンスはTevaが保有。 [2006] Actelion's second product on the market, Zavesca(R) (miglustat), achieved sales of CHF 25.4 million in 2006, almost doubling from the previous year. Zavesca(R), currently indicated for mild to moderate type 1 Gaucher patients unwilling or unable to undergo enzyme replacement therapy with Genzyme's Cerezyme(R) (imiglucerase), combines a novel mode of action with a convenient oral form. The key to capturing a greater share of the current USD 900-million market is the MAINTENANCE study, which evaluates whether patients with type 1 Gaucher disease treated with imiglucerase remain stable after switching to Zavesca(R). Recently generated clinical data with Zavesca(R) in another rare liposomal storage disease, Niemann Pick Type C, has led to a regulatory filing in the European Union to expand the label in this indication.
(CHF milllion) 2009 2008 2007 2006 2005 2004 2003 2002 2001 備考 売上 1,772.564(+23) 1,473.508(+12) 1,317.392(+) 945.7(+43) 663.6(+41) 471.9 307.5 132.4 14.0 Tracleer 1,508.0(+19) 1,294.1(+10) 1,180(+31) 898.7 633.2 449.2 299.7 121.8 3.4 (Bosentan)肺高血圧 Zavesca 53.1(+38) 40.1(+14) 35.3(+39) 25.4 14.4 6.1 0.7 - - (miglustat)[2003春に英独発売]脂質蓄積異常ゴーシェ病 Ventavis 136.9 94.6(+21) 78.2 [inhaled iloprost]肺高血圧 契約収入 74.574 44.602 25.309 21.5 16.0 16.5 7.2 10.6 10.6 営業経費 1,433.158 1,102.151(-6) 1,174.790(+) 677.5(+33) 511.3(+32) 386.3 309.2 164.5 116.6 経常利益[EBIT] 338.522 337.522
旧352.939168.274 268.2(+76) 152.3(+78) 85.6 (-1.7) (-32.0) (-102.5) 純利益 311.270 306.073
旧321.490(+158)124.586(+) 241.1(+92) 125.5(+44) 87.2 (-9.9) (-52.1) (-122.9) 研究開発費 464.136 374.530 292.137 211.8 171.5 136.3 79.2 50.6 58.7 従業員数 2,263 1,900 1028 854 660 412 263
●Actelion Ltd ■Products ●Tracleer.com --- http://www.tracleer.com/ Full Prescribing Information[pdf] Full Prescribing Information[pdf, 9p] ●Zevesca (miglustat) 1 Gaucher disease治療薬(酵素補充療法) ■Journalists ●News Archives Tracleer Excellence Post Marketing Surveillance Programme (TRAX PMSTM) confirms long-term safety profile in various pulmonary arterial hypertension subgroups[2005.9.5] JACC publication on Tracleer in children with PAH[2005.8.16] - Journal of the American College of Cardiology (JACC) が長期研究を発表 (Rosenzweig E.B. et al. Volume 46 Issue 4 Pages 697-704).８６例 Actelion launches Tracleer in PAH in Japan[2005.6.8] Japanese Approval for TracleerR in PAH[2005.4.11] Actelion provides update on bosentan in Japan[2005.2.18] Actelion files New Drug Application for TracleerR in Japan[2003.4.8] ■Scientists ●Development Pipeline ★Tracleer (bosentan)(sildenafilとの配合剤)P4 ★Zavesca (miglustat)(ゴーシェ病)P4 ★Clazosentan(動脈瘤性くも膜下出血)P3 ★Almorexant(不眠症)P3 ★Macitentan(肺高血圧)P3 ★Selexipag(肺高血圧)P3 ■Investors ●Financial Information～年報、GAAP四半期報告 Actelion announces Full Year 2008 financial results[2009.2.19] Actelion announces Full Year 2007 financial results[2008.2.21] Actelion announces Full Year 2006 financial results[2007.2.22] Actelion announces Full Year 2005 financial results[2006.2.23] Actelion announces 9-month results for 2005[2005.10.19] - In the first nine months of 2005, TracleerR sales were CHF 455.1 million (9 m onths 2004: CHF 325.4 m). 34カ国で発売 US GAAP FY 2009 US GAAP FY 2008 US GAAP FY 2007 Annual Report 2009[pdf,114p] Annual Report 2008[pdf,111p] Annual Report 2007[pdf,90p] Annual Report 2006 - [pdf] Annual Report 2005 - [pdf] Annual Report 2004 - [pdf] Annual Report 2003 - [pdf]
●アクテリオン ファーマシューティカルズ ジャパン株式会社 - http://www.actelion.co.jp/ ２００１年１０月、スイスのActelion Ltd（アクテリオン社）の１００％子会社として、東京に設立。 従業員数 １０９名（２００７年３月１日現在） ●製品情報 ★トラクリア - 医療関係者 - 添付文書[pdf] ●活動状況 ★最近の活動状況 ★ニュースリリース ●研究・開発 ★研究開発情報 ★欧米の研究・開発
■Adams Laboratories Inc.
- http://www.adamslaboratories.com/ ●会社決算(６月末) Nasdaq上場申請中"ARxT." ($Million) 2004/6 2003/6 純売上高 61.3 14.0 純利益 35.2 -23.3 従業員数 90人 1985年Adams Laboratories, Inc.は、John Q. Adams, Srにより創立。最近まで同社CEO。 同氏はBaylor Labs買収,Allerderm Labs設立に実施。 [Biz.Yahoo]Adams Laboratories, Inc. Company Profile DFBT - Event Details(2003) - John Q. Adams, Sr Interview UPDATE 2-Adams Laboratories seeks $125 mln IPO[Reuter 2005.3.25] - 私企業Adams Laboratories Inc.は$125 million相当の株式を公開。 同社主力品MucinexはSudafed[Pfizer], Nyquil[P&G], Theraflu[Novartis] ,Claritin[Schering-Plough]と競合。 関連会社●Adams Respiratory Therapeutics, Inc. -http://www.adamsrt.com/ 同社はAdams Labsの呼吸器疾患用薬剤の開発、製造、販売を目的として設立。
●Adams Laboratories Inc. ●Products ★Mucinex ★Mucinex DM 咳止め 発売September 2004 ★http://www.mucinex.com/ Mucinex DrugFacts ●News ★Press Releases ★Product Launches
■Aderis Pharmaceuticals[US]
1994.4 Ethyl Corp子会社Whitby Research Incの研究プログラム買収により設立。 1998.8 Schwarz Pharmaとパーキンソン病用パッチ剤開発で提携 2001.11 rotigotine CDS P3へ 2002.1 Discovery TherapeuticsをAderis Pharmaceuticalsに社名変更
●Aderis Pharmaceuticals -http://www.aderis.com/index.asp ●Products ★Parkinson's Disease ★Restless Legs Syndrome ★Cardiac Imaging ★Atrial Fibrillation ★Wound Healing in Diabetic Foot Ulcers ●product candidates Rotigotine(SPM-962)～パーキンソン病NDA/RLS(P2) /Schwarz社提携 Binodenoson(MRE-0470)～心臓機能診断薬 P3 /King社提携 Selodenoson(DTI-0009)～抗不整脈剤 P2 / MRE-0094～糖尿病性足部潰瘍治療薬 P1 /King社提携 ●Press Releases
■Adolor Corporation[米]
- http://www.adolor.com/ ;本社Exton, Pennsylvania 1994 創立 2000 NASDAQ上場 ●会社決算
($ 000) 2008 2007 2006 2005 2004 2003 2002 2001 ENTEREG売上 1,248 - - - - - - - [alvimopan]術後腸閉塞;FDA承認08.5、発売08.6 契約収入 48,208 9,120 15,087 15,719 25,542 20,727 総収入 計 49,456 9,120 15,087 15,719 25,542 20,727 研究開発費 52,664 41,610 56,660 49,631 48,766 56,654 販売・一般管理費 31,115 23,970 37,689 26,293 22,870 17,648 (経費計) 83,983 65,580 94,349 75,924 71,636 74,302 営業外収支 4,405 8,017 9,524 3,408 2,508 2,369 当期純利益 (30,122) (48,443) (69,738) (56,797) (43,586) (51,206) 従業員数[連結] 128 108
●Entereg(R) (alvimopan)(大腸および小腸切除術後の上部および下部消化管の回復期間短縮 【2008】Net shipments of ENTEREG through December 31, 2008 were $2.2 million. We recognized net product sales of $1.2 million on shipments to the approximately 185 hospitals that reordered ENTEREG during the year ended December 31, 2008. We have a customer deposit balance of $0.3 million at December 31, 2008. Customer deposits represent net shipments made for which payment has been received from Glaxo, but which have not yet been recognized as product sales revenue. The remaining $0.7 million difference represents product shipments for which payment has not yet been received from Glaxo and for which the conditions of revenue recognition have not been met. 【2007】Opioid analgesics provide pain relief by stimulating opioid receptors located in the central nervous system. There are, however, opioid receptors throughout the body, including the GI tract. By binding to the receptors in the GI tract, opioid analgesics can slow gut motility and disrupt normal GI function that allows for the passage, absorption and excretion of ingested solid materials. This disruption can cause patients to experience significant discomfort and abdominal pain and may result in their reducing or eliminating their pain medication. Entereg is a small molecule, mu-opioid receptor antagonist intended to block the adverse side effects of opioid analgesics on the GI tract without affecting analgesia. Entereg has been under development for both acute and chronic conditions. The acute indication is for the management of post operative ileus (“POI”), a GI condition characterized by the slow return of gut function that can result from GI or other surgeries. The chronic indication is for the treatment of opioid bowel dysfunction (“OBD”), which is a condition characterized by a number of GI symptoms, including constipation, that often results from chronic use of opioid analgesics to treat persistent pain conditions.
In April 2002, we entered into a collaboration agreement with Glaxo for the exclusive worldwide development and commercialization of Entereg for certain indications. We are responsible for the development of acute indications, such as POI, and Glaxo is responsible for the development of chronic indications, such as OBD. In the United States, we and Glaxo are co-developing Entereg and intend to share profits that result from the sale of the product. For commercial sales of Entereg for POI in the United States, we would receive 45% and Glaxo would receive 55% of the net sales less certain agreed upon costs, subject to certain adjustments. After the first three years, each party’s share would become 50%. For commercial sales of Entereg for OBD in the United States, we would receive 35% and Glaxo would receive 65% of the net sales less certain agreed upon costs, subject to certain adjustments. Under the collaboration agreement, we have the right to convert our right to receive a profit share for OBD in the United States to a royalty on net sales of 20%. Outside the United States, Glaxo is responsible for the development and commercialization of Entereg, and we would receive royalties on net sales. We may receive additional milestone payments under the collaboration agreement upon the successful achievement, if any, of certain clinical and regulatory objectives, including up to $40.0 million related to the POI indication and up to $25.0 million related to the OBD indication.
【申請経緯】2004.6 Entereg 12mg capsulesのPOIの適応でFDAにNDA申請した(４つのP3研究に基づく)。 追加のP3国際治験が実施され2005.4にFDAに追加申請。 2005.7最初のapprovable letterをFDAから受領。 2006.5に回答。 ２番目のapprovable letterを2006.11受領、2007.8に回答(OBD患者の12ヵ月長期安全性試験。リスク管理計画含む)。 2008.1 FDAはGastrointestinal Drug Advisory Committee(GIDAC)と共にEnteregの有効性と安全性を審査。2008.1.23のGIDACでは「acceleration of time to upper and lower gastrointestinal recovery following partial large or small bowel resection surgery with primary anastomosis」の適応に対して、総合ベネフィットに関して9-6、POIへの有効性には13-0(保留2)、OBD患者の12ヵ月長期安全性試験で観察された心管系イベント関連での懸念について8-6(保留1)、リスク管理計画が不十分との点に14-0(保留1)との結果。
【ライセンス】Glaxoと2002.4に全世界独占契約、2002Q2に$50 million受領。 2004Q3(NDA申請)に$10 million受領。 契約では米国でのEnteregのPOI適応での粗利のうちAdolor 45%,Glaxo 55%、OBDではAdolor 35%,Glaxo 65%、但しOBDのprofit shareを royalty 20%に変更する権利を保有。
Glaxoは2008.9 慢性OBD(オピオイド腸管機能不全)の適応に関して全世界独占契約を解消。
alvimopanはEli Lillyが創製し、1996.11にRoberts Laboratories Inc(1999.12 Shireに買収)にライセンスした。 Adolor Corporationは1998.6 Roberts社からalvimopanの全世界独占権を獲得($1.6 million)。 これとは別に2002.8 Lillyとも契約。
●Adolor Corporation ●Products ENTEREG(alvimopan)(大腸および小腸切除術後の上部および下部消化管の回復期間短縮) ●RESEARCH & DEVELOPMENT ●Investor Insights ★NEWS RELEASES ★ANNUAL REPORTS ★SEC FILINGS 10-K Annual report[2009.2.26] - [pdf] - [doc] - [xls] 10-K Annual report[2008.2.29] - [pdf] - [word] - [xls] ●PRESS ROOM - NEWS RELEASES Adolor Corporation Provides Update on R&D Programs[2008.12.18] オピオイド治療を受けている患者の慢性腸管機能不全（OBD）を対象にしたアルビモパン （alvimopan）の更なる開発はしないと発表した。 ENTEREG(R) (alvimopan) in Postoperative Ileus (POI) 承認 ENTEREG(R) (alvimopan) in Opioid Bowel Dysfunction (OBD) P3中止 ADL5859(PF-04856880) in DPN P2完了(Pfizerと共同) ADL5859(PF-04856880) in RA P2完了(Pfizerと共同) Adolor Regains Rights to Entereg(R) (alvimopan) for OBD[2008.9.2] Entereg(R) (alvimopan) Available for the Management of Postoperative Ileus[2008.6.9] Adolor and GlaxoSmithKline Announce FDA Approval of Entereg(R) (alvimopan) for the Management of Postoperative Ileus (POI)[2008.5.20]
■AEterna Zentaris Inc.[Ca]
カナダ籍企業。 従業員数200人(北米・欧州;2002) ★系列会社 Atrium Biotechnologies Inc[カナダ] 61.76% -http://www.atrium-bio.com/ Zentaris GmbH[GE] -100% ●決算 (Canada $000) 2003 2002 2001 Revenues 166,413 101,204 43,777 Operating loss (14,283) (20,566) (17,754) Loss before income taxes (18,546) (18,190) (14,844) Net loss for the year (28,147) (25,782) (3,469) ●セグメント別売上高 (Canada $ 000) 2003 2002 2001 Biopharmaceutical 46,106 315 - Cosmetics&nutrition 15,291 13,386 11,367 Distribution 105,526 87,859 32,629 連結調整 (510) (356) (219) 収入 合計 166,413 101,204 43,777
●AEterna Zentaris Inc. ●Products on the market ●Investors ★Financials ●News Room *Zentaris GmbH[GE]
●Zentaris GmbH[GE] - http://www.zentaris.de/ - 旧 Asta Medica AGから2001年分社 2003 Zentaris AGと AEterna GmbHが合併し、Zentaris GmbHになった。 2004.6 親会社Degussa AGがZentaris GmbHをAEterna Labsに売却。 バイオ医薬企業AEterna Laboratories Inc.[カナダ]の100%子会社。 →現■AEterna Zentaris Inc.[Ca] AEterna Laboratories Holds 2004 Annual Shareholder Meeting and Announces Company Name Change to Aterna Zentaris[2004.5.26] - AEterna LabがAterna Zentaris Inc.に社名変更。 100%子会社としてZentaris GmbH[GE]を傘下に持つ。 日本では、塩野義製薬にライセンス品目あり。 ●News & Facts ★Press Releases AEterna acquires German biopharmaceutical Zentaris from Degussa[2004.6.1] Degussa sells Zentaris. Divestment of the former ASTA Medica now completed[2004.6.1] - 売却価格はEur 50million; Degussa AGは、AWD pharma[Arzneimittel Dresden]をPlivaに売却(2001.6)、 腫瘍事業をBaxterに売却(2001.8)、ViatrisをAdventに売却(2002.5)。 Zentaris AGは、従業員数70人、売上高EUR 21 million(2002)、設立2001年。 ●Products, projects, services
■Affymax, Inc.
- http://www.affymax.com/ ;本社Palo Alto, CA ; NASDAQ= 2001.8 ベンチャー数社が合同で設立。 GlaxoSmithKlineからのa spin-out 2008末現在Hematideの開発に集中。現在P3(慢性腎不全による貧血、化学療法による貧血) ●会社決算★武田薬品との提携
($ 000) 2008 2007 2006 2005 2004 2003 2002 2001 提携収入 82,162 44,303 11,688 - - - - ライセンス・ロイヤリティ 689 33 38 74 151 225 103 (収入合計) 82,851 44,336 11,726 74 151 225 103 研究開発費 137,492 69,398 54,347 24,051 17,338 13,660 16,834 営業経費 計 171,582 93,473 65,436 34,083 22,269 28,944 28,448 営業利益 (88,731) (49,137) (53,710) (34,009) (22,118) (28,719) (28,345) 経常利益 (86,228) (37,712) (48,288) (32,576) (21,398) 当期純利益 (86,510) (43,069) (48,288) (32,576) (21,398) (28,197) (28,046) 従業員数[連結] 147 In February 2006, we issued an exclusive license to Takeda for the development and commercialization of Hematide in Japan. Pursuant to this agreement, Takeda has paid us approximately $37 million to date, consisting of $17 million in upfront license fees, $10 million in milestone payments, and approximately $10 million for the purchase of 530,082 shares of our Series E Redeemable Convertible Preferred Stock at a price of $18.86 per share, which we determined was at fair value. In addition, we are eligible to receive additional clinical and regulatory milestone payments of up to an aggregate of $65 million upon Takeda's successful achievement of clinical development and regulatory milestones in Japan. Takeda is responsible for all development and commercialization costs in Japan and will purchase API for Hematide from us. Assuming Hematide is approved and launched in Japan, we will receive a royalty from Takeda on Hematide sales in Japan.
In June 2006, we expanded our collaboration to develop and commercialize Hematide worldwide, which includes the co-development and co-commercialization of Hematide in the U.S. Takeda received an exclusive license to develop and commercialize Hematide outside of the U.S. Beginning January 1, 2007, Takeda will bear the first $50 million of third-party expenses related to development in pursuit of U.S. regulatory approval of Hematide. Thereafter, Takeda will bear 70% of the third-party U.S. development expenses, while we are responsible for 30% of the expenses. Each company retains responsibility for 100% of its internal development expenses. Under the June 2006 agreement, Takeda paid us an upfront license fee of $105 million, and we are eligible to receive from Takeda up to an aggregate of $280 million upon the successful achievement of clinical development and regulatory milestones. Further, we may receive from Takeda up to an aggregate of $150 million upon the achievement of certain worldwide annual net sales milestones. We and Takeda will share equally in the net profits and losses of Hematide in the U.S., which include expenses related to the marketing and launch of Hematide. Takeda will pay us a variable royalty based on annual net sales of Hematide outside the U.S. The agreement establishes a joint steering committee to oversee the development, regulatory approval and commercialization of Hematide.
We will share responsibility with Takeda for clinical development activities required for U.S. regulatory approval of Hematide. Specifically, we have primary responsibility for Hematide's clinical development plan and clinical trials in the dialysis and pre-dialysis indications, while Takeda has primary responsibility in the chemotherapy induced anemia and anemia of cancer indications. We are responsible for U.S. regulatory filings in the dialysis, pre-dialysis, chemotherapy induced anemia and anemia of cancer indications, including holding the NDAs for those indications. Takeda is responsible for regulatory filings outside the U.S. and the creation of a global safety database.
We are also responsible for the manufacture and supply of all quantities of API to be used in the development and commercialization of Hematide worldwide. Takeda is responsible for the fill and finish steps in the manufacture of Hematide worldwide.
We have agreed to jointly develop the initial commercial marketing plan for Hematide in the U.S. pursuant to which we and Takeda will divide Hematide promotional responsibilities in the U.S. We and Takeda will jointly decide on promotional responsibility for markets outside of these initial indications.
Under the February 2006 agreement, Takeda also obtained a right of first negotiation to any backup products for Hematide developed by us or our third-party partners. Specifically, during the first ten years of the agreement, if we or our third-party partners develop a product that advances to Phase 2 clinical trials and competes with Hematide in the renal or oncology indications, we are obligated to offer to Takeda the right to develop and commercialize such product in Japan before offering the product opportunity in Japan to any other third party.
We have recognized $11.7 million of revenue under our Arrangement with Takeda during the year ended December 31, 2006. In December 2006, Takeda completed a Phase 1 trial of Hematide in Japan resulting in the payment in January 2007 to us of a $10 million milestone under the collaboration.
★貧血用 EPO市場
IMS Health推計によると、2008年度rEPO製剤は世界で$11.5 billion、米国$6.8 billion。 米国主要製品はPROCRIT[J&J]およびAranesp and EPOGEN[Amgen]
Aranesp, introduced in 2001, has significant market share, particularly in the oncology market. In late 2005, U.S. quarterly sales of Aranesp surpassed those of PROCRIT. Aranesp is approved for once-monthly dosing for treatment of anemia in pre-dialysis patients in Europe. In the U.S., Amgen reportedly is in the process of seeking approval for once-monthly dosing of Aranesp for treatment of anemia in pre-dialysis patients. In 2005, Amgen submitted a biologics license supplement to include a once-monthly dosing regimen for pre-dialysis patients in the label for Aranesp. In October 2006, the FDA responded to Amgen's filing with a request for additional clinical data for the once-monthly dosing regimen, including an additional clinical study.Roche has obtained regulatory approval to market and has launched a PEGylated ESA, called Mircera, in Europe. Mircera reportedly has greater plasma stability than any of the currently marketed products. PEG is a polymer that increases the time rEPO remains in the circulation and consequently can be dosed less frequently. Mircera has also obtained regulatory approval in the U.S., but as a result of Roche and Amgen's patent infringement litigation, Mircera has been found to infringe several U.S. patents owned by Amgen and has been enjoined from being sold in the U.S. until the expiration of these patents in 2013. If Mircera enters the U.S. markets before Hematide or upon its entry, we believe that Mircera will be in direct competition with Hematide, and therefore could potentially limit the market for Hematide, because of its ability to be longer acting than currently marketed ESAs in the U.S. In addition to marketed ESAs, there are several ESA product candidates in various stages of active development, including small molecules, by a potential competitor, FibroGen, Inc., that may promote the production of naturally-occurring EPO in patients. In addition, Merck recently announced plans to develop its own version of EPO in yeast cells instead of mammalian cells which, if successful, may permit Merck to launch its product prior to the expiration of Amgen's U.S. patents.
In addition, several biosimilar versions of short-acting rEPO have recently been launched or are expected to launch in Europe in the near term. Biosimilar EPOGEN products are generally not expected to enter the U.S. market until 2013, when the last patent in Amgen's U.S. EPO patent estate expires.
According to IMS Health Incorporated, recombinant EPO, or rEPO, generated $13 billion in worldwide revenues for 12 months ended June 2006, of which we believe approximately $9 billion was generated in the U.S. Of this $9 billion, we estimate that approximately $3 billion is attributable to use of rEPO in patients on dialysis, and the remaining $6 billion is attributable to other indications, including oncology and use in predialysis patients. Despite the success of rEPO, we believe that worldwide markets for predialysis and cancer are underserved. Currently marketed rEPO is typically given up to three times per week to dialysis patients, and every one to three weeks to oncology patients. We believe the requirement for relatively frequent dosing has historically limited the use of these ESAs in predialysis and oncology treatment settings and that Hematide, with less frequent dosing, has the potential to expand these markets. While the dialysis market is currently well penetrated, we believe Hematide has the potential to offer reduced operational cost and complexity for healthcare providers compared to currently marketed ESAs
★Anemia Background
Anemia, a condition in which the blood is deficient in red blood cells and hemoglobin, is a frequent and serious complication associated with a number of common chronic diseases. Anemia is associated with chronic fatigue and, if left untreated, may increase the risk of other diseases or even death. Red blood cells are normally formed in the circulating blood from progenitor cells, known as stem cells, and from precursor cells which are initially present primarily in the bone marrow. These cells are stimulated to divide and differentiate and are mobilized into circulation by EPO, a hormonal factor produced by the kidney. EPO acts by binding to and activating the EPO receptor on precursor cells. The activation of the EPO receptor stimulates the proliferation and maturation of the precursor cells to form red blood cells that contain hemoglobin. Hemoglobin is an iron-containing protein in red blood cells that functions primarily in the transport of oxygen to, and carbon dioxide from, the tissues of the body. Anemia can be caused by conditions such as chronic kidney disease, or treatments such as chemotherapy, that result in underproduction of EPO or a muted response to EPO.
Anemia generally exists in men when the hemoglobin level in blood, which is a measure of red blood cells, is less than 12 g/dL, or the hematocrit, which is a ratio of the volume packed red blood cells to the volume of whole blood, is less than 37%, and in women when hemoglobin is less than 11 g/dL or hematocrit is less than 33%. The FDA, the medical community and others have recently raised significant safety concerns relating to currently marketed ESAs as a result of reports of increased mortality and side effects from a number of clinical trials. Some of these safety concerns relate to targeting and maintaining high hemoglobin levels for extended periods of time. The FDA recently required revised warnings, including black box warnings, be added to labels of currently marketed ESAs advising physicians to monitor hemoglobin levels and to use the lowest dose of ESA to increase the hemoglobin concentration to the lowest level sufficient to avoid the need for red blood cell transfusions. Black box warnings for currently marketed ESAs also note increased risk of death and serious cardiovascular events when administered to target a hemoglobin of greater than 12 g/dL.
★Anemia associated with Chronic Kidney Disease. One of the most common forms of chronic anemia is that which occurs in patients with chronic kidney disease. According to the American Journal of Kidney Disease, chronic kidney disease affects as many as 19 million Americans. As kidney function deteriorates due to the underlying disease, the ability of the kidney to produce adequate EPO is impaired, resulting in decreased production of new red blood cells and anemia.
Over time, chronic kidney disease usually progresses to irreversible end-stage renal disease, the most severe stage of the disease. End-stage renal disease patients require either lifetime dependence on renal dialysis, a medical procedure in which blood is cleansed of impurities, or a kidney transplant. Patients with end-stage renal disease are nearly always moderately to severely anemic unless treated with an ESA like rEPO. According to the Centers for Medicare and Medicaid Services, or CMS, there are approximately 320,000 end-stage renal disease patients on dialysis in the U.S. served by approximately 4,700 dialysis facilities. Funding and reimbursement for this care are predominately through the Medicare End Stage Renal Disease Program. In 2005, according to the CMS, reimbursement for many drugs, including ESAs, was at a rate of 106% of the average ESA sales price. This allows the dialysis facilities to realize a profit on the purchase and administration of ESAs, which constitutes an important component of their economic viability. IMS Health estimates that the U.S. sales of EPOGEN, the dominant therapy for anemia in dialysis patients, totaled $2.9 billion for the 12 months ended June 2006.
We estimate that approximately two-thirds of pre-dialysis patients with anemia are not treated with an ESA prior to progression to stage 5, end-stage renal disease, and initiating dialysis. While in the U.S., currently marketed ESAs are indicated for up to every two week dosing in predialysis, these patients often require much less frequent visits to their nephrologists or primary care physicians for treatment of their underlying disease. Because of the incongruity between the optimal dose scheduling of these ESAs and the timing of predialysis patient office visits, we believe that the predialysis market for ESAs is underserved by existing therapy and could be better served with a product that can be dosed once every four weeks.
★Anemia associated with Cancer. Anemia in cancer patients may be caused by chemotherapy or the cancer itself. For patients undergoing chemotherapy, the destruction of progenitor stem cells and precursor cells in the bone marrow by chemotherapy often leads to anemia. Severe fatigue associated with anemia affects approximately three-fourths of all cancer patients undergoing chemotherapy. In some cancer patients, such as those with multiple myeloma and acute leukemia, the underlying cancer itself causes anemia. In these patients, the production of and responsiveness to EPO is believed to be reduced by molecules known as cytokines that are produced by or in response to tumors. An oncologist's ability to treat a patient's cancer is often limited by the patient's ability to tolerate the side effects, including anemia, of highly toxic courses of chemotherapy. Better management of chemotherapy induced anemia could lead to better dose optimization of chemotherapy in cancer patients.
The FDA has recently issued a public health advisory re-evaluating the safe use of the ESA class and is scheduled to convene its Oncology Drugs Advisory Committee (ODAC) in May 2007 to consider the mechanism of action of ESAs and to review the effects of ESAs on survival and tumor progression in cancer patients. Use of ESAs has been associated with shortened time to tumor progression in certain patients with advanced head and neck cancer. Increased risk of death has been reported when ESAs are administered to target a hemoglobin of 12 g/dL in patients with active malignant disease receiving neither chemotherapy nor radiation therapy, a population for which ESAs are not approved or indicated.
Based on our marketing research, there are approximately 3 million actively treated cancer patients in the U.S. Of those patients, roughly 1.2 million undergo chemotherapy to treat their cancer. About 65% of chemotherapy patients become anemic, with 47% of those receiving ESA therapy. Further, based on the January to June 2005 Tandem cancer audit, over 90% of chemotherapy patients receive chemotherapy treatment in three or four week cycles or less frequently, yet the most prevalent dosing intervals of current ESAs for cancer patients are every one to two weeks. We believe that a less frequent, more convenient dosing regimen, every three to four weeks to coincide with chemotherapy, may increase market penetration and expand use of ESAs for oncology patients.
Anemia associated with Other Conditions. Anemia can also occur in any person with a chronic disease that causes significant inflammation, infection, or bleeding, such as rheumatoid arthritis or cardiovascular disease, and it can therefore be considered a characteristic disease of the elderly. We are testing Hematide in chronic kidney disease and cancer, but are not currently testing Hematide's effectiveness in treating anemia in other conditions.
★Current Therapy and Limitations
According to IMS Health, rEPO generated $13 billion in worldwide revenue for the 12 months ended June 2006, of which approximately $9 billion was generated in the U.S. Of the $9 billion in U.S. revenue, we estimate that $3 billion is attributable to use for dialysis patients, and the remaining $6 billion is attributable to other indications, including use in oncology and predialysis patients. ESAs, in the form of rEPO variants, have been used successfully to manage the anemia of dialysis, predialysis and cancer patients. rEPOs are similar, but not necessarily identical, to a patient's naturally occurring EPO. Differences exist among rEPOs with regard to composition and structure. As a result, differences may also exist among rEPOs with regard to frequency of dosing, duration of effect and rate of rise in hemoglobin. Stability in the blood and circulating half-life, which measure the time it takes the compound to disappear from the blood, generally correlate with less frequent dosing. One of our objectives is to develop a product with a duration of effect that results in a well-controlled hemoglobin response while still allowing optimal dosing, ideally once every four weeks.
Since its initial U.S. market introduction in 1989, rEPO has revolutionized the treatment of patients with anemia resulting from chronic diseases. To date, the therapeutic options have not progressed significantly beyond the relatively short-acting and inconvenient recombinant protein products currently on the market. Further, the majority of products in development are variations of the existing products on the market.
Two current types of ESAs, epoetin alfa and epoetin beta, are biologically engineered hormones produced in mammalian cells by recombinant DNA technology. Both are relatively short-acting forms of rEPO that typically require frequent dosing to obtain a sustained correction of anemia. Darbepoetin alfa, which is marketed by Amgen, Inc., or Amgen, under the trade name Aranesp, is a biologically engineered hormone product closely related to and functionally similar to epoetin alfa. However, darbepoetin alfa has a terminal half-life approximately three times longer than epoetin alfa, as a result of the addition of sialic acid to stabilize the protein. The currently available rEPOs are marketed under a variety of trade names in different territories.
★Frequency of Dosing. Currently marketed ESAs are hampered by short duration of effect resulting in the need for frequent dosing. We believe that the need for frequent dosing has limited the use of ESAs in treatment settings such as predialysis, where patient visits for the purpose of treating underlying disease are less frequent than for patients undergoing dialysis multiple times per week. The population of predialysis chronic kidney disease patients who may benefit from anemia management far outnumbers the population of patients who have reached end-stage renal disease. We believe the requirement for relatively frequent dosing has historically limited the use of ESAs in predialysis and oncology treatment settings and that, with its longer acting profile, Hematide has the potential to expand these markets. In the oncology setting, anemia management often involves administration of ESAs more frequently than typical chemotherapy regimens, which usually require treatment every three to four weeks. Although existing ESAs are sometimes given in larger doses in an effort to achieve extended dosing, and despite studies by the manufacturers of these ESAs aimed at extending the dose interval of these products, medical record audit data and oncologist survey response indicate that existing ESAs are still administered to chemotherapy patients once a week to once every two weeks on average. In addition, recent studies by manufacturers of ESAs indicate that the higher levels of hemoglobin associated with larger and more frequent doses result in a statistically significant increase in cardiovascular events. For these reasons, we believe that an ESA designed for every four weeks administration could expand the market opportunity for anemia management therapies in the oncology setting.
★Pure Red Cell Aplasia(赤芽球癆;純赤血球無形成症). Treatment of patients with rEPO has been shown in rare cases to cause the production of antibodies to both rEPO and naturally-occurring EPO. Typically these antibodies can bind to and neutralize both the rEPO drug and any naturally-occurring EPO in a patient's system. As a result, such patients become increasingly less sensitive to rEPO therapy and can develop a form of anemia called Pure Red Cell Aplasia, or PRCA. This hematological disorder is characterized by severe, transfusion-dependent anemia, a scarcity of reticulocytes and an almost complete absence of red blood cell precursors in otherwise normal bone marrow. Recently, the FDA has required marketers of rEPO in the U.S. to include in their product prescribing information warnings of potential for rEPO induced PRCA and a description of this adverse reaction. We believe that an ESA that does not cause PRCA and that can be used to treat PRCA will have advantages in the marketplace over rEPOs that can cause PRCA.
★Potential Hematide Advantages
Hematide is a relatively small synthetic peptide-based ESA which we are developing for the treatment of anemia in dialysis, predialysis, PRCA and cancer patients. Peptides are composed of amino acids, commonly known as the building blocks of proteins. Typically, a peptide is composed of fewer than 50 amino acids, while a protein contains from 50 to well over 5,000 amino acids. Peptide-based therapeutics may display certain advantages compared to recombinant proteins, including simplicity and cost of manufacture, and specificity of effect. Further, because they are composed of naturally-occurring amino acids, peptide-based therapeutics theoretically also carry the general advantage of reduced toxicity relative to small molecule drugs. In the past, development of peptide-based drug candidates was often slowed by low potency. A second problem historically associated with peptide-based drugs has been a requirement of frequent dosing in vivo. More recently, however, it has been possible to develop peptide-based drugs with potencies nearly equivalent to recombinant proteins and with less frequent dosing requirements.
Through the use of our technology, we have designed Hematide to require less frequent dosing than currently marketed ESAs. We believe that Hematide's properties are superior to the properties of rEPO drugs currently on the market, particularly in terms of required frequency of administration. As a long-acting ESA, we believe that Hematide may overcome many of the patient care limitations of currently marketed rEPOs. We believe that flexibility of dosing based on duration of effect will allow many patients to receive anemia management therapy concurrently with therapy for their underlying disease.
Hematide is being developed for room temperature stability, ease-of-handling and long shelf life in order to overcome many of the limitations which hamper the cost effectiveness, and thus the physician adoption, of rEPOs.
Our early clinical trials have shown similar positive effects on red blood cell formation when Hematide is given at equivalent doses either intravenously or subcutaneously. These results suggest that Hematide may be equally effective in humans when administered by either route. Additional clinical trials are underway to confirm this observation. We believe it may be easier to use Hematide than some forms of rEPO, which often have different clinical effects when given subcutaneously versus intravenously.
Although Hematide has the erythropoietic activity characteristic of naturally occurring EPO, its amino acid sequence is unrelated to EPO, rEPO or any other known naturally-occurring erythropoietic protein. Because Hematide does not appear to display immunologic cross-reactivity to naturally-occurring EPO, we believe that Hematide will not cause PRCA. We have conducted preclinical studies which have demonstrated that Hematide can stimulate reticulocytes and elevate hemoglobin levels in animal models of EPO antibody mediated PRCA. An ongoing Phase 2 clinical trial of Hematide in a small number of patients with PRCA has shown supportive results to date. These results suggest that Hematide is not neutralized by antibodies to rEPO and thus may be effective in rescuing patients that have developed PRCA.
Based on preclinical and clinical studies to date, we believe that the risk of developing antibodies to Hematide will be low. Thus far, we have observed that Hematide-induced antibodies do not appear to cross-react with rEPO and do not have any apparent effect on clinical response to the drug.
●Affymax, Inc. ●Hematide(TM) (a synthetic peptide-based erythropoiesis stimulating agent, or ESA, designed to stimulate production of red blood cells. Hematide is designed to be less frequently dosed than currently marketed ESAs, and therefore has the potential to offer both better care for patients and reduced cost and complexity for healthcare providers) P3 the treatment of anemia associated with chronic renal failure P2 for the treatment of anemia in cancer patients 前臨床 analogs for tissue protection ●R & D ■INVESTORS ●Press Releases ●Annual Reports ●SEC Filings 10-K annual report[2009.3.12] 10-K annual report[2008.3.13] 10-K annual report[2007.4.2]
■Akorn, Inc.
- http://www.akorn.com/ ; 眼科薬等の専門メーカー Akorn Manufacturing Inc.は子会社 1971 創立、Abita Springs, Louisianaにて。 droperidol(Inapsine[Akorn])を販売 ●会社決算●セグメント別売上高
($000) 2006 2005 2004 2003 2002 2001 2000 1999 収入 71,250 44,484 50,708(+12) 45,491 51,419 41,545 66,221 64,632 粗利益 26,880 14,944 18,202(+50) 12,148 20,537 6,398 28,131 33,477 営業利益 -4,905 -7,479 -368 -6,276 -3,565 -21,074 -1,731 12,122 経常利益 -5,960 -8,592 -3,018 -12,496 -6,713 -24,926 -4,014 10,639 純利益 -5,963 -8,609 -3,026 -12,325 -12,952 -15,146 -2,414 6,670 研究開発費 11,797 4,510 1,861 1,465 1,886 2,598 従業員数 371 ●研究開発 [2006] In 2006, we received 11 ANDA product approvals from the Office of Generic Drugs. As of December 31, 2006, we had 35 ANDA product submissions for generic pharmaceuticals under review at the Office of Generic Drugs: 16 from internal development and 19 from various strategic agreements with nine external partners. In most, but not all, instances we own the ANDAs that are produced by our strategic partnerships. We plan to continue to file ANDAs on a regular basis as pharmaceutical products come off patent allowing us to compete by marketing generic equivalents. See “Government Regulation” beginning on page seven.
($000) 2006 2005 2004 2003 2002 2001 2000 1999 収入 71,250 44,484 50,708 45,491 51,419 41,545 66,221 64,632 眼科用製品 19,528 22,659 29,812 26,056 29,579 16,936 注射用製品 42,489 13,719 12,341 12,155 12,977 9,663 受託製造 9,233 8,106 8,555 7,280 8,863 14,946
●Akorn, Inc. ●Investor Relations ★Overview ★News Releases Akorn, Inc. Reports Net Sales of $12.6 Million in 2004 Fourth Quarter with
Gross Margin of 33% and EBITDA of $1.0 Million[2005.2.28] ★SEC Filings 10-K[2007.3.16] - [pdf] 10-K[2004.3.30]
■AKZO Novel
Akzo Nobel's Pharma Group はOrganonを中心に、2002年度売上 Euro 140億(約1兆7374 億円)、80か国に従業員67,000人。 事業別では、医薬 EUR 40億, Coatings EUR 55億, and 化学品 EUR 46億. Akzo Nobel Announces Intended Sale of Organon BioSciences to Schering-Plough[2007.3.12] - 完全子会社Organon BioSciences N.V. (OBS)をSchering-PloughにEUR 11 billionで売却。 Akzo Nobel Confirms OBS Sale on Schedule[2007.10.11] - European Commissionが認可した。 ●会社決算会計処理は、-2003迄NL GAAP,2004-以降はIFRS ●事業別売上高
(Euro milllion) 2006 2005 2004 2003 2002 2001 2000 売上高[IFRS] 13,737(+6) 13,000 12,833 13,106 14,059 14,158 14,069 営業利益[IFRS] 1,462 1,486 1,527 1,064 1,362 1,198 1,487 純利益[IFRS] 1,153(+20) 961 945 602 818 671 947 研究開発費 885 810 807
旧823887 うちOrganon 484[18.6%] 433[17.9%] 395[17%] ●事業別従業員数
(Euro milllion) 2006 2005 2004 2003 2002 2001 2000 売上高 13,737(+6) 13,000 12,688 13,051 Ornanon 2,611(+8) 2,425 2,344 Intervet 1,125(+3) 1,094 1,027 医薬 3,246 3,600
旧3,5504,061 4,085 Coating 6,209(+12) 5,555 5,237 5,162
旧5,1445,444 5,522 化学品 3,809(-2) 3,890 4,317
旧4,1924,473
旧4,3474,679 4,680 その他 -17 36 14 10 合計 13,737(+6) 13,000 12,833 ●会社決算～医薬事業部門
(人) 2006 2005 2004 2003 2002 2001 2000 従業員数 61,880 61,340 61,450
旧61,40064,600 Organon 13,710 14,100 14,090 15,500 INTERVET 5,370 5,260 5,270 5,200 医薬 20,000 21,300 Coating 31,660 29,200 28,860 29,300 化学品 9,680 11,430 11,890
旧13,60014,400
旧14,500その他 1,460 1,350 1,340
旧1,1001,200 計 61,880 61,340 61,450
旧63,60066,400 2005年度以降はOrganonとIntervetを合算 ●製薬事業部門[Pharm]
(Euro milllion) 2006 2005 2004 2003 2002 2001 2000 売上高 3,736 3,519 3,246 3,550 4,044 3,839 2,865 営業利益 354+219 415+238 522 692 768 831 765 EBITDA 475+278 541+292 690 868 948 995 932 従業員数 19,080 19,360 20,000 21,300 21,700 21,000 21,200 1) Chefalo - 2001初めに売却 2) Organon Teknikaの診断薬部門は、bioMerieuxに売却。<2000> Organon&Organon Tekn ika計は、2,254に修正された。 Organon&Organon Teknikaは、2001.5.1統合。 3) 医薬原料メーカーDiosynth社は2005.1にOrganon社に統合 ●製品別売上
(Euro milllion) 2006 2005 2004 2003 2002 2001 2000 1999 備考 Organon 2,611(+8) 2,425 2,344
旧2,0102,279 2,593 2,504 1,980(+49%) 1,620 PRESCRIPTION DRUGS Intervet 1,125(+3) 1,094 1,027
旧1,0241,010 1,081 1,096 1,020(+26%) 515 VETERINARY PRODUCTS Diosynth - - 366 479 529 488 380(+9%) 335 ACTIVE INGREDIENTS FOR THE PHARMACEUTICAL INDUSTRY Organon Teknika - - - - - - 555(+14%) 530 HOSPITAL SUPPLIES CHEFARO - - - - - - 85(+2%) 90 NONPRESCRIPTION PRODUCTS Pharm. Total 3,736 3,519 3,246 3,550 4,008 4,044 3,839(+34%) 2,865 ★Implanon -the innovative contraceptive implant [2006] 米国FDA承認、発売2006 Late ★NuvaRing [2006] ・topped the 1.5 million user mark worldwide ・also approved for the Australian market. 32ヵ国目 ★Anesthesia revenues [2006] Anesthesia revenues grew 27%, boosted by muscle relaxant Esmeron(R) and the injectable Anzemet(R), for post-operative nausea and vomiting. Anzemet(R), which is licensed in by Organon from sanofi-aventis for the United States only, added to the already strong anesthesia franchise in the United States. ★Royalties and services revenues [2006] were mainly attributable to royalty payments from Janssen on RisperdalR sales in selected countries and from GlaxoSmithKline on sales from Arixtra(R). Service revenues were received mainly from Ligand, with whom our co-promotional collaboration on Avinza(R) was ended by the end of September 2006, although the royalty income from the product will remain for a number of years. ■Pipeline /2007.6
(Euro milllion) 2006 2005 2004 2003 2002 2001 2000 備考 � Contraception 669(+18) 564(+8) 522(+4) 517(+7) 521(-3) 540(+10%) 492(+20%) うちNuvaRing 213(+67) 127(+57) 81(+115) - - - - [Etonogestrel/Ethinyl Estradiol Vaginal Ring]避妊リング Marvelon/Mercilon/Mircette - 390(-12) 431(+6) ??? - [desogestrel/ethinylestradiol](oral contraceptives) � Hormone Replacement Therapy - 330(+5) 314(+11%) Livial 151(-2) 154(-4) 160(-17) 197(-1) 208(+12) 186(+20%) 155(+40%) [tibolone](hormone replacement)世界90ヵ国 � Infertility - 402(+5) 384(+10%) - - Puregon/Follistim 384(+8) 355(+20) 285(-11) 331(-1) 356(+8) 329(+17%) 282 [follitropin beta](infertility product) � Depression - 800(+11) 720(+39%) - - Remeron 253(-11) 283(-22) 363 524 717(+14) 627(+51%) 414(+58%) [mirtazapine](antidepressant) 米国 47(-75) 208(-45) 米国外 316(-) 316(+26) � Hospital pharmaceuticals* - 282(+3) 272(-2%) Pharmaceutical ingredients 255(+2) 228(+8) Anesthesia 242(+28) [] from Form 20F 2006[pdf,239p;2006.6.22] p25 Currently, 39 compounds are in various stages of the development pipeline: 23 in pre-clinical development, 7 in Phase I clinical development, and 4 in Phase II clinical development, of which two are in advanced stages of Phase II developmen t. Five products are in Phase III clinical development. ●Annual Report 2003 -General[pdf,55p] - 53p★[Products and Markets - Pharma]Main human healthcare products in the pipeline (Phase II and later)
Project Application Phase Description ●Gynecology Org 50081 Serotonin -2-Blocker (hot flushes) III NOMAC/E2 Oral contraceptive in-licensed from Theramex (Merck KGaA) III Org 39970 Androgen II ●Fertility Org 36286 Sustained Follicle Stimulant(corifollitropin alpha) III ●Neuroscience asenapine dopamine/serotonin antagonist III Org 50081 Serotonin-2-Blocker (insomnia) III farampator AMPAkine II Org 34517 GR antagonist II Org 25935 GlyT1 inhibitor II ●Anesthesia sugammadex Selective muscle relaxant binding agent III ●Other Org 42675 Antithrombotic dual inhibitor II/X II
Project Application Phase Launch Description Org 33628 Contraceptive II (progesteron receptor modulator) "Male pill" contraceptive II >2005 (androgen/progestagen combination) FSH-CTP infertility II long-acting FSH Livial 1.25mg HT/osteoporosis III Selective tissue estrogenic activity regulator (STEAR); 規格追加 Variza(R)
depression filed 5HT-1A partial agonist Asenapine/Org 5222 psychosis III 2005 DA/5HT-antagonist Org 24448 psychosis II AMPAKINE Org 34517/34850 depression II HPA axis modulator Org 4420 sleep II NASSA Org 25969 Anesthesia II muscle relaxant binding agent Org 37663 immunology II anti-inflammatory steroid Org 39141 immunology II auto-antigen ●終了分 NuvaringR contraceptive ring approved 2002 発売 Implanon[R] contraceptive implant market 2000(Europe) III 2002/3(USA) Puregon Pen. infertility launched 2001 (Europe) 申請 2003 (USA) Xyvion. osteoporosis III 2004 (USA) AndriolR Testocaps. male HRT III 2002 (Europe) 申請 2004 (USA) Org 34517 depression II 2006 Arixtra thrombosis market 2002 (USA) filed 2002 (Europe) SanOrg 34006 thrombosis III >2005 Org 39141 rheumatoid arthritis II 2007
●AKZO Novel Akzo Nobel Announces Intended Sale of Organon BioSciences to Schering-Plough[2007.3.12] - 完全子会社Organon BioSciences N.V. (OBS)をSchering-PloughにEUR 11 billionで売却。 Akzo Nobel Confirms OBS Sale on Schedule[2007.10.11] - European Commissionが認可した。 ●Healthcare ★Healthcare Activities ★Products ★[Business] Organon ●News & Media - NewsとPressReleaseの違いは曖昧だが、重複はないので、双方Check要 ★News & Features --最近のものだけ Pressroom -PressRelease - 期間・部門指定検索(最新含む) Pressroom -News Stories - 期間・部門指定検索(最新含む) ★Reports & Presentation～決算資料 ■Investor Relations ●News & Publications ●Financial Press Releases ★Reports & Presentation～決算資料 Form 20F 2006[pdf,239p;2006.6.22] Form 20F 2005[pdf,210p;2006.6.26] ●Annual Report Annual Report 2007[pdf,p,2008.2.19] Annual Report 2006[pdf,136p,2007.3.14] Annual Report 2005[pdf,2006.2.28] Annual Report 2004 Annual Report 2003 Annual Report 2002 ●Financial Overview
●N.V. Organon --- http://www.organon.com/ ■News ■Product ●Gynecology - www.orgyn.com ★Contraception - www.contraception.net NuvaRing(R) (etonogestrel/ethinylestradiol) Cerazette(R)(desogestrel) Gracial(R)(desogestrel / ethinylestradiol) -22-day combiphasic Implanon(R)(etonogestrel) -a single-rod contraceptive implant Laurina(R)(desogestrel / ethinylestradiol) Marvelon(R) / Desogen(R)(desogestrel / ethinylestradiol) Mercilon(R) / Mircette(R)(desogestrel / ethinylestradiol) ★Hormone Therapy - Managing the menopause Livial(R)(tibolone) - http://www.livial.com/ Ovestin(R)(estriol) Riselle(R)(17s-estradiol implant) Andriol(R)(testosterone undecanoate) - http://www.andriol.com/ ●Feretility - http://www.fertilityjourney.com/ Orgalutran(R)(ganirelix) - reduces IVF (in-vitro fertilization) treatment time Pregnyl(R)(human chorionic gonadotropin) since 1932 Puregon(R) / Follistim(R) (follitropin beta) since 1996 - http://www.puregon.com/ ●Neuroscience - Mental Health ●Anesthesia
●日本オルガノン - http://www.organon.jp/ ●プレスリリース 「OCケータイ情報」サイト開設のお知らせ[2005.11.9] 低用量経口避妊剤「マーベロン(R)21」発売のお知らせ[2005.4.19] - マーベロン(R)21は20年以上前に欧州で初めて発売されて以来現在最も普及している経 口避妊剤のひとつとして、世界80カ国以上、400万人を越える女性に使用。 日本において低用量経口避妊剤を服用している女性の数は、1999年以降毎年10%以上の増 加をみせており、現在では50万人を上回るとみられています。 ●製品 ●医療関係者向けの情報 ★製品一覧 ★泌尿器科領域 ★産科婦人科領域 ファティリティー.jp - https://www.fertility.jp/ 自分で選ぶＯＣ(ピル) - http://www.oc-rizum.jp/ ★精神科・神経科・心療内科領域 ★循環器科・内科領域 ★麻酔科領域 ★その他の治療領域 ●アクゾノーベル株式会社 ---
■Alcon Laboratories,Inc.
- http://www.alconlabs.com/; (2007)売上$5.6 Billion、従業員数14,500 1945 設立 1977 Nesle SAに買収、傘下に入る。 * しかしAlconで決算データを発表しているし、ネスレ社でのAlcon情報は殆どない。 2000 Summit Autonomous Inc.を買収。 ●会社決算
($ milllion) 2009 2008 2007 2006 2005 2004 2003 2002 2001 売上高 6,499 6,294 5,599 4,897 4,368 3,914 3,407 営業利益 2,261 2,213 1,883 1,572 1,188 1,132 879 経常利益 2,313 2,083 1,929 1,617 1,203 1,126 858 当期純利益 2,007 2,047 1,586 1,348 931 872 595 研究開発費 665 619 564 512 422 390 350 従業員数[連結] 15,700 14,500 *消費者アイケア は2004年度迄は「コンタクトレンズ」 ●事業別売上
($ milllion) 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 ★米国 眼科医薬品 1,353[46.4%] 1,321[47.1%] 1,279.5(+9.3)[47.9%] 1,170.6(+11.7)[47.5%] 1,047.7[47.7%] 941.3(+15.7) 813.3(+15.1) 706.9 582.9 513.9 眼科手術製品 1,167[40.1%] 1,084[38.6%] 1,011.8(+6.5)[37.9%] 950.4(+9.2)[38.6%] 870.1[39.6%] 778.0(+9.0) 713.8(+5.2) 678.3 639.7 589.2 消費者アイケア* 394[13.5%] 402[14.3%] 381.2(+11.2)[14.2%] 342.7(+23.5)[13.9%] 277.6[12.7%] 271.0(+4.7) 258.8(+4.6) 247.4 242.0 230.3 計 2,914[100%] 2,807[100%] 2,672.5(+8.5)[100%] 2,463.7(+12.2)[100%] 2,195.4[100%] 1990.3(+11.4) 1785.9(+9.4) 1632.6 1464.6 1333.4 ★国外 眼科医薬品 1,324[36.9%] 1,240[35.6%] 1,034.3(+23.6)[35.3%] 836.6(+16.2)[34.4%] 720.0[33.1%] 601.3(+21.1) 496.6(+20.7) 383.5 344.9 322.3 眼科手術製品 1,830[51.1%] 1,797[51.5%] 1,488.0(+18.7)[50.9%] 1,253.4(+9.3)[51.5%] 1,146.8[52.8%] 1036.4(+18.8) 872.1(+4.0) 760.2 718.0 674.7 消費者アイケア* 431[12.0%] 450[12.9%] 404.8(+18.1)[13.8%] 342.9(+11.9)[14.1%] 306.3[14.1%] 285.6(+13.2) 252.3(+3.1) 232.8 220.2 223.2 計 3,585[100%] 3,487[100%] 2,927.1(+20.3)[100%] 2,432.9(+12.0)[100%] 2,173.1[100%] 1923.3(+18.6) 1621.0(+8.5) 1376.5 1283.1 1220.2 ★合計 眼科医薬品 2,677(+4.5) 2,561(+10.7) 2,313.8(+15.3) 2,007.2(+13.5) 1,767.7 1542.6(+17.8) 1309.9(+20.1) 1090.4 - - 眼科手術製品 2,997(+4.0) 2,881(+15.3) 2,499.8(+13.4) 2,203.8(+9.3) 2,016.9 1818.4(+14.4) 1585.9(+10.2) 1438.5 - - 消費者アイケア* 825(-3.2) 852(+8.4) 786.0(+14.6) 685.6(+17.4) 583.9 556.6(+8.9) 511.1(+6.4) 480.2 - - 合計 6,499(+3.3) 6,294(+12.4) 5,599.6(+14.4) 4,896.6(+12.1) 4,368.5 3913.6(+14.9) 3406.9(+9.0) 3009.1 2747.7 2553.6
($ milllion) 2009 2008 2007 2006 2005 2004 2003 2002 2001 備考 感染症・抗炎症薬 829(-5.1) 874 814.5(+11.5) 730.2(+14.5) 641.0 572.7(+10.6) 517.9(+16.1) 446.0 365.2 (うちTobradex) - (?) (195.1) (176.0) [tobtamycin+dexamethasone] (うちCiloxan) - (?) (105.8) (88.3) [ciprofloxacin] 緑内障薬 1,121(+17.4) 955 830.1(+19.6) 693.8(+11.7) 621.4 526.3(+21.7) 432.4(+23.7) 349.6 276.1 (うちTravatan) - (135.3) (70.9) (15.8) [travoprost] アレルギー薬 486(+5.0) 463 446.8(+15.6) 386.6(+8.1) 357.5 321.4(+16.2) 276.6(+24.0) 223.1 181.1 [/Patanol(R)等] (うちPatanol) -(+17.9) (252.0)+27% (198.3) (154.5) [olopatadine HCl] 耳鼻科用薬 355(+12.3) 316 257.0(+8.4) 237.0(+10.1) 211.9 171.3(+39.4) 122.9(+37.0) 89.7 68.2 [/Cipro HC Otic] 他の医薬品等 (114) (47) (34.6)(*) (40.4)(*) (64.1) (49.1)(*) (39.9)(+121.7) (18.0) - 医薬品 計 2,677(+4.5) 2,561 2,313.8(+15.3) 2,007.2(+13.5) 1,767.7 1542.6(+17.8) 1309.9(+20.1) 1090.4 927.8 IOL[眼内レンズ] 1,133(+5.6) 1,073 919.4(+15.7) 794.4(+15.2) 689.4 583.9(+17.1) 498.6(+13.9) 437.7 405.4 白内障・硝子体手術用 1,759(+4.0) 1,692 1,528.8(+12.6) 1,357.7(+6.8) 1,271.3 1167.7(+14.8) 1017.0(+9.7) 927.0 875.7 屈折外科用 105(-9.5) 116 51.6(-0.2) 51.7(-8.0) 56.2 62.8(-10.7) 70.3(-4.7) 73.8 76.6 眼科手術製品 2,997(+4.0) 2,881 2,499.8(+13.4) 2,203.8(+9.3) 1,016.9 1814.4(+14.4) 1585.9(+10.2) 1438.5 1357.7 コンタクトレンズ消毒剤 448(-4.5) 469 440.2(+18.8) 370.6(+26.7) 292.6 298.9(+5.9) 282.2(+2.6) 275.1 250.9 [/Opti-Free(R)液] 人工涙液 283(+4.0) 272 233.2(+16.4) 200.4(+17.3) 170.8 141.5(+20.6) 117.3(+18.2) 99.2 96.5 その他 94(-15.3) 111 112.6(-1.7) 114.6(-4.9) 120.5 116.2(+4.1) 111.6(+5.4) 105.9 114.8 消費者向けEye Care 825(-3.2) 852 786.0(+14.6) 685.6(+17.4) 583.9 556.6(+8.9) 511.1(+6.4) 480.2 462.2 TOTAL SALES($) 6,499(+3.3) 6,294 5,599.6(+14.4) 4,896.6(+12.1) 4,368.5 3913.6(+14.9) 3406.9(+13.2) 3009.1 2747.7
●TRAVATAN(R) 緑内障 【2007】
Our line of glaucoma products provided the largest percentage of sales growth. Combined sales of our family of TRAVATAN(R) products, including TRAVATAN(R) ophthalmic solution, TRAVATAN Z(R) ophthalmic solution and DuoTrav.
ophthalmic solution, grew 30.9% for the year ended December 31, 2007 compared to 2006. TRAVATAN Z(R) enables doctors to help glaucoma patients with a benzalkonium chloride ("BAC") free prostaglandin. The U.S. commercial launch of TRAVATAN Z(R) began in October 2006 and we launched this product as TRAVATANZ. ophthalmic solution in Japan during the fourth quarter of 2007. In the second quarter of 2006, we launched DuoTrav(TM), a combination of the prostaglandin analogue travoprost with the beta blocker timolol, in several European Union countries, Canada and Australia. During the year ended December 31, 2007, Azopt(R) ophthalmic suspension, the Company's topical carbonic anhydrase inhibitor, posted a 20.4% sales increase compared to 2006, driven by growth in both the U.S. and International markets. In 2001, we launched TRAVATAN(R), our entry into the prostaglandin analogue class of glaucoma treatments, in the United States. Prostaglandin analogues are the largest class of compounds currently available to reduce intraocular pressure, which is a primary characteristic of glaucoma. We have continued to improve and enhance the TRAVATAN(R) brand with the launch outside the United States of DuoTrav. ophthalmic solution, which combines the prostaglandin in TRAVATAN(R) with a beta blocker, timolol, and with the launch in both the United States and international markets of TRAVATAN Z(R) ophthalmic solution, a new formulation of TRAVATAN(R) that replaces the preservative benzalkonium chloride ("BAC") with the SOFZIA(R) preservative system. Brands containing our proprietary prostaglandin have been launched in more than 100 countries, including an approval in Japan obtained before the end of 2007.●Vigamox(R) ophthalmic solution(moxifloxacin) 感染 【2007】
Sales of Vigamox(R) ophthalmic solution, our leading anti-infective fluoroquinolone drug, increased 16.1% compared to 2006, due to increased sales around the world as physicians continued to convert to Vigamox(R) from older anti-infective drugs.
Sales of TobraDex(R) ophthalmic suspension and ointment, our leading combination therapy for infection and inflammation, increased 8.1% during the year ended December 31, 2007 over the prior year. Our leading ocular anti-infective product is Vigamox(R) ophthalmic solution, utilizing moxifloxacin to treat bacterial conjunctivitis. According to the Wolters Kluwer Health Source Prescription Audit, Vigamox(R) was the leading ophthalmic topical antibiotic in the United States in 2007. During 2006, we received approval and launched Vigamox(R) in Japan under the trade name Vegamox(R) ophthalmic solution.【2007特許】 VigamoxはAlconがBayer Healthcare AGからライセンスを受けていて、特許の２つ はBayer Healthcareが保持、３つ目はAlconが保持するもので2020年迄。 Teva Pharmaceuticals USA, IncがApril 5, 2006最初のANDA申請●NEVANAC(R) ophthalmic suspension 抗炎症 【2007】
NEVANAC(R) ophthalmic suspension is our ophthalmic non-steroidal anti-inflammatory drug ("NSAID") for the treatment of pain and inflammation associated with cataract surgery. Sales of NEVANAC(R) grew 30.0% in the year ended December 31, 2007 over the prior year. During 2005, we launched a topical non-steroidal anti-inflammatory drug ("NSAID") in the U.S. market for the treatment of pain and inflammation associated with cataract surgery. NEVANAC(R) ophthalmic suspension is unique because it is a prodrug where the active ingredient is released upon instillation in the eye. During 2007, NEVANAC(R) maintained the number two NSAID market share in the United States, according to Wolters Kluwer Health Source Prescription Audit. We also executed several launches of NEVANAC(R) outside the United States during 2007.●Patanol(R)点眼液 アレルギー 【2007】
Despite relatively flat growth in the U.S. allergy market, global sales of our allergy products, Patanol(R) ophthalmic solution and Pataday. ophthalmic solution, grew 16.5% in the year ended December 31, 2007 over 2006. An important contributor to this above-market growth was the U.S. launch of Pataday(TM), the only once-a-day ocular prescription allergy medicine, that led to total allergy franchise market share gains as reported by Wolters Kluwer Health Source Prescription Audit. Patanol(R) product sales also were supported by faster growth outside the United States, due in part to the market share gained by this product in the spring allergy season in 2007 in Japan, where it was launched in September 2006. Patanol(R) ophthalmic solution was the first ocular allergy product with a dual-action active ingredient, which acts as both an antihistamine and a mast-cell stabilizer. According to Wolters Kluwer Health Source Prescription Audit, Patanol(R) was the leading ophthalmic topical anti-allergy prescription product in the United States in 2007. During 2006, we received approval and launched Patanol(R) in Japan, the second largest ophthalmic allergy market. We have a co-marketing agreement in Japan with Kyowa Hakko Kogyo Co., Ltd. (Kyowa Hakko), a leading Japanese pharmaceutical company, whereby Kyowa Hakko promotes Patanol(R) to non-eye care physicians and we promote the product to eye care physicians. In February 2007, we launched in the United States the first and only once-a-day ocular prescription allergy medicine, Pataday. ophthalmic solution, which is a new formulation of olopatadine, the active ingredient in Patanol(R). We currently sell Patanol(R) in more than 90 countries.【2007特許】 Patanolの特許は協和発酵が保持し2010年迄。 もう一つは協和とAlconが共同で2015年迄。 カナダApotex Inc. and Apotex CorpがANDA申請し、協和とAlcon両社は2006.11.15提訴。 そのため、提訴が解決あるいは地裁がFDA承認の30ヵ月保留を変更しない限り、FDAはApotexのANDA申請を 30ヵ月遅らせねばならない。 次にBarr Laboratories, IncがPatanolのANDA申請を行い、2007.10.1 Alcon社にその旨通知された。 Apotex ANDAと異なり、Barr ANDAは協和発酵単独特許に関するもの。 FDAがBarr ANDAを承認可能な30ヵ月後は、協和発酵特許失効の９ヵ月前のの2010.3に含むことになる。●CIPRODEX(R) otic suspension 耳科感染 【2007】
U.S. sales of CIPRODEX(R) otic suspension were primarily responsible for an 8.4% increase in global sales of otic products during the most recent year. (CIPRODEX(R) is a registered trademark of Bayer AG, licensed to Alcon by Bayer Healthcare AG.) The vast majority of CIPRODEX(R) otic sales occur in the United States. According to Wolters Kluwer Health Source Prescription Audit, total U.S. prescriptions for CIPRODEX(R) otic increased 5.4% in the year ended December 31, 2007, while total U.S. prescriptions in the otic segment of the market declined 3.4%. We also market combination anti-infective/anti-inflammatory products for ear infections. CIPRODEX(R) otic suspension for the treatment of otitis media in the presence of tympanostomy tubes ("AOMT") and of otitis externa, commonly known as swimmer's ear, is marketed in the United States and a small number of countries outside the United States. In addition, Cipro(R) HC Otic, for the treatment of otitis externa, is currently marketed in over 30 countries. Sales of our otic products are seasonal, with a higher percentage of prescriptions written during the summer months.● 【2007】
●Alcon Laboratories,Inc. - http://www.alconlabs.com/ ●Products ●Healthcare hProfessional ●Patients & Family ■Investors & Media ●Financials ★Annual Reports & Quaterly Reports - 2009 Annual Report - 2008 Annual Report - 2007 Annual Report - 2006 Annual Report - 2005 Annual Report - 2004 Annual Report ★SEC Filings - 2009 Form 20-F[16-Mar-2020] - [pdf,220p] - 2008 Form 20-F[17-Mar-2009] - [pdf] - Form 20-F[18-Mar-2008] - [pdf] - Form 20-F[19-Mar-2007] - [pdf] - Form 20-F[15-Mar-2006] - [pdf] - Form 20-F[15-Mar-2005] - [pdf] - ●Press Release - Alcon's Fourth Quarter Sales Rise 14.5 Percent[2010.2.11] - Alcon Fourth Quarter Diluted EPS Increased 12.8 Percent[2009.2.11] - Alcon's Fourth Quarter Sales Rise 20.0 Percent[2008.2.6] - Alcon's Fourth Quarter Sales Rise 16.1 Percent[2007.2.7]
●日本アルコン -http://www.alconlabs.com/jp/ 1973年に日本企業との合弁会社(「帝人アルコン株式会社」)として事業を開始。 1978年にアルコンの100％出資となり、社名を「日本アルコン株式会社」と変更。 サージカル事業/医薬品事業/ビジョンケア事業 1992 眼灌流・洗浄液「ビーエスエスプラスR」発売。 1993 超音波白内障手術装置「20000レガシーTM」発売。 フォールダブル眼内レンズ「アクリソフR」発売。 1994 緑内障・高眼圧症治療剤「ベトプティックR0.5％点眼液」発売。 1995 眼科手術補助剤「プロビスクR」発売。 1996 ソフトコンタクトレンズ用コールド消毒液「オプティ・フリーR」発売。 超音波白内障手術装置「ユニバーサルRＩＩ」発売。 1997 ソフトコンタクトレンズ用コールド消毒液「オプティ・フリー （マルチパーパスソリューション）」発売。 硝子体手術装置「アルコンアキュラスR」発売。 眼科用超音波診断装置「アルコンウルトラスキャン」発売。 2002 創立30周年を迎える。 ソフトコンタクトレンズ用コールド消毒液「オプティ・フリー プラスR （マルチパーパスソリューション）」発売。 眼圧降下剤「エイゾプト(R) １％点眼液」発売。 2003 フォールダブル眼内レンズ 「アルコン アクリソフ シングルピース SA30AT/SA60AT」発売。 超音波白内障手術装置「インフィニティRビジョンシステム」発売 ●アイケア情報 ●医療関係者のページ[要ID] ～アルコン製品、学会セミナー等
■Alfa Wassermann S.P.A.[伊]
- http://www.alfawassermann.it/index.php 設立 1948年。 私企業。 年報などの詳細データは非公開。 従業員数1000人超うちイタリア国内663人(2005.5.9 News) 子会社－ポーランド(2004.1創業)、中国、チュニジア、ハンガリーの四カ国 2003.2 Bama-Geve(スペイン製薬会社)買収完了 2004.2 Farmigea SpA[イタリア眼科・婦人科領域の製薬会社]の35%を取得。 2004 Pomezia工場売却交渉開始(2005年前半完了) 2004 Helena Laboratoriesのイタリア事業部門を買収。(2005年5.9完了) (Electrophoresis & Coagulation systemの国際企業) 2005.2 Biosaude(ポルトガルの製薬会社)を買収完了 2005年度売上高予想210 Million Euro(+12%)。 ●決算[12月決算] (千Euro) 2004 2003 2002 売上高 186,458 172,919 180,584 EBIT 16,321 10,363 18,113 EBITDA 33,813 28,628 29,501 純利益 4,884 7,499 4,766 ●セグメント別売上高 (千Euro) 2004 2003 2002 Pharmaceuticals 125,733 111,694 103,626 Diagnostics 39,881 40,702 42,944 Others 20,844 20,523 19,197 分離済み事業 - - 14,817 合 計 186,458 172,919 180,584 from Alfa Wassermann: the consolidated balance sheet as of December 31, 2004[2005.7.11] ●主力製品 Rifaximin (伊国内名Normix) - 自社開発品でスペイン・米国等12か国で承認。 Alfaferone(天然interferon-α) Fluxum (parnaparin -低分子ヘパリン) 世界６５カ国で１２製品を販売。One of the strong points of Alfa Wassermann SpA is that more than 60% of turnover is generated by its own products, developed by in-house research.
These include market leaders such as Normix®, an innovative antibiotic with a topical intestinal activity, discovered and patented by Alfa Wassermann. Other important specialities are Alfaferone® (Alfa natural interferon) and Fluxum® (Parnaparin - patented low molecular weight heparin). Alfa Wassermann also has a Division marketing and selling non prescription specialities with an extensive network of direct promoters to pharmacies.[The International Division] In 1989, Alfa Wassermann set its own International Division with two main aims - to increase exports of its speciality drugs by exploring new territories and to promote the international development of its original products with a network of strategic alliances. Today Alfa Wassermann operates with a portfolio of 11 products in more than 60 countries throughout the world and an efficient network of distributors, efficiently backed by an in-house organisation able to provide all the assistance required.
Normix® (Rifaximin) is one of the main products abroad and has significant growth prospects.
The product internationalization plan is starting to give results.
Rifaximin is today registered in 12 countries and in October 2004 the product, under the name Spiraxin®, was introduced into the market in Spain by Bama-Geve S.L. and another Alfa Wassermann licensee company.
But the most important goal was without doubt the launch of the drug on the USA market under the name Xifaxan・
●Alfa Wassermann S.P.A.[伊] ●Press Releases Alfa Wassermann: the consolidated balance sheet as of December 31, 2005[2006.5.15] Alfa Wassermann: the consolidated balance sheet as of December 31, 2004[2005.7.11] JAPANESE LICENSEE FOR LICOFELONE[2004.5.28] - 本剤はMerckle GmbHにより創製され、the Euroalliance consortium内部で Alfa Wassermann SpA, Merckle GmbH and Lacer SA の共同開発する革新的消炎鎮痛剤。 住友製薬に変形性関節症の適応症で日本での独占権を付与する契約を締結。 FDA Approves rifaximin[2004.5.26] - 商品名Xifaxanとしてライセンス先Salix社から販売予定。(適応症－大腸菌感染による下痢) Alfa Wassermann: the consolidated balance sheet as of December 31, 2003 [2004.7.15]
Alkermes, Inc.[US]
■Alkermes, Inc.
- http://www.alkermes.com/ ;(Nasdaq) ALKS; 88 Sidney Street,Cambridge, MA 02139 1987.6 MITの４人の研究者が設立。 ●会社決算 [３月決算]●相手先部収入内訳 [３月決算]
($000) 2009/3 2008/3 2007/3 2006/3 2005/3 2004/3 2003/3 2002/3 2001/3 備考 収入 Vivitrol売上 4,467 - - - - - - - - [naltrexone持続注]アルコール依存症１月１回:Cephalonと共同 製造収入 116,844 101,700 105,416 64,901 40,488 25,736 14,317 - Royalty収入 33,247 29,457 23,151 16,532 9,636 3,790 1,165 - 研究開発契約収入 42,087 89,510 74,483 45,883 26,002 9,528 31,784 54,102 Net collaborative profit 130,194 20,050 36,915 39,285 - - - - 総収入 計 326,839 240,717 239,965 166,601 76,126 39,054 47,266 54,102 経費 製造原価 43,396 40,677 45,209 23,489 16,834 19,037 10,910 - 研究開発費 89,478 125,268 117,315 89,068 91,065 91,097 85,388 92,092 販売・一般管理費 59,008 59,508 66,399 40,383 28,823 26,029 26,694 24,387 リストラ費用 - 6,423 - - 11,527 -208 6,497 - 原価・経費 合計 191,882 243,506 228,923 152,940 148,249 135,955 129,489 116,479 営業利益 134,957 (2,789) 11,042 13,661 (72,123) (96,901) (82,223) (62,377) 当期純利益 130,505 166,979 9,445 3,818 (73,916) (102,385) (106,898) (61,355) 従業員数 570 760
($000) 2009/3 2008/3 2007/3 2006/3 2005/3 2004/3 種類 内訳 Janssen [46%] [52%] [47%] 82,798[49%] 50,446[66%] 28,488[73%] 製造&Royalty RISPERDAL CONSTA;持続性製剤で75ヵ国承認、発売は米国含む55ヵ国 Cephalon [41%] [11%] [24%] 39,285[24%] - - 2005.6 持続性naltrexone製剤Vivitrolの共同開発・製造・販売契約。本剤は2006.4 FDA承認 Lilly [8%] [23%] [20%] 34,946[21%] 16,833[22%] 333[1%] 1)2001.4 吸入インスリンAIR insulinの共同開発契約。
2)2005.12 parathyroid hormone("PTH")吸入剤AIR parathyroid hormoneの共同開発契約。Amylin [3%] [14%] [1%] 7,882[5%] 5,156[7%] 3,797[10%] 2000.5 exenatideの持続性製剤("exenatide LAR")の共同開発契約。 Genentech 19[-%] 526[1%] 4,495[12%] その他 1,671[1%] 3,165[4%] 1,941[4%] 合計 166,601[100%] 76,126[100%] 39,054[100%]
●Alkermes, Inc. ●Products VIVITROL ●Newsroom - Press Releases FDA Grants Approval for Use of RISPERDAL(R) CONSTA(R) as Both a Monotherapy
and Adjunctive Therapy in the Maintenance Treatment of Bipolar I Disorder[2009.5.18] Exenatide Once Weekly New Drug Application Submitted to FDA for Type 2 Diabetes[2009.5.5] RISPERDAL(R) CONSTA(R) Approved in Japan[2009.4.27] Alkermes Regains Full Commercialization Rights to VIVITROL(R) in US[2008.12.1] - Cephalonとの販売契約を2008.12.1解消。 FDA Approves New Injection Site for RISPERDAL(R) CONSTA(R) for Schizophrenia Treatment[2008.10.9] - 腕の筋注を承認 Supplemental New Drug Application for RISPERDAL(R) CONSTA(R) Submitted to the FDA for the Treatment of Bipolar Disorder[2008.7.24] Supplemental New Drug Application for RISPERDAL(R) CONSTA(R) Submitted to
the FDA for the Treatment of Frequently Relapsing Bipolar Disorder[2008.4.14] FDA Approves New Dose of RISPERDAL(R) CONSTA(R) for Schizophrenia Treatment[2007.4.13] - 12.5 mg用量の認可。 RISPERDAL CONSTAは2003年承認済み(25 mg, 37.5 mg and 50 mg)。 Alkermes Submits Marketing Authorization Application for Vivitrol(R) in the United Kingdom and Germany[2007.4.2] Alkermes Announces Submission of New Drug Application for RISPERDAL(R) CONSTA(R) in Japan[2006.12.20] - ヤンセン社日本でRISPERDAL(R) CONSTA(R) ((risperidone) long-acting injection を申請。本剤はAlkermes社のMedisorb(R)技術使用。 VIVITROL(TM), the First, Once-Monthly Injectable Medication for Alcohol Dependence Now Available in the United States[2006.6.13] - 最初で唯一の１ヵ月１回投与のアルコール依存症治療薬。 米国では1800万人がアルコール依存症でうち220万人が要治療。75%が再発。 Alkermes and Cephalon Receive FDA Approval of Vivitrol(TM) for the Treatment of Alcohol Dependence[2006.4.13] - AlkermesはCephalonに米国での販売権をライセンスし承認時$110 MILLIONのマイルストーンを受け取る契約を 2005.6に締結。 ●Investor Relations ★SEC Filings 10-K Annual[2009.5.28] - [pdf] 10-K Annual[2008.5.30] - [pdf] 10-K Annual[2007.6.14] - [pdf] 10-K Annual[2006.6.14] - [pdf]
■Allergan
http://www.allergan.com/ ●会社決算●事業別
($Million) 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 備考 製品売上高 4,819.6(+8.4) 4,447.6 4,339.7 3,879.0 3,010.1 2,319.2 2,045.6 1,755.4 1,385.0 1,142.1 992.1 うち医薬 3,973.4(+7.9) 3,683.8 3,502.3 3,105.0 2,272.8 1,945.6 1,672.7 1,357.2 1,142.1 992.1 うち医療用具 846.2(+10.8) 763.8 837.4 774.0 46.4 100.0 82.7 27.8 - - 主に契約収入 その他収入 99.8 56.0 63.7 59.9 53.2 23.4 13.3 9.4 研究サービス収入 - - - - - - - 16.0 総収入 計 4,919.4 4,503.6 4,403.4 3,938.9 3,063.3 2,342.6 2,058.9 1,780.8 営業利益 258.6 928.0 796.1 719.4 (3.2) 570.9 527.4
旧1,658.9(23.7)
旧1,435.11,163.3 944.0 794.4 経常利益 170.8 848.5 787..2 687.7 (19.5) 599.2
旧570.9532.1
旧527.4(52.5)
旧-23.7129.0 242.1 研究開発費 804.6 706.0 797.9 718.1 1,055.5 388.3 342.9 762.6 233.1 227.5 165.7 純利益 4.9 623.8 578..6 499.3 (127.4) 403.9 377.1 -52.5 75.2 224.9 215.1 国際売上比率 37.4% 34.6% 34.8% 34.3% 32.6% 32.5% 30.9% 29.6% 29.4% 従業員数 9,200 8,740 7,886 5,055 5,030 *註) Botox (2002) Cosmetic 40%を占める from Allergan Reports Fourth Quarter Operating Results[2004.1.28] Allergan Reports Year End Operating Results[2003.1.29]
($Million) 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 備考 ■医薬品 /Specialty Pharmaceuticals Segment Product ●眼科用薬 2,262.0(+7.7%) 2,100.6 2,009.1 1,776.5 1,530.6 1,321.7 1137.1(+13.8) 999.5(+20.8) 827.3 753.7 683.9 576.2 510.1 Alphagan 401.6(-3.1) 414.5 398.1(+) 341.4(+15.4) 295.9 277.2(+3.1) 268.9(-6.2) 286.8(+15.4) 248.5(+1) 250.9(+8.3) 231.6(+36.9) ? ? Brimonidine Tartrate 緑内障 Lumigan 526.7(+15.4) 456.5 426.2 391.7(+19.6) 327.5 267.6(+14.9) 232.9(+28.5) 181.3(+47.4) 123.0 35.4 - - - Bimatoprost 眼科用緑内障 他の緑内障薬 14.8 15.3(-6.5) 16.3 18.0(-5.9) 19.1(-15.9) 22.7(-7.7) 24.6 Latisse 81.8(+11.0) 73.7 - - - - - - - - - - [Bimatoprost]まつげ美容液（まつ毛育毛剤）FDA承認2008.12.26、米国発売2009.1 Restasis 620.5(+18.7) 522.9 444.0 344.5(+27.5) 270.2 190.9(+91.2) 99.8(+160.6) 38.3(-) - - - - - cyclosporine/ドライアイ ●皮膚科用薬 229.5(+10.3) 208.0 113.7 110.7 125.7 120.2 103.4(-5.4) 109.3(+21.2) 90.2 78.9 68.7 76.6 60.6 Tazorac/Avage - - 77.2(-3.4) 79.9(-12.4) 91.2 86.9(+15.7) 75.1(-6.5) 80.3(+29.3) 62.1 45.4(+39.5) 32.7(+57.2) - - tazarotene ●Botox 1,419.4(+8.4) 1,309.6 1,310.9 1,211.8 982.2 830.9 705.1(+25.0) 563.9(+28.2) 439.7 309.5(+29.2%) 239.5(+39) 175.8 125.3 botulinum toxin A ●泌尿器用薬 62.5(-4.7) 65.6 68.6 6.0 - Sanctura 62.5(-4.7) 65.6 68.2 4.9 - [trospium] ●その他 - - - - - 46.4 100.0(+20.9) 82.7(+197.5) 27.0 主にコンタクトレンズ 医薬品合計 3,973.4(+7.9) 3,683.8 3,502..3 3,105.0 2,638.5 2,319.2 2045.6(+16.5) 1755.4(+26.7) 1385.0 1142.1 992.1 828.6 716 ■医療機器 /Medical Devices Segment Product 胸部エステ 319.1(+11.0) 287.5 310.0 298.4 177.2 - 肥満症用品 243.3(-5.8) 258.2 296.0 270.1 142.3 - 顔エステ 283.8(+30.1) 218.1 231.4 202.8 52.1 - その他 - - - 2.7 - - 医療機器 計 846.2(+10.8) 763.8 837.4 774.0 371.6 -
ボツリヌス毒素 [2010] In 2008, the FDA announced in an “Early Communication” its review of certain adverse events following the use of botulinum toxins, including Botox® and Botox® Cosmetic. In 2009, simultaneously with its approval of Dysport™ , the FDA announced the completion of its review and has requested that we adopt a REMS program equivalent to the REMS program required for Dysport™ . In 2009, the FDA approved our REMS program for Botox® , which addresses the risks related to botulinum toxin spread beyond the injection site and the lack of botulinum toxin interchangeability. In the second quarter of 2010, the FDA requested that we submit an update to the Botox® Medication Guide to include the chronic migraine indication, updated REMS to include a physician training plan for chronic migraine, and a proposed physician communication, including a draft “dear healthcare practitioner” letter announcing the chronic migraine indication and providing information on the updated REMS. In the fourth quarter of 2010, the FDA approved Botox® for the prophylactic treatment of headaches in adults with chronic migraine. We cannot assure you that any other compounds or products that we are developing for commercialization will be approved by the FDA or foreign regulatory bodies for marketing or that we will be able to commercialize them on terms that will be profitable, or at all. If any of our products cannot be successfully or timely commercialized or our direct-to-consumer advertising materials fail to be approved by the FDA, our operating results could be materially adversely affected.
Total sales of Botox increased in 2010 compared to 2009 due to an increase in sales of Botox® for both cosmetic and therapeutic use in all of our principal geographic markets. We believe sales of Botox , primarily Botox® Cosmetic, were negatively impacted in 2010 by the introduction of a competitive product that was launched in the United States in June 2009. Based on internal information and assumptions, we estimate in 2010 that Botox® therapeutic sales accounted for approximately 51% of total consolidated Botox sales and grew at a rate of approximately 6% compared to 2009. In 2010, Botox® Cosmetic sales accounted for approximately 49% of total consolidated Botox sales and increased by approximately 11% compared to 2009. We believe our worldwide market share for neuromodulators, including Botox® , was approximately 77% in the third quarter of 2010, the last quarter for which market data is available.
Our neuromodulator product, Botox® (onabotulinumtoxinA), has a long-established safety profile and has been approved by the FDA for more than 20 years to treat a variety of therapeutic conditions, as well as for aesthetic use since 2002. In 2010, therapeutic uses accounted for approximately 51% and aesthetic uses for approximately 49% of total sales. With more than 2,000 publications on Botox® and Botox® Cosmetic in scientific and medical journals, results of approximately 50 randomized, placebo-controlled clinical trials involving more than 11,000 patients, Botox® is a widely researched medicine with more than 100 potential therapeutic and aesthetic uses reported in the medical literature. Over 18 million treatment sessions have been recorded with Botox® and Botox® Cosmetic in the United States alone over the past 16 years (1994-2009). Marketed as Botox® , Botox® Cosmetic, Vistabel® , Vistabex® or Botox® Vista® depending on the indication and country of approval, the product is currently approved in approximately 80 countries for up to 21 unique indications. In 2009, following the approval of a competitor product, Dysport™ in the United States, we adopted a Risk Evaluation and Mitigation Strategies program, or REMS, including a boxed warning about the potential spread of botulinum toxins from the site of injection and the lack of interchangeability among botulinum toxin products. Sales of Botox® represented approximately 29%, 29% and 30% of our total consolidated product net sales in 2010, 2009 and 2008, respectively. Botox® has been primarily used therapeutically for the treatment of certain neuromuscular disorders which are characterized by involuntary muscle contractions or spasms as well as upper limb spasticity. In the fourth quarter of 2010, the FDA approved Botox® for the prophylactic treatment of headaches in adults with chronic migraine. The approved therapeutic indications for Botox® in the United States are as follows:
kﾎ blepharospasm, the uncontrollable contraction of the eyelid muscles which can force the eye closed and result in functional blindness;
kﾎ strabismus, or misalignment of the eyes, in people 12 years of age and over;
kﾎ cervical dystonia, or sustained contractions or spasms of muscles in the shoulders or neck in adults, along with associated neck pain;
kﾎ severe primary axillary hyperhidrosis (underarm sweating) that is inadequately managed with topical agents;
kﾎ the treatment of increased muscle stiffness in the elbow, wrist and fingers in adults with upper limb spasticity; and
kﾎ the prophylactic (preventative) treatment of headaches in adults with chronic migraine.In many countries outside of the United States, Botox® is approved for treating hemifacial spasm, spasticity associated with pediatric cerebral palsy and upper limb spasticity in post-stroke patients. We are currently in development for Botox® in the United States and Europe for new indications, including lower limb spasticity, neurogenic overactive bladder, idiopathic overactive bladder and benign prostatic hyperplasia.
In the third quarter of 2010, we received approval for Botox® for the prophylactic treatment of headaches in adults with chronic migraine in the United Kingdom. In 2009, we submitted regulatory files for the use of Botox® to treat chronic migraine in France, Switzerland and Canada and are currently seeking approval in the European Union. In the fourth quarter of 2010, we filed a supplemental Biologics License Application, or sBLA, with the FDA for the use of Botox® in the treatment of urinary incontinence due to neurogenic detrusor overactivity resulting from neurogenic bladder and we are currently seeking approval in the European Union and Canada. In 2010, we completed enrollment in our Phase III clinical trials for the use of Botox® to treat idiopathic overactive bladder. In 2005, we initiated Phase II clinical trials outside the United States for the use of Botox® to treat benign prostatic hyperplasia. In 2009, we filed an Investigational New Drug Application with the FDA relating to the use of Botox® to treat benign prostatic hyperplasia.
Botox® Cosmetic
The FDA approved Botox® Cosmetic in 2002 for the temporary improvement in the appearance of moderate to severe glabellar lines in adult men and women age 65 or younger. Referred to as Botox® , Botox® Cosmetic, Vistabel , Vistabex or Botox® Vista , depending on the country of approval, this product is administered in small injections to temporarily reduce the muscle activity that causes the formation of glabellar lines between the eyebrows that often develop during the aging process. Currently, more than 60 countries have approved facial aesthetic indications for Botox® , Botox® Cosmetic, Vistabel® , Vistabex® or Botox® Vista® . In Australia, New Zealand, Canada and certain countries in East Asia and Latin America, we have regulatory approvals for upper facial lines, including crow’s feet. Since we have launched Botox® Cosmetic, we have conducted comprehensive direct-to-consumer marketing campaigns in the United States. We continue to sponsor aesthetic specialty physician training in approved countries to further expand the base of qualified physicians using Botox® , Botox® Cosmetic, Vistabel® , Vistabex® or Botox® Vista® .
In 2005, we entered into a long-term arrangement with GlaxoSmithKline, or GSK, under which GSK agreed to develop and promote Botox® in Japan and China and we agreed to co-promote GSK’s products Imitrex STATdose System® (sumatriptan succinate) and Amerge® (naratriptan hydrochloride) in the United States until the third quarter of 2010. In the first quarter of 2010, we reacquired the rights from GSK to develop and sell Botox® in Japan and China for all current and future cosmetic indications. GSK retains the rights granted under the long-term arrangement to develop and sell Botox® in Japan and China for all current and future therapeutic indications. In 2009, Botox® was approved in Japan for the additional indications of glabellar lines and equinus foot due to lower limb spasticity in juvenile cerebral palsy patients and was launched in Japan for these indications with the glabellar lines indication marketed as Botox® Vista® . Botox® was also approved for the treatment of glabellar lines in China in 2009. In the fourth quarter of 2010, we received approval of Botox® in Japan for the treatment of upper and lower limb spasticity.
Competition
Botox® was the only neuromodulator approved by the FDA until 2000, when the FDA approved Myobloc® (rimabotulinumtoxinB), a neuromodulator formerly marketed by Elan Pharmaceuticals and Solstice Neurosciences Inc. and marketed by US Worldmeds since 2010. In 2009, the FDA approved Dysport™ (abobotulinumtoxinA) for the treatment of cervical dystonia and glabellar lines, which is marketed by Ipsen Ltd., or Ipsen, and Medicis Pharmaceutical Corporation, or Medicis, respectively. The approved package for Dysport™ included a boxed warning regarding the symptoms associated with the spread of botulinum toxin beyond the injection site. Additionally, the FDA approved Ipsen’s and Medicis’ REMS program, which addresses the lack of interchangeability of botulinum toxin products and the risks associated with the spread of botulinum toxin beyond the injection site. Ipsen has marketed Dysport for therapeutic indications in Europe since 1991, prior to our European commercialization of Botox® in 1992. In 2006, Ipsen received marketing authorization for a cosmetic indication for Dysport in Germany. In 2007, Ipsen granted Galderma, a joint venture between Nestle and L’OrAmal Group, an exclusive development and marketing license for Dysport™ for cosmetic indications in the European Union, Russia, Eastern Europe and the Middle East, and first rights of negotiation for other countries around the world, except the United States, Canada and Japan. In 2008, Galderma became Ipsen’s sole distributor for Dysport™ in Brazil, Argentina and Paraguay. In 2009, the health authorities of 15 European Union countries approved Dysport™ for glabellar lines under the trade name Azzalure™ . In the fourth quarter of 2010, Galderma announced its plan to acquire Q-Med A.B., a Swedish company that markets several products for various therapeutic areas derived from hyaluronic acid, including Restylane® and Perlane™ dermal fillers.
In addition, Merz Pharmaceuticals’, or Merz’s, botulinum toxin product Xeomin® , is currently approved for therapeutic indications in Germany and several other countries in the European Union. Xeomin® was approved by the FDA in the third quarter of 2010 for cervical dystonia and blepharospasm in adults previously treated with Botox® . Merz is currently pursuing FDA approval of Xeomin® for cosmetic use in the United States. In 2009, Merz received approval of Bocouture® (rebranded from Xeomin® ) for glabellar lines in Germany. In 2010, Bocouture® was approved in significant markets within the European Union. Xeomin® is also approved for glabellar lines in Argentina and Mexico. In the first quarter of 2010, Merz acquired Bioform Medical Inc., or Bioform, a California-based company that markets Radiesse® , a calcium hydroxylapatite filler. Merz also previously acquired rights from Anteis S.A., a Swiss company, to market Belotero , a hyaluronic acid filler, in certain European markets, the United States and Canada. The FDA accepted Merz’s registration file for Belotero in 2009.
Mentor Worldwide LLC, a division of Johnson & Johnson, or Mentor, is conducting clinical trials for a competing neuromodulator in the United States which Mentor has indicated that it expects to be approved in 2012 or beyond. A Korean botulinum toxin, Meditoxin® , was approved for sale in Korea in 2006. The company, Medy-Tox Inc., received exportation approval from Korean authorities in early 2005 to ship their product under the trade name Neuronox® . Neuronox is marketed in Hong Kong, India and Thailand. Meditoxin® is approved in approximately seven South American countries, including Brazil and Columbia, under various trade names.
In addition, we are aware of competing neuromodulators currently being developed and commercialized in Asia, Europe, South America and other markets. A Chinese entity, Lanzhou Biological Institute, received approval to market a botulinum toxin in China in 1997 under the tradename HengLi, and has launched its botulinum toxin product in other lightly regulated markets in Asia, South America and Central America under several trade names. These lightly regulated markets may not require adherence to the FDA’s current Good Manufacturing Practice regulations, or cGMPs, or the regulatory requirements of the European Medical Evaluation Agency or other regulatory agencies in countries that are members of the Organization for Economic Cooperation and Development. While these products are unlikely to meet stringent U.S. regulatory standards, the companies operating in these markets may be able to produce products at a lower cost than we can.
Our sales of Botox® could be materially and negatively impacted by this competition or competition from other companies that might obtain FDA approval or approval from other regulatory authorities to market a neuromodulator.
緑内障 [2010] The largest segment of the market for ophthalmic prescription drugs is for the treatment of glaucoma, a sight-threatening disease typically characterized by elevated intraocular pressure leading to optic nerve damage. Glaucoma is currently the world’s second leading cause of blindness, and we estimate that over 70 million people worldwide have glaucoma. According to IMS Health Incorporated, our products for the treatment of glaucoma, including Lumigan® (bimatoprost ophthalmic solution) 0.03%, Lumigan® 0.01%, Ganfort™ (bimatoprost/timolol maleate ophthalmic solution), Alphagan® (brimonidine tartrate ophthalmic solution) 0.2%, or Alphagan® , Alphagan® P 0.15%, Alphagan® P 0.1% and Combigan® (brimonidine tartrate/timolol maleate ophthalmic solution) 0.2%/0.5%, captured approximately 26.2% of worldwide market sales in their product categories for first nine months of 2010.
[2008] 当社製品はLumigan(R)(bimatoprost ophthalmic solution) 0.03%, or Lumigan(R), Alphagan(R)(brimonidine tartrate ophthalmic solution) 0.2%, or Alphagan(R), Alphagan(R)P (brimonidine tartrate ophthalmic solution) 0.15%, or Alphagan(R)P, Alphagan(R)P 0.1% (brimonidine tartrate ophthalmic solution)0.1%, or Alphagan(R)P 0.1%, Combigan TM (brimonidine tartrate/timolol maleate ophthalmic solution) 0.2%/0.5%, or Combigan TM and Ganfort(R)(bimatoprost/timolol maleate ophthalmic solution)。 2007年1-9月世界シェア18%
Lumigan 緑内障 (bimatoprost ophthalmic solution) 0.03%, [2010] Lumigan® 0.03% and Lumigan® 0.01% are topical treatments indicated for the reduction of elevated intraocular pressure in patients with glaucoma or ocular hypertension. Lumigan 0.01% is an improved reformulation of Lumigan® 0.03%. We currently sell Lumigan® 0.01% and Lumigan® 0.03% in the United States and over 75 countries worldwide and, together, they are our second best selling eye care products.
According to IMS Health Incorporated, Lumigan® 0.01% and Lumigan® 0.03% were amongst the best selling glaucoma products in the world for the first nine months of 2010. In 2002, the European Commission approved Lumigan® 0.03%. In 2004, the European Union’s Committee for Proprietary Medicinal Products approved Lumigan® 0.03% as a first-line therapy for the reduction of elevated intraocular pressure in chronic open-angle glaucoma and ocular hypertension. In 2006, the U.S. Food and Drug Administration, or the FDA, approved Lumigan® 0.03% as a first-line therapy. We are party to an exclusive licensing agreement with Senju Pharmaceutical Co., Ltd., or Senju, under which Senju became responsible for the development and commercialization of Lumigan® 0.03% in Japan. In 2009, Senju received approval of Lumigan® 0.03% in Japan. Also in 2009, Lumigan® 0.01% was approved by Health Canada. In the first quarter of 2010, the European Commission granted a Marketing Authorization for Lumigan® 0.01% in the European Union member states. During the third quarter of 2010, the FDA approved Lumigan 0.01% as a first-line therapy indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. In 2006, we received a license from the European Commission to market Ganfort&trade in the European Union. Ganfort™ is now sold in over 37 countries outside the United States. Combined sales of Lumigan® 0.03%, Lumigan® 0.01% and Ganfort™ represented approximately 11%, 10% and 10% of our total consolidated product net sales in 2010, 2009 and 2008, respectively.
[2008] ７０ヵ国で販売、2007年1-9月世界シェア第３位。 2002.3 EU承認。 2004.1 EU-CHMPはfirst-line therapyとして承認。 米国FDAも2006.6 first-line therapyとして承認。 2004.5 千寿製薬にライセンス、これは2007.6に日本で申請された。Ganfort&trade 緑内障 (bimatoprost/timolol maleate ophthalmic solution) [2010] [2008] In November 2003, we filed a New Drug Application with the FDA for Ganfort(R), a Lumigan(R)and timolol combination designed to treat glaucoma or ocular hypertension. In August 2004, we announced that the FDA issued an approvable letter for Ganfort(R), setting out the conditions, including additional clinical investigation, that we must meet in order to obtain final FDA approval. In May 2006, we received a license from the European Commission to market Ganfort(R)in the European Union. Combined sales of Lumigan(R)and Ganfort(R)represented approximately 10% of our total consolidated product net sales in 2007. Sales of Lumigan(R)represented approximately 11% of our total consolidated product net sales in 2006 and 12% of our total consolidated product net sales in 2005. The decline in the percentage of our total net sales represented by sales of Lumigan(R)primarily resulted from the significant increase in our net sales as a result of the Inamed acquisition.
Alphagan 緑内障 (brimonidine tartrate ophthalmic solution) [2010] Our third best selling eye care products are the ophthalmic solutions Alphagan® , Alphagan® P 0.15% and Alphagan® P 0.1%. These products lower intraocular pressure by reducing aqueous humor production and increasing uveoscleral outflow. Alphagan® P 0.15% and Alphagan® P 0.1% are improved reformulations of Alphagan containing brimonidine, the active ingredient in Alphagan® , preserved with Purite . We currently market Alphagan® , Alphagan® P 0.15% and Alphagan® P 0.1% in over 70 countries worldwide. In 2002, based on the acceptance of Alphagan® P 0.15%, we discontinued the U.S. distribution of Alphagan . We are party to an exclusive licensing agreement with Senju, under which Senju is responsible for the development and commercialization of Alphagan® and Alphagan® P 0.15% in Japan. The marketing exclusivity period for Alphagan® P 0.1% expired in 2008 and Alphagan® P 0.15 % now faces generic competition in the United States, although we have a number of patents covering the Alphagan® P 0.1% and Alphagan® P 0.15% technology that extend to 2022 in the United States. In 2003, the FDA approved the first generic of Alphagan® . Additionally, a generic form of Alphagan® is sold in a limited number of other countries, including Canada, Mexico, India, Brazil, Colombia, Argentina and in the European Union.
[2008] ７０ヵ国で販売、2007年1-9月世界シェア第５位。 Alphagan(R) Pの2006年発売に伴い、Alphaganは米国販売中止。 2004.5 杏林製薬に独占ライセンス。 杏林は千寿製薬にサブライセンス。 2003.5 Alphaganの初ジェネリックがFDA承認。The marketing exclusivity period for Alphagan(R)P expired in the United States in September 2004 and the marketing exclusivity period for Alphagan(R)P 0.1% will expire in August 2008, although we have a number of patents covering the Alphagan(R)P and Alphagan(R)P 0.1% technology that extend to 2021 in the United States and 2009 in Europe, with corresponding patents pending in Europe. In May 2003, the FDA approved the first generic of Alphagan(R). Additionally, a generic form of Alphagan(R)is sold in a limited number of other countries, including Canada, Mexico, India, Brazil, Colombia and Argentina. See Item 3 of Part I of this report, “Legal Proceedings” and Note 13, “Commitments and Contingencies,” in the notes to the consolidated financial statements listed under Item 15 of Part IV of this report, “Exhibits and Financial Statement Schedules,” for further information regarding litigation involving Alphagan(R). Falcon Pharmaceuticals, Ltd., an affiliate of Alcon Laboratories, Inc., or Alcon, attempted to obtain FDA approval for and to launch a brimonidine product to compete with our Alphagan(R)P product. However, pursuant to a March 2006 settlement with Alcon, Alcon agreed not to sell, offer for sale or distribute its brimonidine product until September 30, 2009, or earlier if specified sales conditions occur. The primary sales condition will have occurred if prescriptions of Alphagan(R)P have been converted to other brimonidine-containing products we market above a specified threshold.Restasis ドライアイ (cyclosporine ophthalmic emulsion) 0.05% [2010] Restasis® (cyclosporine ophthalmic emulsion) 0.05% is the first, and currently the only, prescription therapy for the treatment of chronic dry eye worldwide. Restasis is our best selling eye care product. Chronic dry eye is a painful and irritating condition involving abnormalities and deficiencies in the tear film initiated by a variety of causes. The incidence of chronic dry eye increases markedly with age, after menopause in women and in people with systemic diseases such as SjAzgren’s syndrome and rheumatoid arthritis. Until the approval of Restasis® , physicians used lubricating tears to provide palliative relief of the debilitating symptoms of chronic dry eye. We launched Restasis® in the United States in 2003 under a license from Novartis AG for the ophthalmic use of cyclosporine. During the third quarter of 2010, Health Canada approved Restasis for the treatment of moderate to moderately severe aqueous deficient dry eye disease. Restasis is currently approved in 41 countries.
Our over-the-counter artificial tears products, including the Refresh® and Refresh® Optive™ brands, treat dry eye symptoms including irritation and dryness due to pollution, computer use, aging and other causes. Refresh , launched in 1986, includes a wide range of preserved and non-preserved drops as well as ointments to treat dry eye symptoms. According to IMS Health Incorporated, an independent marketing research firm, our artificial tears products, including the Refresh® and Refresh® Optive™ brands, were again the number one selling artificial tears products worldwide for the first nine months of 2010.
[2008] Novartis AGからライセンスを受け。2003.4 米国発売。現在28ヵ国で販売。 2005.4 NovartisからRestasis関連の全世界の全権をroyalty buy-out(総額$110 million)Prolacria(TM) ドライアイ (diquafosol tetrasodium), or Prolacria(TM) [2008] 2001.6 Inspire Pharmaceuticals, Incから独占開発権を取得。InspireにRestasisと Prolacriaの販売を認めるのと交換。 2003.12 FDAはapprovable letterを発行し追加臨床試験を要求。 2005.2 Inspireは primary endpointでの効果証明失敗を発表。その後secondary endpointsでの試験に基づき 2005Q2に再申請し、2005.12に２番目のapprovable letter受領。Zymar 抗菌剤 (gatifloxacin ophthalmic solution) 0.3% from Kyorin Pharmaceutical Co. Ltd [2010] Our leading anti-infective is Zymar® (gatifloxacin ophthalmic solution) 0.3%, which we license from Kyorin Pharmaceutical Co., Ltd. and have worldwide ophthalmic commercial rights excluding Japan, Korea, Taiwan and certain other countries in Asia and Europe. We launched Zymar® in the United States in 2003. Zymar® is a fourth-generation fluoroquinolone for the treatment of bacterial conjunctivitis and is currently approved in 33 countries. Laboratory studies have shown that Zymar® kills the most common bacteria that cause eye infections as well as specific resistant bacteria. During the second quarter of 2010, we received FDA approval of Zymaxid® (gatifloxacin ophthalmic solution) 0.5%, our next-generation anti-infective product indicated for the treatment of bacterial conjunctivitis. In February 2011, we announced the discontinuation of Zymar® due to strong physician acceptance of Zymaxid® with its increased concentration.
[2008] アジアを除く全世界の権利獲得。第四世代の抗菌剤で29ヵ国で承認。 米国では2003.4発売。2007年は米国で眼科感染症で２番目の処方件数。 金額では世界第３位、米国第二位。[2010]
●Allergan ■Investors ●Earnings Releases Q4 Allergan Reports Fourth Quarter 2010 Operating Results[2011.1] Q4 Allergan Reports Fourth Quarter 2009 Operating Results [2010.1 2008 Q4 Allergan Reports Fourth Quarter Operating Results [2009.1] 2007 Q4 Allergan Reports Fourth Quarter Operating Results[2008.1.30] ●Financial Reports 10-K Annual Report[2011.3.1] - [pdf] 10-K Annual Report[2010.2.26] - [pdf] 2009 Annual Report 10-K Annual Report[2009.2.27] - [pdf] 2008 Annual Report 10-K Annual Report[2008.2.28] - [pdf,188p] 2007 Annual Report - [pdf,16p] ●Products ●Press Releases
●アラガン株式会社 ●日本 2002年7月1日付をもちまして、アラガン株式会社は、医薬品事業を取り扱う「アラガン株式 会社」と眼科医療器具及びコンタクトレンズケア事業を取り扱う「エイエムオー・ジャパン 株式会社」の2社に分割いたしました。 ボツリヌストキシン療法研究会：眼瞼・顔面けいれん／痙性斜頸のページ -http://www.btx-a.net/
■Allos Therapeutics, Inc
(Nasdaq: ALTH)headquartered in Westminster, Colorado 1992.09.01 HemoTech Sciences, Incとして設立。 1994.10.19 Allos Therapeutics, Incに社名変更 2000年に株式公開 ●会社決算
($ 000) 2009 2008 2007 2006 2005 売上高 3,585 - - - - 営業利益 (74,010) (53,639) (42,664) (32,128) (21,905) 経常利益 (73,630) (51,730) (39,370) (30,212) (20,137) 当期純利益 (73,553) (51,730) (39,370) (30,212) 20,137 研究開発費 32,618 30,595 22,992 16,606 12,481 従業員数[連結] 170
●FOLOTYNmV (pralatrexate injection) PTCL治療薬 【2009】We are currently focused on the development and commercialization of FOLOTYNmV (pralatrexate injection). FOLOTYN is a targeted antifolate inhibitor designed to accumulate preferentially in cancer cells. FOLOTYN targets the inhibition of dihydrofolate reductase, or DHFR, an enzyme critical in the folate pathway, thereby interfering with DNA and RNA synthesis and triggering cancer cell death. FOLOTYN can be delivered as a single agent, for which we currently have approval for the treatment of patients with relapsed or refractory peripheral T.cell lymphoma, or PTCL, and has the potential to be used in combination therapy regimens. We believe that FOLOTYN's unique mechanism of action offers us the ability to target the drug for development in a variety of hematological malignancies and solid tumor indications. We currently retain exclusive worldwide commercial rights to FOLOTYN for all indications. We may also seek to grow our product portfolio through product acquisition and in.licensing efforts. On September 24, 2009, the U.S. Food and Drug Administration, or FDA, granted accelerated approval of FOLOTYN for use as a single agent for the treatment of patients with relapsed or refractory PTCL. This approval was based on overall response rate from our pivotal PROPEL trial. Clinical benefit such as improvement in progression.free survival or overall survival has not been demonstrated. FOLOTYN represents our first drug approved for marketing in the United States. FOLOTYN is the first and only drug approved by the FDA for this indication and represents a new treatment option for patients with relapsed or refractory PTCL. In connection with the accelerated approval, we are required to conduct several post.approval studies. We began making FOLOTYN available for commercial sale in the United States on October 5, 2009 and commenced our commercial launch in January 2010 with approximately 50 sales specialists.
FOLOTYN is a targeted antifolate inhibitor designed to accumulate preferentially in cancer cells. Based on preclinical studies, we believe that FOLOTYN selectively enters cells expressing RFC.1, a protein that is over expressed on cancer cells compared to normal cells. Once inside cancer cells, FOLOTYN is efficiently polyglutamylated, which makes it less susceptible to efflux.based drug resistance and leads to high intracellular drug retention. Inside the cell, FOLOTYN targets the inhibition of DHFR, an enzyme critical in the folate pathway, thereby interfering with DNA and RNA synthesis and triggering cancer cell death.
The antimetabolites, including antifolates such as FOLOTYN, are a group of low.molecular weight compounds that exert their effect by virtue of their structural or functional similarity to naturally occurring molecules involved in DNA synthesis. Because the cell mistakes them for a normal metabolite, the antimetabolites either inhibit critical enzymes involved in DNA synthesis or become incorporated into the nucleic acid, producing incorrect codes. Both mechanisms result in inhibition of DNA synthesis and ultimately, cell death. Because of their primary effect on DNA synthesis, the antimetabolites are most effective against actively dividing cells and are largely cell.cycle phase specific. There are three classes of antimetabolites; purine analogs, pyrimidine analogs and folic acid analogs, also termed antifolates. FOLOTYN is a folic acid analog.
The selectivity of antifolates for tumor cells involves their conversion to a polyglutamated form by the enzyme folypolyglutamyl synthetase. Polyglutamation is a time. and concentration.dependent process that occurs in tumor cells, and to a lesser extent, normal tissue. The selective activity of the folic acid analogs in malignant cells versus normal cells likely is due to the relative difference in polyglutamate formation. Polyglutamated metabolites have prolonged intracellular half.life, increased duration of drug action and are potent inhibitors of several folate.dependent enzymes, including DHFR.
We believe that the resistance of malignant cells to the effects of the folic acid analogs may, in part, be due to impaired polyglutamation. We believe the improved antitumor effects of FOLOTYN in comparison to methotrexate, as observed in preclinical studies, is likely due to the more effective uptake and transport of FOLOTYN into the cell followed by the greater accumulation of FOLOTYN and its metabolites within the tumor cell through the formation of the polyglutamated derivatives.
Competition
There are currently no FDA.approved drugs other than FOLOTYN for the treatment of patients with relapsed or refractory PTCL. However, we are aware of multiple investigational agents that are currently being studied in clinical trials for T.cell lymphoma, including romidepsin and belinostat, which, if successful, may compete with FOLOTYN in the United States. In addition, there are many existing approaches used in the treatment of relapsed or refractory PTCL, including combination chemotherapy and single agent regimens, which represent competition for FOLOTYN.
Many companies of all sizes, including a number of large pharmaceutical companies and several biotechnology companies, are developing product candidates that have disease targets similar to those we are pursuing. Some of these competitive product candidates are in clinical trials and others are approved. There are products and technologies currently on the market that will compete directly with FOLOTYN. Universities, governmental agencies and other public and private research organizations also conduct research and may market commercial products on their own or through joint ventures. These companies and institutions also compete with us in recruiting qualified scientific personnel. Many of these entities may have:
●Allos Therapeutics, Inc ●Products FOLOTYN ■Investors ●Financial Reports - SEC Filings 10-K Annual report[2010.3.1] - [pdf] - [doc] - [xls] ●News Allos Therapeutics' Pralatrexate Granted Orphan Medicinal Product Designation for the Treatment of Hodgkin Lymphoma by the European Commission[2010.10.15]
Allos Therapeutics Announces Presentation of Favorable Survival Data from Randomized Phase 2b Study of FOLOTYN(R) in Patients with Advanced Non-Small Cell Lung Cancer[2010.10.11]
Allos Therapeutics Announces FOLOTYN(R) Data Presentation at the 35th ESMO Congress[2010.9.9]
Allos Therapeutics Announces Topline Results from Phase 2b Study of FOLOTYN in Patients with Advanced Non-Small Cell Lung Cancer[2010.7.18]
Allos Therapeutics' Pralatrexate Granted Orphan Medicinal Product Designation for the Treatment of Cutaneous T-Cell Lymphoma by the European Commission[2010.6.17]
Allos Therapeutics' FOLOTYN Shows Activity and Tolerability in Phase 1 Dose Finding Study in Patients with Relapsed or Refractory CTCL[2010.6.11]
Allos Therapeutics Reports New Data Demonstrating that Responses to FOLOTYN are Correlated with Prolonged Survival in Patients with Relapsed or Refractory PTCL[2010.6.5]
Allos Therapeutics' Pralatrexate Granted FDA Orphan Drug Designation for the Treatment of Bladder Cancer[2007.5.18]
Allos Therapeutics Announces an Agreement with Idis for a Named Patient Program for FOLOTYN(TM) (pralatrexate injection)[2009.12.4]
Therapeutics Announces U.S. Availability of FOLOTYN(TM) (pralatrexate injection) for Relapsed or Refractory Peripheral T-Cell Lymphoma[2009.10.5]
Allos Therapeutics' FOLOTYN(TM) First and Only FDA-Approved Therapy for Relapsed or Refractory Peripheral T-cell Lymphoma[2009.9.25]
Allos Therapeutics Announces FDA Advisory Committee Recommends Accelerated Approval of FOLOTYN(TM) (pralatrexate) for the Treatment of Patients with Relapsed or Refractory Peripheral T-cell Lymphoma[2009.9.2]
U.S FDA Grants Pralatrexate Orphan Drug Designation for the Treatment of Patients with Follicular Lymphoma[2008.12.1]
U.S. FDA Grants Pralatrexate Orphan Drug Designation for the Treatment of Patients with Diffuse Large B-Cell Lymphoma[2008.11.24]
[]
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■Almirall Prodesfarma, S.A.
- http://www.almirall.es/ 1943 Laboratorios Almirall, S.A設立 1960 Prodes S.A.設立。 最初の製品Prodesmicina 1964 最初のジエネリックDiazepan Prodes 1979 初の自社開発品clebopride発売。海外ライセンス 1983 Funk S.A. and Berenguer Beneyto S.A.を買収。 1985 局所用消炎剤piketoprofen発売。 1986 Infale S.A買収。 1987 Almirall が国内market leaderとなる。 1990 Farmasimes[スペイン]及び Sintesa[ベルギー]を買収。 gastroprokinetic cinitaprideの発売. 抗ヒスタミン剤 ebastine発売。 国際ライセンス 1991 Prasfarma (Asta Medicaと合弁)をSpainに設立。 1992 抗炎症剤aceclofenac発売。 1993 Probiosの商業活動をポルトガルで開始。 1995 抗炎症剤aceclofenacを南ア, Portugal and Koreaで発売。 1996 aceclofenacを英国発売。 ebastineを日本で発売。 1997 Grupo Farmaceutico Almirall S.A. and the Grupo Prodesfarma. が合併し Almirall Prodesfarma S.A. 2000 片頭痛薬almotriptanが欧州16カ国で相互承認、スペイン発売、FDA承認。 2001 almotriptanの欧州及びEEUU発売。 Prasfarma(癌・病院製品)買収 仏製薬会社Pharmafarm買収 フランスでebastine発売 2002 独・伊・ポルトガルでebastine発売。 2005 PrasfarmaをMerck KGaAに売却、但しスペインでのCampto(irinotecan)の共同販売 権は留保。 ●会社決算（１２月） (Euro million) 2005予 2004 2003 2002 2001 売上高 946 900 886 833 734 うち製品収入 750 738 676 632 583
国内売上 564 559 523 487 439 国外売上 186 179 153 145 144 研究開発費 104 88 85 75 56 従業員数 3227 3196 3200 2843 2605 うち研究開発 500 508 516 508 425 ●研究開発主力分野 喘息、COPD、、乾癬、リウマチ ●開発中の新薬(自社品) LAS 34273 Bronchitis / asthma P-II / III LAS 35201 Bronchitis / asthma P-I / II LAS 37779 Psoriasis P-I FROM Molecules under development ●開発中の新薬(導入品) from News Sativex(R) P3 多発性硬化症 GW Pharmaceuticals (delta-9-tetrahydrocannabinol(THC)& cannabidiol(CBD)) *GW創製、2005.4カナダ承認 blonanserin(AD-5423) P2 統合失調症治療剤 2001.5 大日本住友から全世界ライセンス
●Almirall Prodesfarma, S.A. - http://www.almirall.es/ Strategic alliances - 自社開発品の導出先・国・銘柄名一覧。 導入品目一覧 ●Products ・ almotriptan (片頭痛) ・ ebastine (抗ヒスタミン) －エバステル[大日本住友]発売 ・ aceclofenac (抗炎症) ・ almagate (制酸剤) ・ cinitapride (gastroprocinetic) ・ clebopride (胃潰瘍治療剤gastroprocinetic) －クラスト錠[明治製菓]発売 ・ piketoprofen (抗炎症) ●Communication - Almirall reaches sales figures of 900 million euros in 2004[2005.4.4] - ALMIRALL HAS TAKEN THE STRATEGIC DECISION OF REGISTERING ALMOTRIPTAN IN JAPAN[2004.6.9] -日本での開発 ●R&D Molecules under development
■Alpharma Inc.
Alpharma Inc. (NYSE:ALO), is a multinational pharmaceutical company with global leadership positions in products for humans and animals Grande Commons, 440 U.S. Highway 22 East,3rd Floor, Bridgewater, NJ 08807 908-566-3800With 1,355 employees and revenues of $654 million, Alpharma is active in more than 60 countries around the world. Founded in Norway in 1903, Alpharma is currently positioned for growth atop three strong anchors: pharmaceutical products (KADIAN(R) capsules and the FLECTOR(R) Patch), animal health and active pharmaceutical ingredients. Together, these business units provide operational efficiencies and enable the company to continue to deliver sustainable growth and long-term value.
●Alpharma Inc. -http://www.alpharma.com/pages/default.aspx ●Our Businesses ★KADIAN(R) capsules(morphine sulfate extended-release Capsules) ★FLECTOR(R) Patch(diclofenac epolamine topical patch) ●News Room Alpharma Reports Double-Digit Full Year and Fourth Quarter 2007 Revenue Growth [2008.2.26] The First and Only Anti-Inflammatory Pain Release Patch in the U.S. - FLECTOR(R) Patch - Now Available[2008.1.23] Alpharma Licenses Novel NSAID Topical Pain Drug [2007.9.5] - P3段階にあるketoprofen in Transfersome(R) gelに関して米国独占権を独IDEA AGから獲得した。 IDEA AG は2007.5 Europefor ketoprofen in Transfersome(R) gelの変形関節症の適応で申請した。 Alpharma to Market First Topical NSAID Patch in the U.S.[2007.8.21] - 米国初のNSAIDパッチ剤Flector Patchに関して、Institut Biochimique SAから米国独占販売権を獲得。 欧州ではIBSAが販売している。 1993年でスイスで初承認、以来39ヵ国で承認。
■Alseres Pharmaceuticals, Inc
- http://www.alseres.com/index.asp; (NASDAQ: ALSE) 85 Main Street, Hopkinton, MA 01748 Tel: (508) 497-2360 Fax: (508) 497-9964 創立1992 Boston Life Sciences, Inc. Changes Name to Alseres Pharmaceuticals, Inc.[2007.6.8] ●会社決算■開発中の新薬 /2008.3.13
($ ) 2008 2007 2006 2005 2004 2003 2002 売上高 - - - - - - - 営業費用 18,710,812 18,881,125 26,434,736 11,647,984 10,381,429 7,914,887 10,302,008 当期純利益 (20,847,459) (19,548,348) (26,355,243) (11,501,442) (11,250,877) (8,367,994) (10,993,142) 研究開発費 10,851,844 10,475,158 18,538,186 6,127,486 6,400,132 従業員数[連結] 27 27 27 from Product-Pipeline ★Cethrin(R) -- In January 2007, enrollment was initiated at the 9 mg dosage level in our Phase I/IIa trial of Cethrin at sites in Canada. In June 2007, the Food and Drug Administration, or FDA, authorized an increase in the dose level to 9 mg for sites in the U.S. Each authorized dose is first given to thoracic SCI subjects and then, following review by the Data Safety Monitoring Board, or DSMB, the dose is extended to cervical subjects. In September 2007, the DSMB unanimously authorized expanding the 9 mg dose to include cervical subjects. -- In September 2007, the Company had a preliminary meeting with the European Medicines Agency to review our proposed clinical development plan for CETHRIN. In October 2007, the Company met with the FDA to review the Phase I/IIa results and its CETHRIN clinical development plan. The Company plans to meet with Health Canada in early 2008 for the same purpose. Based on discussions to date with the regulatory authorities and expert advisors, the Company is planning to begin a Phase IIb trial at sites in North America and Europe in the first half of 2008. from Alseres Pharmaceuticals, Inc. Reports Third Quarter 2007 Financial Results and Provides Development Pipeline Update[2007.11.14]
製品 適応 段階 備考 ■Regenerative Therapeutics CNS Cethrin® Acute spinal cord injury P2 2007.1 BioAxone Therapeutic Inc. of Montreal, Canadaから全世界独占開発販売権を獲得。a Rho Inhibitor。 米国では脊髄損傷が毎年11,000件発生し、現在methylprednisoloneの適応外使用が唯一の治療法 Inosine Stroke, SCI 前臨床終了 ALSE-100, etal. Chronic SCI, TBI 研究中 OCULAR Oncomodulin Optic Nerve Injury/
Glaucoma研究中 ALSE-100 Glaucoma/macular degeneration/
retinis pigmentosa研究中 BONE ALSE-100 Bone repair/
osteo-induction前臨床終了 CARDIOVASCULAR ALSE-100, etal. Cardiomyopathy 研究中 ■Molecular Imaging ★ALTROPANE(R)(123I-SPECT) Parkinson's Disease診断 P3終了 誤診率25-35%を改善 Tc-based agents Parkinson's Disease / ADHD 前臨床終了 ■DAT Blocker(Dopamine Transporter Blocker) DAT Blocker Parkinson's Disease 前臨床終了 ３種
●Alseres Pharmaceuticals, Inc ●Product-Pipeline ■Investor Relations ●Financial Information ★SEC Filings 10-K annual report[2009.3.31] 10-K annual report[2008.3.31] 10-K annual report[2007.4.2] ★Annual Reports ●Press Releases Alseres Pharmaceuticals, Inc. Reports Third Quarter 2007 Financial Results and Provides Development Pipeline Update[2007.11.14] Boston Life Sciences, Inc. Changes Name to Alseres Pharmaceuticals, Inc.[2007.6.8] Alseres Pharmaceuticals Concludes Enrollment in the Cethrin(R) Phase I/IIa Clinical Trial in Acute Spinal Cord Injury[2008.1.7] QSV Biologics, Ltd. and, Alseres Pharmaceuticals, Inc., Sign Contract for cGMP Manufacture of Cethrin(R) for Spinal Cord Injury[2007.7.10] Alseres Pharmaceuticals Announces FDA Clearance to Increase Dose Level in Cethrin(R) Phase I/IIa Clinical Trial for Acute Spinal Cord Injury at U.S. Sites[2007.6.27] Boston Life Sciences Acquires Rights to Develop and Commercialize Promising Phase II
Spinal Cord Injury Drug, Cethrin(R), in Exclusive Worldwide License[2007.1.4]
■Altana AG
- http://www.altana.de/root/index.php ALTANA AG completes sale of pharmaceuticals business to Nycomed[2006.12.29] ●決算[連結]●地域別[全体]
(Euro milllion) 2006 2005 2004 2003 2002 2001 2000 売上高 3,867 3,272 2,963 2,735(+5) 2,609 2,308 1,928 医薬事業 2,573 2,365 2,109 1,980 1,861 1,591 1,262 化学事業 1,294 907 854 755 748 717 666 営業利益 676 604 563(+5) 538 経常利益EBT 779 684(+14) 624 580(+10) 526 448 329 純利益 3,872 438 379 345(+6) 324 256 179 研究開発費 495(+6) 465 448 412(+12) 369 285 219 医薬 427 418[17.7%] 410(+8)[19.4%] 376[19.0%] 335 252 190 化学 68 47 38 36 34 33 29 従業員数 13,404 13,276 10,783(+4) 10,402(+6) 9,853 9,122 8,556 医薬 8,920(+1) 8,832 8,200(+6) 7,702 7,504 6,867 6,489 うち研究開発 1,656(+9) 1,514(+18) 1,281 1,052 927 化学 4,484 4,384 2,521 2,634 2,299 2,217 2,036 ●地域別[医薬]
(Euro milllion) 2006 2005 2004 2003 2002 2001 2000 欧州 627 454
旧1,6741,504 うち独 223 142
旧581491 北米 268 156
旧927880 うち米国 243 144
旧796769 中南米 - -
旧327278 極東 297 214
旧285250 その他 102 83
旧5951 合計 1,294 907
旧3,2722,963 ●セグメント別
(Euro milllion) 2006 2005 2004 2003 2002 2001 2000 医薬事業 2,573(+9) 2,365(+12) 2,109(+7) 1,980(+6) 1,861 1,591 1,262 欧州 1,227(+1) 1,219(+16) 1,050(+8) 972(+4) 932 うちドイツ 380(-14) 439(+18) 371(-1) 375(-4) 390 北米 936(+22) 770(+3) 749(+2) 732(+16) 633 うち米国 761(+17) 651(+1) 647(+1) 638 中南米 311(+12) 279(+19) 235(+10) 213(-10) 236 その他 99(+3) 97(+29) 75(+18) 63(+5) 60 * 医薬事業が81%、うち北米が37% ●製品売上高
(Euro milllion) 2006 2005 2004 2003 2002 2001 2000 売上高 3,867 3,272 2,963 2,735(+5) 2,609 2,308 1,928 医薬事業 2,573(+9) 2,365(+12) 2,109(+7) 1,980 1,861 1,591 1,262 治療薬 2,261(+9) 2,071(+13) 1,839(+7) 1,724 1,565 1,275 980 消化器 1,702(+11) 1,536(+12) 1,367(+10) 1,241(+15) 1,083 795 呼吸器 83(+20) 69(+17) 59(-1) 59(+3) 57 53 その他 476 466(+13) 413(-3) 424(-) 425 427 Imaging 108(-1) 108(-) 109(+3) 106 100 91 (OTC) 149(+14) 131(+13) 115(+11) 104 110 129 その他 55(+0) 55(+19) 46(-) 46 86 96 合計 2,573(+9) 2,365(+12) 2,109(+7) 1,980 1,861 1,591 化学事業 1,294(+43) 907 854 755 748 717 666 添加剤・機器
(Additives & Instruments)409(+13) 364 348(+13) 308 304 - - 電気断熱剤
(Electrical Insulation)325(+11) 293 291(+29) 225 223 - - 塗料・シール
(Coatings & Sealants)221(+26) 175 215(-3) 222 221 - - Effect Pigments 339(+13) 75 - - - - - 合計 1,294(+43) 907 854 755 748 717 666 ★造影剤(Bracco S.p.A.と提携,) Imeron & Solutrast - CTの増加で好調 ProHance & MultiHance - Magnetic resonance造影剤(MRI) ★ciclesonide (Alvesco) - 革新的な吸入ステロイド：喘息 (Eur1 Billion予想) [2005] (1990年代初めスペインELMUQUIMICA社買収により取得) 申請済み(2002) --- 英、オーストラリア、カナダ他 (2003) --- サノフィアベンティスが2003.末に米国申請。(契約2002) (2004) --- 帝人が日本で2004.1申請。(契約1998) 承認 --- Australian Health Agencyが2004.2 世界初承認。 発売 (2005.1)--- 英・独発売 2005末１６ヵ国で販売、３４ヵ国承認 点鼻薬：2005.12 FDA申請 by Altana [2004] 承認済み(2004) --- 英2004.4、オーストラリア2004.2、ブラジル・メキシコ2004.8 米国Approvable Letterを2004.10受領 EU相互承認手続き[MRP]2004.12完了 発売 (2005) --- 英国2005.1、ドイツ2005.2 ★roflumilast (Daxas) - COPD治療薬 (Eur1 Billion予想)革新的PDE4阻害剤 [2004] 申請済み(2004) --- EU2004.2 臨床試験(2004) 米国Pfizerは喘息・COPDでP3試験実施、日本の田辺は 喘息でBridging studyを開始。 [2003] ・COPDは"Smoker's lung"として知られ、世界４位の死因。 ・特異的PDE阻害剤で抗炎症作用がある。 COPDと喘息の療法に有効であることを実証した最初の特異的PDE4阻害剤 ・2002年以来Pfizerと共同開発。日本は田辺製薬と共同開発・共同販売 ・RECORD studyを2003.9開始。 有効性・安全性のため。 ・EU申請2004.2 ●パントプラゾール
(Euro milllion) 2006 2005 2004 2003 2002 2001 備考 Pantoprazole 1,551(+14)[69%] 1,361(+12)[57.6%] 1,216[57.6%] 1,113[26.2%] 966 680 (Protozol)潰瘍 Alvesco 18.2 8.1(-) - - - [cicletanide]喘息；発売2005.1 Contrast media 105 106 100 70 Ebrantil(R) 67 66 63 61 [urapidil]降圧剤;α遮断剤 Ferro 29 - 30 33 [ferro polymaltose]鉄剤 Riopan(R) 28 30 33 34 [Magaldrat]制酸剤・胸やけ Facial Topicals - - 26 - Theophylline - - 25 26 Euphyllin/Euphylong Querto(R) - - 24 23 [Carvedilol]from Roche;特許切れ2004 Sanostol(R) - - 20 17 []ビタミン剤 Chromagen - - 16 18 鉄剤＊2003.6 KV Pharmaceuticalsに売却 CroFab(TM) - 29 - 17 蛇毒 * ドイツPantozol, 米国ではProtonix[Wyeth] [年報2005] 1995世界発売以来、現在100ヵ国で販売。 PPI世界市場規模 Euro 14 million(2005) * pantoprazoleのPPI市場シェア20%(2005米国)16%(2003) * 市況(2003) esomeprazoleの発売、及びGeneric登場があった。 しかし堅調な伸び。 しかし数カ国ではomeprazoleの影響あり。 剤型は錠剤(20mg,40mg)、注射剤 * 特許 米国特許が５年間延長し、2010年7末迄に。 欧州は2009年まで。 * 第一製薬と1993.2.22にライセンス契約。 2000.10に契約終了。 Daiichi termination agreement On February 22, 1993, the Company and Daiichi Pharmaceutical Co., Ltd. entered into a licensing agreement pertaining to the development and commercialization of Pantoprazole by Daiichi in Japan. Daiichi terminated the agreement effective October 2000. Under the termination agreement, Daiichi agreed to pay the Company a total of Euro18.4 million in three annual installments as a settlement for termination. These payments are non-refundable and release Daiichi completely from its obligation under the licensing agreement. The first installment, totaling Euro6.1 million was paid during 2000. The second installment, was paid on October 1, 2001. The final installment, is due on October 1, 2002. In 2000, the Company initially recorded only the first installment as other income. The financial statements as of and for the year ended December 31, 2000, have been restated to reflect the entire settlement as other income in the year 2000 as ALTANA has no future obligations or commitments with respect to the termination of the licensing agreements or resulting payments. ●主要特許期限
(Euro milllion) 2006 2005 2004 2003 2002 2001 2000 売上合計 2,882(+4) 2,768(+12) 2,481(+6) 2,350(+17) 2,007 1,326 650 自社売上分 1,551(+14) 1,361(+12) 1,216 1,113 966 680 411 独 226(-23) 292(+40) 210(+9) 193(+6) 182 仏 155(+36) 114(+37) 83 伊 95(+20) 79(+14) 70 スペイン 116(+23) 94(+34) 70 英 38(+13) 34(+56) 22 他の欧州 277(+17) 237(+25) 190 欧州 計 1,030(-2) 1,049
旧757(+11)681 米国 1,429(+5) 1,356(+6) 1,281 カナダ 212(+21) 175(+19) 147 北米 計 1,641(+7) 1,531 1,428(-2) 1,456(+17) 1,247 中南米 64(+21) 52(+11) 48(+3) 46(-11) 52 その他 147(+8) 136(+18) 114(+17) 97(+7) 91 (1)主要国の欧州特許または各国特許 (2)欧州では2016年迄期間延長のためのSPCが認められている。 (3)特許期間延長が５年間迄認められるが、これを反映していない。 *SEC 20-F Annual Report 2005
製品 欧州(1) 米国 日本 ciclesonide(物質) 2011(2) 2013(3) 2011(3) ciclesonide(Key中間体) 2014 2015 2014 ciclesonide(精製工程) 2017 2019 2017 ciclesonide(エアゾール) 2018 2018 2018 ciclesonide(点鼻製剤) 2020 2020 2020 roflumilast(物質) 2014(3) 2015(3) 2014(3) roflumilast(製剤) 2023 2023 2023 soraprazan(物質) 2019(3) 2019(3) 2019(3)
●Altana AG ●Press Release ALTANA AG: Excellent business year 2006[2007.1.26] ALTANA AG completes sale of pharmaceuticals business to Nycomed[2006.12.29] - ■Investor Relations ●Publications Annual Report 2006[pdf,188p] - Interactive Annual Report 2005[pdf,188p] - Interactive --- 医薬35-54; 174p 子会社と持株比率MAJOR CONSOLIDATED COMPANIES SEC-Filing 20-F 2005[pdf,196p] Annual Report 2004[pdf,172p] - Interactive --- 医薬27-44, 開発品目一覧42p; 164p 子会社と持株比率MAJOR CONSOLIDATED COMPANIES SEC-Filing 20-F 2004[pdf,p] Annual Report 2003[pdf,164p] --- 医薬24-39, 開発品目一覧36p; 149p 子会社と持株比率MAJOR CONSOLIDATED COMPANIES SEC-Filing 20-F 2003 Annual Report 2002 Annual Report 2001[pdf, 124p] - Geschaftsbericht 2001 --- 医薬30-, 開発品目一覧36p ●R&D/Products Pharmaceuticals research & development Top ten products
●Altana Pharma AG[旧Byk-Gulden AG] --- Altana AGの製薬部門。 年間売上Euro 1.6 Billion(1860億円)[2001]、従業員総数7500、世界20か国に支社。 ●News March 21, 2003★ALTANA closes 2002 with seventh consecutive record year: ●Products - pantoprazole[要登録] Therapy & Diagnosis - 大した内容はない
●日本
ALTANA Pharma KK,Osaka (J) 100% BYK-Chemie Japan KK, Osaka (J) 100%
■Alza Corporation
- June 22, 2001 J&Jの完全子会社となる。 従業員数3000人以上[米国内のみ] 従って決算は、J&Jで行い、個別決算は非公開。 但し、サイトは存続。●Alza Corporation Annual Report 2000-Financial section[36p]
3p ALZA Corporation 2000 Annual Report[27] Management's Discussion and Analysis of Financial Condition and Results of Operations ●売上高================================== ★SEQUUS Pharmaceuticals, Inc. (Nasdaq: SEQU) 1981 設立 1995 Liposome Technology Inc (HW)からSEQUUS Pharmaceuticals, Inc.に社名変更 1995 .12 Doxil発売。 .12 AMPHOTECに関してSchering-Plough Corpに販売ライセンス 1998 .10 Alzaに吸収合併される。 ALZA To Acquire SEQUUS[1998.10.5] SEQUUS Pharmaceuticals, Inc. ==================================
(Dollars in millions) 2000 1999 1998 備考 ●ALZA Pharmaceuticals Ditropan XL(R) 179.0 86.9(+84) 47.2 [oxybutynin Cl]過活動膀胱;発売1999Q1 Doxil(R)/欧州Caelyx(R) 82.4(+24) 66.2(+37) 48.4 [doxorubicin]卵巣癌 Concerta(TM) 67.9 - - [methylphenidate HCl]ADHD治療薬;発売2000.8 Ethyol(R) 48.4 48.3 32.6 [amifostine];2002.10.1 Medimmuneへ Elmiron(R) 33.7 29.9 23.0 [pentosan polysulfate sodium]間質性膀胱炎；1997.9 IVAXから米加の販売権取得 Mycelex(R) Troche 19.5(-33) 29.2 25.9 [clotrimazole]抗真菌剤; Testoderm TTS(R) line 18.6 20.8 10.0 [testosterone] Other 28.2 42.1 35.9 Total ALZA Pharmaceuticals 477.7 323.4 175.8 ●ALZA Technologies Contract manufacturing 129.5 124.6 113.6 Intersegment 53.4 41.2 22.1 Total ALZA Technologies 182.9 165.8 135.7 Intersegment eliminations (53.4) (41.2) (22.1) Total net sales 607.2 448.0 289.4
●ALZA Corporation --- http://www.alza.com/ ; ●Presse Release Johnson & Johnson Announces Completion of Merger with ALZA Corporation[01.6.22] --- Alzaは、J&Jの完全子会社になった。 会社はそのまま。 Concerta - A success story[12p; Winter 2001] --- - An Interview with Dr. Alejandro Zaffaroni, ALZA's Drug Delivery Visionary - Patterned Drug Delivery Using ALZA's OROS(R) Technology
AMAG Pharmaceuticals, Inc
■AMAG Pharmaceuticals, Inc
- http://www.amagpharma.com/ 貧血治療薬および癌・循環器疾患の造影剤の開発に特化 100 HAYDEN AVENUE. LEXINGTON, MA, 02140; www.advancedmagnetics.com 1981年設立 ●会社決算
($ 000) 2009 2008 2007 2006/10-12 2006/9 2005/9 (製品売上) 16,482 751 1,208 353 1,449 890 (ライセンス収入) 516 959 1,096 222 907 1,281 (ロイヤリティ収入) 180 228 248 44 317 274 売上高 合計 17,178 1,938 2,552 619 2,673 2,445 売上原価 1.013 292 320 287 273 204 研究開発費 36,273 31,716 24,236 6,393 21,294 12,037 販売・管理費 77,829 49,536 20,396 2,197 8,011 3,338 (原価および経費) 115,115 81,544 44,952 8,877 29,578 15,579 経常利益 (94,619) (71,925) (33,894) (7,440) (25,365) (12,715) 当期純利益 (93,351) (71,647) (33,894) (7,440) (25,365) (12,715) 従業員数[連結] 283 Feraheme 15,774 - [Ferumoxytol ] GastroMARK 708(+78) 398 [ferumoxsil]腹部造影 Feridex I.V. - 333 [ferumoxides]肝臓造影剤 その他製品 - 20 製品売上 計 16,482(>+100) 751
●Feraheme(Ferumoxytol) 鉄欠乏性貧血 【2009】On June 30, 2009, Feraheme was approved for marketing in the U.S. by the U.S. Food and Drug Administration, or the FDA, for use as an IV iron replacement therapy for the treatment of iron deficiency anemia, or IDA, in adult patients with chronic kidney disease, or CKD. We market and sell Feraheme through our own commercial organization, consisting of approximately 120 professionals, including an 80.person specialized sales force and account management and reimbursement teams. We sell Feraheme primarily to authorized wholesalers and specialty distributors and began commercial sale of Feraheme in the U.S. in July 2009. In November 2009, the Centers for Medicare & Medicaid Services, or CMS, assigned Feraheme two unique Q.codes, one for the treatment of IDA in end.stage renal disease patients undergoing dialysis and one for the treatment of IDA in non.end.stage renal disease patients. These Q.codes, which are temporary product.specific codes that enable automated processing of Feraheme.related claims, became effective on January 1, 2010.
For the year ended December 31, 2009, we recognized net product sales of Feraheme of $15.8 million, including approximately $1.3 million of the $11.5 million in deferred product revenues we had recorded in the third quarter of 2009. During the third quarter of 2009, shortly after the launch of Feraheme, we implemented a Launch Incentive Program under which certain dialysis organizations purchased Feraheme directly from us. This program provided certain customers with, among other things, discounted pricing and expanded rights of return. As a result, we deferred revenues associated with this program which we will recognize as revenues as the participating organizations utilize their Feraheme inventory. We expect that utilization of the remaining deferred product revenues from the Launch Incentive Program will increase going forward as each Launch Incentive Program customer has begun to use Feraheme.
In December 2009, we submitted draft protocols for two proposed clinical trials to meet our FDA post.approval Pediatric Research Equity Act requirement to support pediatric labeling of Feraheme. In 2010, we intend to initiate these two randomized, active controlled pediatric studies in children with IDA. One study will be in dialysis dependent CKD patients, and the other will be in CKD patients not on dialysis. Each study will assess the safety and efficacy of Feraheme treatment as compared to oral iron in approximately 144 children.
We also plan to advance our Feraheme clinical development program in adults by initiating two Phase III multi.center clinical trials in mid.2010 to assess Feraheme for the treatment of IDA in a broad range of patients, which may include women with abnormal uterine bleeding, or AUB, patients with cancer and gastrointestinal diseases and postpartum women, for whom oral iron is unsatisfactory. One study will assess the efficacy and safety of two doses of 510 milligrams each of Feraheme compared to placebo in a total of approximately 800 patients with IDA. A second study will assess the efficacy and safety of two doses of 510 milligrams each of Feraheme compared to a total dose of 1,000 milligrams of an IV iron sucrose product in a total of approximately 600 patients with IDA. Further, we intend to initiate an open label extension study enrolling patients from the placebo controlled study who will be followed for six months and will be eligible to receive two doses of 510 milligrams each of Feraheme whenever they meet treatment criteria.
We continue to evaluate our strategy for seeking approval for Feraheme as an IV iron replacement therapeutic agent in countries outside of the U.S.
The commercial opportunity for Feraheme as an IV iron replacement therapeutic agent varies from country to country, and in determining which additional markets outside of the U.S. we intend to enter, we are assessing factors such as potential pricing and reimbursement, the role of iron in medical treatment protocols, and the regulatory requirements of each country. We expect to file a Marketing Authorization Application, or MAA, for Feraheme for the treatment of IDA in CKD patients with the European Medicines Agency, or EMEA, in mid.2010. In the fourth quarter of 2009, we received approval from the EMEA for our Pediatric Investigation Plan, which is a prerequisite for the submission of our Feraheme MAA. Our Pediatric Investigation Plan includes the two pediatric studies required to meet our Pediatric Research Equity Act requirement and two additional pediatric studies requested by the EMEA. To further support our MAA, we have initiated a global, randomized, Phase IV multi.center, active controlled trial with approximately 150 adult CKD patients both on dialysis and not on dialysis. This study will assess the safety and efficacy of two doses of 510 milligrams each of Feraheme compared to a total dose of 1,000 milligrams of an IV iron sucrose product.
In December 2009, we filed a New Drug Submission for Feraheme to treat IDA in patients with CKD with the Therapeutic Products Directorate of Health Canada, or Health Canada, the federal authority that regulates pharmaceutical drugs and medical devices for human use in Canada. In February 2010, we received a Screening Deficiency Notice from Health Canada requesting certain clarifications and additional documents. We have submitted our response to Health Canada and believe that all of these items are readily addressable. In addition, in December 2009, our partner in China, 3SBio Inc., or 3SBio, filed an application with the Chinese State Food and Drug Administration, or the SFDA, to obtain approval to begin a registrational clinical trial necessary to file for marketing approval in China. Once approved by the SFDA, 3SBio plans to commence a multi.center randomized efficacy and safety study in China involving approximately 200 CKD patients.
In addition to its use for the treatment of IDA, Feraheme may also be useful as a vascular enhancing agent in magnetic resonance imaging, or MRI. In August 2008, the FDA granted Fast Track designation to Feraheme with respect to its development as a diagnostic agent for vascular.enhanced MRI for the assessment of peripheral arterial disease, or PAD, in patients with CKD. We have enrolled over two.thirds of our 108 patient Phase II study of Feraheme in vascular.enhanced MRI for the detection of clinically significant arterial stenosis or occlusion, or narrowing or blocking of the arteries.
【2009 適応】Feraheme as an IV Iron Replacement Therapeutic Overview
On June 30, 2009, Feraheme was approved for marketing in the U.S. by the FDA for use as an IV iron replacement therapy for the treatment of IDA in adult patients with CKD. In July 2009, we began to market and sell Feraheme in both the dialysis and non.dialysis CKD markets, including to nephrologists, hematologists, dialysis organizations, hospitals and other end.users who treat patients with CKD.
Chronic kidney disease, anemia, and iron deficiency
It has been estimated that approximately 10% to 15% of the U.S. adult population is affected by CKD, a condition generally characterized by damaged kidneys, or a reduction in kidney function below 60% of normal. Anemia, a common condition among CKD patients, is associated with cardiovascular complications, decreased quality of life, hospitalizations, and increased mortality. Anemia develops early during the course of CKD and worsens with advancing kidney disease. Iron deficiency is a common cause of anemia in CKD patients and can result from multiple blood draws, hospitalizations and interventional procedures, gastrointestinal bleeding, or poor nutritional intake. Regardless of the cause of anemia, iron replacement therapy is essential to increase iron stores and raise hemoglobin levels. Iron is also essential for effective treatment with erythropoiesis stimulating agents, or ESAs, which are commonly used in anemic patients to stimulate red blood cell production.
According to an estimate by the United States Renal Data System, approximately 400,000 CKD patients are projected to be on dialysis in the U.S. in 2010. Approximately 90% of these dialysis patients will receive IV iron as part of managing their anemia. In addition, data contained in a 2002 publication in the Journal of the American Society of Nephrology suggests that up to 1.6 million of stage 3 and 4 non.dialysis CKD patients with anemia may be iron deficient and could therefore benefit from receiving IV iron. We believe that less than 10% of these patients are currently being treated with IV iron.
Currently there are two methods used to treat IDA in CKD patients: oral iron supplements and IV iron. Oral iron supplements are often not absorbed well by the gastrointestinal tract and frequently have side effects, such as constipation, diarrhea, and cramping, which can cause patients to stop taking their medication. In addition, it can take an extended time for hemoglobin levels to improve following the initiation of oral iron treatment. Conversely, iron given intravenously allows larger amounts of iron to be provided to patients while avoiding many of the side effects and treatment compliance issues associated with oral iron, and can result in faster rises in hemoglobin levels. The administration of IV iron has been shown to be effective in treating anemia either when used alone or in combination with an ESA. Current U.S. treatment guidelines indicate that treating first with iron alone may delay or reduce the need for ESA therapy.
For IV iron replacement therapy in patients with CKD, the total therapeutic course of iron typically used in clinical practice is 1,000 milligrams, or one gram. Rapid administration of large doses of other IV iron products has been associated with an unfavorable safety profile. As a result, other IV iron products are typically administered as a slow push or a 15 to 60 minute infusion in doses of 100 to 200 milligrams, thus requiring five to ten physician visits and repeated IV access for patients to receive a standard one gram therapeutic course, potentially resulting in considerable burden to both providers and patients. Feraheme is administered as a 510 milligram injection followed by a second 510 milligram injection three to eight days later, each of which can be administered in as fast as 17 seconds at a regular office visit or during dialysis treatment without the use of infusion equipment or prolonged medical intervention.
Feraheme in indications other than CKD
IDA is widely prevalent in many different patient populations, including women with AUB, patients with cancer and gastrointestinal diseases, and postpartum women. We believe that the product characteristics of Feraheme support clinical development in these additional indications, and we are currently in the process of preparing for a global clinical development program for Feraheme in a broad range of patients with IDA, regardless of the underlying cause. We intend to initiate our Phase III program for Feraheme in IDA in mid.2010.
Included among the patient populations we are evaluating for additional indications for Feraheme are women with AUB and cancer patients.
AUB is defined as chronic, heavy, or prolonged uterine bleeding that can result from multiple causes, including uterine abnormalities, blood disorders, pregnancy, intrauterine devices, medications, and heavy menstrual bleeding. Both iron deficiency and IDA are commonly associated with AUB. The prevalence of anemia in AUB patients has been reported to range from 10% to 67%, and the prevalence of iron deficiency in AUB patients has been reported to range from 20% to 50%, depending on patient age and diagnostic criteria. IDA in patients with AUB, regardless of the cause, requires treatment with iron supplementation, either by oral or IV administration.
Anemia is also common in patients with cancer. Depending on the type of cancer, it has been estimated that between 30% and 90% of patients with cancer have anemia. Iron supplementation through both oral and IV administration has an important role in treating anemia in cancer patients. While there may be some differences in the underlying causes of anemia and iron deficiency in cancer patients who are receiving chemotherapy and those who are not, patients in both categories may develop absolute IDA due to blood loss and/or the inadequate intake or absorption of iron. Oral iron has been used to treat IDA in cancer patients, but its efficacy is variable due to inconsistent bioavailability and absorption, the high incidence of gastrointestinal side effects, potential interactions with other treatments and patient noncompliance. IV iron has been shown in small clinical trials to be well tolerated in the cancer patient population in both patients who are receiving chemotherapy and those who are not.
Ferumoxytol as a Diagnostic Agent for Vascular Enhancement in MRI
MRI is a non.invasive method used to visualize normal or abnormal anatomy or pathophysiology in patients in order to diagnose disease and injury.
Imaging agents or biomarkers play an important role in improving the quality of diagnostic images by increasing the contrast between different internal structures or types of tissues in various disease states.
Ferumoxytol is currently in development as an agent for vascular.enhanced MRI because of its ability to increase the magnetic relaxivity of blood, resulting in MRIs with enhanced vascular contrast. When used with the appropriate pulse sequence, ferumoxytol may provide high.quality diagnostic images. In addition to its superparamagnetic properties, ferumoxytol can be administered rapidly as an IV injection at a rate of up to one milliliter per second. It also has a long blood half.life of approximately 15 hours, which may permit repeated imaging of the same or different body regions. These features of ferumoxytol may make it useful as an MRI biomarker in vascular disorders.
The initial focus of our clinical development of ferumoxytol as an imaging agent has been in patients with PAD for the detection of clinically significant arterial stenosis or occlusion. PAD is a manifestation of atherosclerotic cardiovascular disease and can occur when plaque builds up on the inside wall of the arteries that carry blood from the heart to the head, internal organs and limbs causing the arteries to narrow, which can reduce or block blood flow. Symptomatic PAD is associated with decreased quality of life, and whether symptomatic or asymptomatic, PAD is associated with an increased risk of cardiovascular and cerebrovascular problems, and cardiovascular mortality.
The prevalence of PAD in the U.S. is estimated to be approximately 8 million adults, affecting up to 20% of individuals 65 years of age and older. The prevalence of PAD increases with age, diabetes, CKD, hypertension and smoking, as does the presence of known atherosclerosis in other parts of the body.
In the U.S., cardiovascular disease is a common cause of morbidity and mortality, with a prevalence of approximately one in three adults. Additionally, cardiovascular disease is the leading cause of death, accounting for approximately 35% of all deaths in 2005.
Both the diagnosis and clinical management of PAD and cardiovascular disease often require the accurate assessment of vascular anatomy, and therefore, there is an important medical need for the availability of safe and effective techniques for invasive and/or non.invasive imaging modalities in these patient populations. High.resolution imaging, including digital subtraction angiography, contrast.enhanced computed tomography, and contrast.enhanced magnetic resonance angiography all provide the depiction of vascular anatomy required for consideration of endovascular or surgical intervention. However, there are important side effects of these techniques that seriously impact the appropriate evaluation of patients. There is a well.known risk of kidney damage associated with the administration of certain contrast agents for computed tomography, digital subtraction angiography, and X.ray angiography. Several currently approved contrast agents used for MRI in the U.S. are gadolinium.based and are associated with rare but severe adverse events in patients with CKD. In September 2007, the FDA issued a "Black Box" warning for all gadolinium.based contrast agents in certain patients due to these agents' potential association with Nephrogenic Systemic Fibrosis, or NSF. NSF is a condition that so far has only occurred in patients with kidney disease. NSF can pose a serious and potentially fatal risk to patients with CKD, and the FDA has sought to limit the use of currently available contrast agents in this patient population. Currently there is no effective treatment for NSF.
Ferumoxytol is an iron.based agent with unique superparamagnetic properties that may be visualized by MRI. There are no iron.based PAD contrast agents currently approved for MRI in the U.S. The FDA has granted Fast Track designation to ferumoxytol for its development as a diagnostic agent for vascular.enhanced MRI to improve the assessment of suspected PAD in patients with known or suspected CKD. The Fast Track process is designed to facilitate the development and expedite the FDA's review of products and is intended to bring valuable treatments more quickly to patients in need. We have enrolled approximately two.thirds of our 108 patient Phase II study of ferumoxytol for vascular.enhanced MRI for the detection of clinically significant arterial stenosis or occlusion.
We currently have exclusive world.wide rights to market and sell ferumoxytol as an imaging agent.
【2009 Competition】The pharmaceutical and biopharmaceutical industries are subject to intense competition and rapid technological change. We have competitors both in the U.S. and internationally, and many have greater financial and other resources and more experienced trade, sales and manufacturing organizations than we do. In addition, many of our competitors have name recognition, established positions in the market and long.standing relationships with customers and distributors. Feraheme's two primary competitors are Venofer®, which is marketed in the U.S. by Fresenius Medical Care North America, or Fresenius, and American Regent Laboratories, Inc., or American Regent, a subsidiary of Luitpold Pharmaceuticals, Inc., or Luitpold, and Ferrlecit®, which is marketed by Sanofi.Aventis U.S. LLC. Products developed by our competitors may be or may be perceived to be safer, more effective, and/or easier to administer or have more favorable pricing, insurance coverage, coding and reimbursement than Feraheme. In addition, further technological and product developments may make other iron replacement therapy products more competitive than Feraheme, which would adversely impact sales of Feraheme as an iron replacement therapeutic agent if such products are approved by the FDA. We may not be able to compete successfully with these companies. We believe that our ability to successfully compete depends on a number of factors, including the timing and scope of regulatory approval of additional indications and geographies for Feraheme and of products by our competitors, our ability to obtain and maintain favorable pricing, insurance coverage, coding and reimbursement for Feraheme, our ability to implement effective marketing campaigns, the effectiveness of our sales force, our ability to maintain favorable patent protection for Feraheme, market acceptance of Feraheme and our ability to manufacture sufficient quantities of Feraheme at commercially acceptable costs.
The iron replacement therapy market is highly sensitive to several factors including, but not limited to, the perceived safety profile of the available products, the ability to obtain appropriate insurance coverage, coding and reimbursement, price competitiveness, and product characteristics such as convenience of administration and dosing regimens. To date, we have not conducted any head.to.head clinical studies comparing Feraheme to other IV iron replacement products.
There are currently two options for treating IDA in CKD patients: oral iron supplements and IV iron. The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative guidelines recommend IV iron administration for hemodialysis patients with stage 5 CKD, and either oral or IV iron for peritoneal dialysis patients and non.dialysis patients with stages 1 through 5 CKD. However, oral iron supplements are poorly absorbed by many patients, which may adversely impact their effectiveness, and are associated with certain side effects that may adversely affect patient compliance in using such products. The alternative, IV iron, is currently available in the U.S. as ferumoxytol, iron sucrose, sodium ferric gluconate, or iron dextran. The IV iron products comprised of iron sucrose or sodium ferric gluconate are typically administered as a slow push or a fifteen to sixty minute infusion in doses of 100 to 200 milligrams, thus requiring five to ten physician visits and repeated IV access for patients to receive a standard one gram therapeutic course. The iron dextran products are typically administered as a slow push in 100 milligram doses and also require five to ten physician visits to receive a standard one gram therapeutic course. Feraheme is administered as a 510 milligram injection followed by a second 510 milligram injection three to five days later, each of which can be administered in as fast as 17 seconds at a regular office visit or during dialysis treatment without the use of infusion equipment or prolonged medical intervention.
Feraheme currently competes with four IV iron products in the U.S. for the treatment of IDA in CKD patients. Its two primary competitors are Venofer®, an iron sucrose complex, and Ferrlecit®, a sodium ferric gluconate. Venofer® is currently approved for use in hemodialysis, peritoneal dialysis and non.dialysis dependent CKD patients. Ferrlecit® is approved for use only in hemodialysis patients. Dexferrum® is an iron dextran product marketed by American Regent, and INFeD®, also an iron dextran product, is marketed by Watson Pharmaceuticals, Inc., or Watson. Both iron dextran products are used in patients with documented iron deficiency in whom oral iron administration is unsatisfactory or impossible.
Based on sales data provided by IMS Health Incorporated, or IMS Health, we estimate that the size of the 2009 U.S. IV iron replacement therapy market was approximately 1.6 million grams, which represented an increase of approximately 8% over 2008. Of the estimated 1.6 million grams sold in the U.S. IV iron therapy replacement market in 2009, sales of Venofer® and Ferrlecit® represented approximately 67% and 21%, respectively. Dexferrum® and INFeD® together accounted for approximately 11% of sales of grams of iron in the U.S. market in 2009. Feraheme accounted for approximately 1% of sales of grams of iron in the U.S. market in 2009.
We compete primarily in two segments of the iron replacement therapy market: the dialysis market and the non.dialysis market.
The dialysis market is the largest and most established market for IV iron replacement therapies, with two companies serving a significant majority of all dialysis patients in the U.S. Fresenius, and DaVita, Inc., or DaVita, together treat more than two.thirds of the U.S. dialysis population. In September 2008, Fresenius finalized an exclusive sublicense agreement with Luitpold, the U.S. licensing partner of Vifor Pharma, a subsidiary of Galenica Ltd., or Galenica, to manufacture, sell and distribute Venofer® to independent outpatient dialysis clinics in the U.S. Luitpold retains the right to sell Venofer® in the U.S. to any other customer. In addition, Galenica, Vifor Pharma, and Fresenius entered into a strategic joint.venture, which became effective on January 1, 2009, to market and distribute Venofer® and Ferinject® in the dialysis market in Europe, the Middle East, Africa and Latin America. Fresenius has significant experience selling and distributing dialysis equipment and supplies to outpatient dialysis clinics and, as a result of these agreements, it may be more difficult for us to penetrate the dialysis market, in particular at their clinics.
We believe there is a significant opportunity for Feraheme in the treatment of IDA in CKD patients not yet on dialysis. The non.dialysis IV iron market is comprised primarily of three segments: hospitals, hematology clinics and nephrology clinics. The only primary competitor currently approved for use in non.dialysis dependent CKD patients is Venofer®. Our ability to effectively compete with Venofer® in the non.dialysis CKD market depends in part upon our ability to gain formulary access in hospitals and effectively promote Feraheme to physicians who treat non.dialysis CKD patients.
In December 2009, Pharmacosmos A/S, or Pharmacosmos, received a positive recommendation in 22 European countries and a final marketing authorization in Denmark, Iceland and the Netherlands to market Monofer® (iron isomaltoside 1000), its injectable iron preparation for the treatment of IDA. During 2008, Pharmacosmos completed two Phase III non.comparative open.label studies of IV iron oligosaccharide in CKD patients as well as in congestive heart failure patients. Pharmacosmos is currently recruiting patients for a Phase III comparative open.label study of IV iron oligosaccharide in patients with inflammatory bowel disease and IDA. It is too early to determine whether Monofer® will gain any meaningful share of the IV iron market in any country in which it has been approved.
In addition to the foregoing currently marketed products, there are several iron replacement therapy products in various stages of clinical and commercial development in the U.S. and abroad,
including Injectafer®, which is known as Ferinject® in Europe, and soluble ferric pyrophosphate, a form of iron given as part of the hemodialysis procedure.
Galenica, through its subsidiary Vifor (International) Inc., or Vifor, exclusively licenses Injectafer® to Luitpold and American Regent for marketing and sale in the U.S. and Canada. Injectafer® is in development for a variety of anemia.related indications, including the treatment of IDA in CKD patients, whether or not on dialysis. In March 2008, Luitpold received a non.approvable letter from the FDA for Injectafer® for the treatment of IDA in postpartum women and women with heavy uterine bleeding in the U.S. Luitpold initiated five clinical trials during 2008 and 2009 in an effort to provide additional data to address the concerns of the FDA. In June 2007, the UK Medicines and Healthcare Products Regulatory Agency approved the registration of Ferinject®, and it was simultaneously registered in a total of 18 EU countries. Ferinject® is currently marketed in at least 12 European countries. In November 2009, Vifor completed a Phase III study of patients with chronic heart failure and iron deficiency. In addition, Vifor is sponsoring ongoing Phase III trials for Ferinject® for the treatment of anemia in patients with inflammatory bowel disease and has stated that it is planning to initiate a Phase IIIb study to evaluate the long.term efficacy of Ferinject® in non.dialysis dependent CKD patients with IDA.
Rockwell Medical, or Rockwell, is developing an iron supplemented dialysate product, a form of iron given as part of the hemodialysis procedure, to be used as a treatment for IDA in dialysis patients. Rockwell has completed a Phase IIb clinical trial and has stated that it intends to initiate Phase III trials in the second half of 2010. We do not know when this product might be submitted to the FDA for approval or marketed. If shown to be safe and effective for the treatment of IDA, this product could compete with Feraheme in the dialysis market segment.
In addition to competition from other marketed products and products known by us to be currently under development, the market opportunity for Feraheme could be negatively affected if generic IV iron replacement therapy products were to be approved and achieve commercial success. For example, in July 2009, Watson announced that it entered into a license agreement with GeneraMedix, Inc., or GeneraMedix, for the exclusive U.S. marketing rights to a generic version of Ferrlecit®, which is indicated for the treatment of IDA in hemodialysis patients receiving supplemental ESA therapy. GeneraMedix has filed an Abbreviated NDA with the FDA, which is under expedited review. Companies that manufacture generic products typically invest far less resources in research and development than the manufacturer of a branded product and can therefore price their products significantly lower than those already on the market. It remains unclear if and when a generic product will enter this market. If any of these product candidates are approved for marketing and sale by the FDA, our efforts to market and sell Feraheme and our ability to generate additional revenues and achieve profitability could be adversely affected.
●GastroMARK 【2009】GastroMARK, our oral contrast agent used for delineating the bowel in MRI, is approved and marketed in the U.S., Europe, and other countries through our marketing partners. Sales of GastroMARK by our marketing partners have been at their current levels for the last several years, and we do not expect sales of GastroMARK to change materially. GastroMARK was approved by the FDA in 1996. Our marketing partner, Covidien, Ltd., or Covidien, or its predecessors, have been marketing GastroMARK in the U.S. since 1997. We initially licensed the marketing rights to GastroMARK on an exclusive basis to Guerbet S.A., or Guerbet, in western Europe and Brazil. Guerbet has been marketing GastroMARK in several EU countries since 1993 under the tradename Lumirem® and subsequently acquired the rights to market GastroMARK in several other countries in South America, the Middle East, southeast Asia, Africa, and eastern Europe. See "Licensing, Marketing and Supply Arrangements."
● 【】
●AMAG Pharmaceuticals, Inc ●Products Feraheme® (ferumoxytol) GastroMARK® (ferumoxsil) ■Investors ●SEC Filings 10-K Annual report[2010.2.26] - [pdf,151p] - [doc] - [xls] ●Financial Report ★Annual Report 2009 Annual Report ●Press Releases AMAG Pharmaceuticals and Takeda Announce Acceptance of Submission of Feraheme(R) Marketing Authorization Application to the European Medicines Agency[2010.6.29]
AMAG Pharmaceuticals to Host Conference Call to Discuss Strategic Collaboration with Takeda Pharmaceutical Company for Feraheme(R) in Select Ex-US Territories[2010.4.1]
AMAG Pharmaceuticals and Takeda Pharmaceutical Company Announce Strategic Collaboration for Feraheme(R) in All Therapeutic Indications in Select Ex-US Territories, Including Europe[2010.4.1]
AMAG Pharmaceuticals Provides Feraheme(R) Safety Update[2010.2.5]
AMAG Pharmaceuticals, Inc. Announces Data Presentations at the American Society of Nephrology (ASN) Renal Week Meeting[2009.10.7]
AMAG Pharmaceuticals Announces U.S. Launch of Feraheme(TM) (ferumoxytol) Injection[2009.7.13]
FDA Approves Feraheme(TM) to Treat Iron Deficiency Anemia in Adult Chronic Kidney Disease Patients[2009.6.30]
FDA Decision on Feraheme NDA Expected Within Next Few Days[2009.6.29]
AMAG Pharmaceuticals Announces New PDUFA Date for Feraheme(TM) (ferumoxytol injection)[2009.5.12]
■Amersham Plc
-http://www.amersham.com/index.html; 本社－英国；医用診断機器、ライフサイエンス 分野の世界企業。 従業員10,000以上、年間売上(2002) ￡1.62 billion ($2.54 billion)。 世界30か国に研究・製造施設、50か国に販売施設をもつ。 ★2003.10.10にGEによる買収が行われ、2004.4.8に完了。(詳細) GE Healthcare -http://www.gehealthcare.com/ ★Amersham plcを２つの事業で組織される。 Amersham Health (medical diagnostics and therapy products)および Amersham Biosciences (バイオ；discovery systems and protein separations). ★歴史 Amersham plcは、1997年にAmersham International (UK), Pharmacia Biotech (Swede n) and Nycomed (Norway)の３社合併により誕生。 註) Pharmacia Biotech(1967-1997): それ以前はPharmacia Amersham International() ;当初英政府出資The Radiochemical Centreとして 25年間、1982年私企業化Amersham ・The Radiochemical Centre; Amersham International; Nycomed Amersham; Amersham plc ・Nycomed; Nycomed Amersham Imaging; Amersham Health ・Pharmacia; Pharmacia Biotech; Amersham Pharmacia Biotech; Amersham Biosciences ■売上 (単位￡) 2003 2002 2001 ●Amersham Health 973(+7) 948(+8%) 922(+13) ★医療用診断薬 924(+9) 886 ※造影剤 Omnipaque 218(+2) 222(+6%) (iohexol) 非イオンX線/CT循環器・神経・腫瘍[特許off] Visipaque 122(+38) 91(+18) (iodixanol) 非イオンX線/CT循環器系 [特許2008-2011] Omniscan 106(+12) 96(+17) (gadodiamide) MRI中枢神経・循環器 [2007-2009] Optison (human albumin microspheres containing perflutren) 心筋[2012-2013] ※放射性医薬品 Myoview 149(+20) 133(+26) (99mTc-tetrafosmin kit) 心血流・乳癌[2009-2010] ★治療薬 49(-17) 62 ●Amersham Biosci 679 670(+6%) 681(+12) 蛋白分離 295(+5) 276 探索システム 384(-2) 394
全売上 1652(+6) 1618 ■地域別売上 (単位￡) 2002 2002 2001 従業員数 北米 807 799(+8) 2,900 欧州 462 428(+8) 6,200 日本 247 264(+1) 250 アジア太平洋 95 80 その他 41 47 700
全売上 1652(+6) 1618 ■Market Report: Medical Diagnostics/Radiotherapy[Amersham AnnualReport 2002] ※米国市場シェア Amersham 38%, Bracco 18%, Tyco Healthcare(Mallinckrodt Imaging) 14%, Schering 12%, Bristol-Myers Squibb(BMS) Medical Imaging(formerly Dupont) 12%, Guerbet 2%, その他 4% ※診断機器 X-ray/CT MRI 放射性診断薬 超音波診断 Total scans 630m 40m 140m Enhanced scans 75m 10m 28m 0.5m 市場規模 ￡1.4bn ￡320m ￡1.1bn ￡10m (1.5万台上) (1.5万台上) (15万台上) GammaCamera
●Amersham Plc -http://www.amersham.com/index.html ●Investors Annual reports Financial archives ●News & Events Preliminary Results for the 12 months ended 31 December 2003[2004.2.17] 1999/1-以降がWEB検索可 ●開発品目 Annual Report 2002に記載がなく Preliminary Results for the 12 Months ended 31 December 2002[2003.2.26]参照。 ●FastFact 2003 - 個別製品売り上げ、製品シートなど ■日本 Amersham KKとして日本支社あり。 日本メディフィジックス、第一製薬との契約あり。
●Amersham Health (旧 Nycomed Amersham Imaging) ●Product Information 要ID --米国以外 ●Amersham Health-US ★Product Catalog
●アマシャム バイオサエインス株式会社 設立1998年4月、従業員数 約240名、売上高 約180億円(2003年) 事業内容 バイオテクノロジー関連機器および試薬の輸出入販売 主力製品 液体クロマトグラフィー装置、ゲル坦体、DNAシークエンサー、マイクロアレイ、 ラジオアイソトープ標識化合物など (略歴) 1973年 スウェーデン国 Pharmacia AB 日本法人設立 1981年 英国 Amerham International plc 日本法人設立 1998年 4月 アマシャム株式会社 とファルマシア バイオテク株式会社が合併 アマシャム ファルマシア バイオテク株式会社設立 2002年 1月 アマシャム バイオサイエンス株式会社へ社名変更 from 会社概要 ●製品 ●テクノロジー ●プレスリリース
●日本メジフィジックス株式会社 - http://www.nmp.co.jp/ - [設立]1973年3月20日 [出資比率] 住友化学工業株式会社 50%/アマシャムグループ 50% 事業目的 放射性医薬品、診断用薬、医療用具および関連製品の研究、開発、製造、販売ならびに輸出入 [沿革] 1973年 3月 米国メジフィジックス（MPI）、住友化学工業株式会社、住友商事株式会社の合弁会社として設立 1975年 3月 MPIに代わり、日本ロシュ株式会社が株主になる 1994年 3月 日本ロシュ株式会社が株主より撤退 12月 英国アマシャム・インターナショナルが株主となる 1996年 9月 アマシャム株式会社のヘルスケア事業部門と統合 10月 住友化学工業株式会社とアマシャム・インターナショナルの折半出資体制となる 1997年10月 英国アマシャム・インターナショナルのヘルスケア部門とニコメッド（ノル ウェー）との合併に伴い、新会社ニコメッド・アマシャム（現アマシャム）が株主となる 2000年 3月 NMPビジネスサポート株式会社設立 2001年 4月 住友製薬株式会社とそれぞれの体外診断薬事業を分離・統合し設立した住友 製薬バイオメディカル株式会社営業開始 2004年 4月 ゼネラルエレクトリック（GE）グループによるアマシャム買収が成立 ●核医学診断 ●医療関係者のページ ～放射性医薬品・製品一覧、添付文書情報 ●ニュースリリース
■Amgen
設立1980。 本社は米国Delaware 2002.7.15 Immunexを吸収。同社Press Releaseは、Immunex Press Release Archivesとして別扱い 2004.3.29 Tularikを吸収($1.3 Billion)。同社Press Releaseは、Tularik Press Release Archives (Tularikは５品目のCandidate、肝臓癌薬T67,消化器癌薬T607,抗炎症剤T487,糖尿病薬T131,抗肥満薬T71を開発) 2005.12.14 Abgenix Inc.を吸収。同社Press Releaseは、Abgenix Press Release Archives 同社は既発売品はなく、大腸癌治療薬panitumumabを開発中。 Abgenix Inc 2005年決算 ●会社決算●製品売上高
($ milllion) 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 売上高 14,642 15,003 14,771 14,268 12,430 10,550 8,356 5,523 4,016 3,629 うち製品売上 14,351 14,687 14,311 13,858 12,022 9,977(+27) 7,868(+58) 4,991 3,511 3,202 他の収入 291 316 460 410 408 573 488 532 505 427 研究開発費 2,864 3,030 3,266 3,366 2,314 2,028 1,655 1,117 865 845 純利益 4,605 4,065
旧4,1963,078
旧3,1662,809
旧2,9503,633
旧3,6742,363 2,259 -1,392 1,120 1,139 従業員数 17,200 16,900 17,500 20,100 16,500 14,400 12,900 10,100 7,700 7,300 うち研究開発 7,850 7,000 8,200 6,500 5,600 4,700 3,400 3,800 3,800 うち販売 3,050 2,950 3,200 3,000 2,700 2,600 2,200 1,800 1,500 うち製造 3,600 5,600 6,600 5,100 4,400 3,600 2,500 2,100 2,000 うちその他 2,400 1,950 2,100 1,900 1,700 2,000 2,000 *Immunexを2002.7買収。Enbrelは2002末迄に８万人の患者に使用。Wyethは北米で販売パートナー *INFERGEN(Interferon alfacon-1) 1996年山之内製薬(現アステラス製薬)に日本での 共同開発・販売ライセンス
($ milllion) 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 1996 EPOGEN [米国内] 2,569(+5) 2,456(-1) 2,489(-1) 2,511 2,455(-6) 2601(+7) 2434.7 2260.6 2108.5 1962.9 1759.1 1382.0 1160.7 1071.9 epoetin alfa/貧血症 Aranesp 2,652(-15) 3,137(-13) 3,614(-12) 4,121(+26) 3,273(+32) 2473(+60) 1543.8 415.6 41.5 darbepoetin alfa/貧血症 米国内 1,251(-24) 1,651(-23) 2,154(-23) 2,790 2,104(+37) 1533(+56) 979.9 284.7 国外 1,401(-6) 1,486(+2) 1,460(+10) 1,331 1,169(+24) 940(+67) 563.9 130.9 Neulasta/NEUPOGEN 4,643(+0) 4,659(+9) 4,277(+9) 3,923(+12) 3,504 []/好中球減少症 Neulasta 3,355 3,318 2,880 2,710 2,288 1740 1255.0 463.5 (2002.2nd発売) pegfilgrastim/好中球減少症 米国内 2,527(+1) 2,505(+7) 2,231(+6) 2,217(+17) 1,900(+29) 1476 1175.7 463.5 国外 828(+2) 813(+25) 649(+32) 493(+27) 388(+47) 264(+230) 79.3 - NEUPOGEN 1,288 1,341 1,277 1,213 1,216 1175 1267 1380 1223.7 1256.6 1116.6 1055.7 1016.3 - filgrastim/好中球減少症 米国内 901(+1) 896(+4) 861(+4) 830(+3) 805(+3) 778(-12) 880.5 1041.7 国外 387(-13) 445(+7) 416(+9) 383(-7) 411(+4) 397(+3) 386.2 337.9 Enbrel 3,493(-3) 3,598(+11) 3,230(+12) 2,879(+12) 2.573(+35) 1900(+46) 1300 362.1 [全期換算802] etanercept/リウマチ性関節炎 米国内 3,283(-3) 3,389(+11) 3,052(+12) 2,736(+11) 2,470(+35) 1827(+46) 1253.7 346.2 国外[加] 210(+0) 209(+17) 178(+24) 143(+39) 103(+41) 73(+59) 46.3 15.9 Sensipar 651(+9) 597(+29) 463(+44) 321(+104) 157(+324) 37 [cinacalcet HCl]腎不全に伴う副甲状腺機能亢進症および副甲状腺癌患者のhypercalcemia 米国内 429 412 333 238 122 [] 国外 222 185 130 83 35 [] Vectibix 国内 - 170(+336) 39(-) - - [panitumumab]発売2006Q4;大腸癌 その他製品 343(+43) 240(+1) 68(+6) 64(+7) 60(+18) 51
旧8868.0 109.8 米国内 175 151 203 36 36 64 39.4 100.0 国外 168 89 35 28 24 24 28.6 9.8 Kineret - - - - - - 68.0 109.8 12.0 --- --- --- --- --- 01.11発売(anakinra)/リウマチ性関節炎 抗リウマチ剤;IL-1レセプター拮抗薬 米国内 - - - - - - 39.4 100.0 国外 - - - - - - 28.6 9.8 INFERGEN - - - [2001.6 Intermuneに米・加の独占ライセンス] - 14.5 26.2 16 - --- (Interferon alfacon-1) Total Product Sales 14,351(-2) 14,687(+3) 14,311(+3) 13,858(+15) 12,022(+20) 9977(+27) 7868.2(+58) 4991.2 3511.0 3202.2 3042.8 2514.4 2219.8 2088.2 米国内 11,135(-3) 11,460(+0) 11,443(+0) 11,397(+15) 9,892(+19) 8279(+22) 6763.9 4496.7 国外 3,216(+0) 3,227(+13) 2,868(+17) 2,461(+16) 2,130(+25) 1,698(+54) 1104.3 494.5 []
● 【2009】 ●Nplate(R) (romiplostim) ITP Romiplostim (Nplate(R)) is a peptibody agonist of the thrombopoietin (“TPO”) receptor. Nplate(R) is the first FDA-approved agent that acts directly to increase platelet production for the treatment of thrombocytopenia in splenectomized (spleen removed) and non-splenectomized adults with chronic ITP, who have had an insufficient response to corticosteroids, immunoglobulins or splenectomy.
In August 2008, Nplate(R) became the first FDA-approved peptibody protein, which works by raising and sustaining platelet counts representing a novel approach for the treatment of this chronic disease.
We are also evaluating romiplostim in pediatric ITP, myelodysplastic syndromes (“MDS”), and chemotherapy-induced thrombocytopenia (“CIT”). Phase 2 studies in each setting were initiated in 2006. The trials are currently ongoing and we continue to evaluate the safety and efficacy of romiplostim in these settings.
On August 22, 2008, the FDA approved Nplate(R), the first platelet producer for the treatment of thrombocytopenia in splenectomized (spleen removed) and non-splenectomized adults with chronic ITP. Nplate(R), the first FDA approved peptibody protein, works by raising and sustaining platelet counts. On February 6, 2009, we announced that the European Commission granted marketing authorization for Nplate(R) for the treatment of splenectomized adult chronic ITP patients who are refractory to other treatments (e.g. corticosteroids, immunoglobulins). In the EU, Nplate(R) may also be considered as second line treatment for adult non-splenectomized ITP patients where surgery is contra-indicated.
【2008】On August 22, 2008, the FDA approved Nplate(R), the first platelet producer for the treatment of thrombocytopenia in splenectomized (spleen removed) and non-splenectomized adults with chronic immune thrombocytopenic purpura (“ITP”). Nplate(R), the first FDA approved peptibody protein, works by raising and sustaining platelet counts. As part of the approval for Nplate(R), a REMS was developed with the FDA to assure the safe use of Nplate(R) while minimizing risk. The Nplate(R) REMS involves, among other things, healthcare provider and patient enrollment registries, tracking of patient medical history and data and follow-up safety questionnaires to healthcare providers, all of which require extensive discussion with and education of healthcare providers. In addition, on February 6, 2009, we announced that the European Commission granted marketing authorization for Nplate(R) for the treatment of splenectomized adult chronic ITP patients who are refractory to other treatments (e.g. corticosteroids, immunoglobulins). In the European Union (“EU”), Nplate(R) may also be considered as second line treatment for adult non-splenectomized ITP patients where surgery is contra-indicated. ●Vectibix(R) (panitumumab) 大腸癌 Vectibix(R) is our trademark for our first entirely human monoclonal antibody for the treatment of patients with EGFr expressing mCRC after disease progression on, or following fluoropyrimidine-, oxaliplatin- and irinotecan- containing chemotherapy regimens. EGFr is a protein that plays an important role in cancer cell signaling and is over-expressed in many human cancers. Vectibix(R) is an entirely human monoclonal antibody that binds with high affinity to EGFrs and interferes with signals that might otherwise stimulate growth and survival of the cancer cell. The goal of developing entirely human monoclonal antibodies is to offer effective targeted therapies with lessened risk of immune response against these agents. Vectibix(R) received FDA approval in September 2006. On December 5, 2007, the European Commission granted a conditional marketing authorization for Vectibix(R), which was renewed in December 2008, as a monotherapy for the treatment of patients with EGFr expressing mCRC with non-mutated (wild-type) KRAS genes after failure of standard chemotherapy regimens. We acquired full ownership of Vectibix(R) as part of our acquisition of Abgenix, Inc. (“Abgenix”) in April 2006. 【2009】 【2008】At the ODAC meeting on December 16, 2008, we discussed the clinical utility of the KRAS gene as a predictive biomarker in patients with metastatic colorectal cancer (“mCRC”) treated with anti-Epidermal Growth Factor Receptors (“EGFr”) antibody, Vectibix(R). We believe that data shared with the ODAC supports the suggestion that KRAS is a predictive biomarker for the anti-EGFr class of drugs in the monotherapy setting. In March 2008, the Journal of Clinical Oncology published results from an analysis of the first randomized, controlled clinical trial (“Study 408”), which showed that mCRC patients with mutated KRAS tumors do not respond to Vectibix(R) monotherapy. Conversely, patients with wild-type KRAS tumors treated with Vectibix(R) have a better response rate and prolonged progression-free survival (“PFS”). ●Denosumab 骨粗鬆症 【2009】kﾎ We received Complete Response Letters from the FDA on our biologics license application ("BLA") for Prolia in the treatment and prevention of postmenopausal osteoporosis ("PMO") in women and bone loss in patients undergoing hormone ablation therapy ("HALT") for either prostate or breast cancer. These Complete Response Letters requested additional information to support approval of the treatment of the PMO indication and the HALT indication, and requested a new clinical program to support approval of the prevention of the PMO indication. (The FDA has provisionally approved the trade name Prolia in the indications noted above, for which the drug is administered twice yearly subcutaneously at a 60 milligram ("mg") dose. The trade name is only for these indications and may not apply for other indications of denosumab.) kﾎ On February 19, 2010, we announced that the FDA has evaluated the content of our Complete Response submission for Prolia in the treatment of PMO, which we submitted on January 25, 2010, and classified it as a Class 2 resubmission. With the Class 2 designation, the FDA set a corresponding Prescription Drug User Fee Act ("PDUFA") action date of July 25, 2010.
kﾎ We received a positive opinion from the Committee for Medicinal Products for Human Use ("CHMP") of the European Medicines Agency ("EMA") (formerly known as the EMEA) for marketing authorization for the treatment of osteoporosis in postmenopausal women at increased risk of fractures and bone loss associated with hormone ablation in men with prostate cancer at increased risk of fractures.
kﾎ We announced positive results from the following three phase 3 head-to-head trials evaluating denosumab versus Zometa@� (zoledronic acid) in the treatment of bone metastases:
※in patients with advanced breast cancer, in which denosumab was superior to Zometa@� in delaying the time to the first skeletal-related event ("SRE") and delaying the time to the first-and-subsequent SREs,
※in advanced cancer patients with solid tumors or multiple myeloma, in which denosumab was non-inferior to Zometa@� in delaying the time to the first SRE,
※in men with advanced prostate cancer, in which denosumab was superior to Zometa@� in delaying the time to the first SRE and delaying the time to the first-and-subsequent SREs.These three studies will form the basis of the clinical evidence package for denosumab in advanced cancer, which will be submitted to regulatory authorities later in 2010.
Denosumab is a fully human monoclonal antibody that specifically targets a ligand known as RANKL (that binds to a receptor known as RANK) which is an essential regulator of osteoclasts. Denosumab is under regulatory review and is being studied across a range of conditions, including osteoporosis, treatment-induced bone loss, bone metastases, multiple myeloma and RA.
The following is a summary of certain key developments that occurred in 2009 and early 2010 with respect to denosumab:
Prolia (denosumab) for the Prevention and Treatment of PMO and the Prevention and Treatment of Bone Loss in Patients Undergoing HALT for either Prostate Cancer or Breast CancerIn late 2008, we submitted the BLA to the FDA for Prolia in the treatment and prevention of PMO in women and bone loss in patients undergoing HALT for either prostate or breast cancer.
On August 13, 2009, we announced the results of our meeting with the FDA's Advisory Committee for Reproductive Health Drugs ("ACRHD") to review the potential use of Prolia for the treatment and prevention of PMO in women and the treatment and prevention of bone loss in patients undergoing HALT for either prostate cancer or breast cancer. The Committee recommended approval of Prolia for the treatment of PMO and for the treatment of bone loss in patients undergoing HALT for prostate cancer. The Committee recommended against approval of Prolia to treat or prevent bone loss in women with breast cancer undergoing HALT until additional data are available. The Committee also recommended against approval of Prolia to prevent bone loss in low-risk patients in all three populations. Finally, the Committee recommended that Prolia have a REMS. The ACRHD is an advisory committee of external experts who advise the FDA about the safety and effectiveness of marketed and investigational human drugs for use in the practice of obstetrics, gynecology and related specialties. This committee is advisory only and FDA officials are not bound to or limited by their recommendations.
In October 2009, the FDA issued Complete Response Letters for our BLA for Prolia for the above-noted indications. The FDA issues Complete Response Letters to request additional information needed to complete the review of applications for product approval.
The Complete Response Letter related to the Prolia application for the treatment and prevention of PMO in women requested several items, including further information on the design and background adverse event rates that will inform the methodology of our previously submitted post-marketing surveillance program, although the letter did not require additional pre-marketing clinical trials to complete the review of the treatment indication. The FDA has also requested a new clinical program to support approval of Prolia for the prevention of PMO indication. In addition, the FDA has determined that a REMS is necessary for Prolia and must include a medication guide and a healthcare provider communication plan. The FDA acknowledged receipt of our previously submitted proposed REMS materials. The FDA also requested all updated safety data related to Prolia. On February 19, 2010, we announced that the FDA has evaluated the content of our Complete Response submission for Prolia in the treatment of PMO, which we submitted on January 25, 2010, and classified it as a Class 2 resubmission. With the Class 2 designation, the FDA set a corresponding PDUFA action date of July 25, 2010.
The Complete Response Letter related to the Prolia HALT application requested additional information regarding the safety of Prolia in patients with breast cancer receiving aromatase inhibitor therapy and patients with prostate cancer receiving androgen deprivation therapy ("ADT"). Specifically, the FDA has requested results from additional adequate and well-controlled clinical trials demonstrating that Prolia has no detrimental effects on either time-to-disease progression or OS. We continue to work with the FDA to determine the appropriate next steps regarding our application for the HALT indication.
Prolia Received Positive Opinion from CHMP in the EU
In December 2009, the CHMP announced a positive opinion for the marketing authorization of Prolia for the treatment of osteoporosis in postmenopausal women at increased risk of fractures, and for the treatment of bone loss associated with hormone ablation in men with prostate cancer at increased risk of fractures. If approved by the European Commission, we would receive marketing authorization for Prolia in all EU Member States. The timing of actual launch dates would vary by country based on reimbursement authority approval of pricing which could follow the EMA approval by many months. While the European Commission generally follows the CHMP's opinion, it is not bound to do so.
Prolia is also under regulatory review in Switzerland, Australia and Canada for the treatment and prevention of PMO and the treatment of bone loss in patients undergoing HALT for breast and prostate cancer. We are working closely with regulatory agencies in each of these countries.
Denosumab Phase 3 Bone Metastases Clinical Trials
In 2009, we announced that the phase 3 head-to-head trial evaluating denosumab versus Zometa@� in the treatment of bone metastases in patients with advanced breast cancer met its primary endpoint of non-inferiority in time to first SRE and its secondary endpoints (superiority compared to Zometa@� for both delaying the time to the first on-study SRE and delaying the time to the first-and-subsequent SREs). We also announced that the phase 3 head-to-head trial evaluating denosumab versus Zometa@� in the treatment of bone metastases in advanced cancer patients with solid tumors (not including breast and prostate cancer) or multiple myeloma met its primary endpoint of non-inferiority in time to first SRE. On February 8, 2010, we announced that the phase 3 head-tohead trial evaluating denosumab versus Zometa@� in the treatment of bone metastases in advanced cancer patients with prostate cancer met its primary endpoint of non-inferiority in time to first SRE and its secondary endpoints (superiority compared to Zometa@� for both delaying the time to the first on-study SRE and delaying the time to the first-and-subsequent SREs). These three studies will form the basis of the clinical evidence package for denosumab in advanced cancer, which will be submitted to regulatory authorities later in 2010. For more information, see "Research and Development and Selected Product Candidates."
Patents and Competition
Our outstanding material patents for denosumab are described in the table below.
Territory General Subject Matter Expiration(1) U.S. RANKL antibodies 12/22/2017 U.S. Methods of treatment 11/11/2018 U.S. RANKL antibodies 11/28/2023 Europe RANKL antibodies 12/22/2017 Europe Methods of treatment 4/15/2018 Europe RANKL antibodies 2/23/2021
(1) The expiration dates may be subject to change if delays in regulatory approval lead to extensions of patent terms in the United States and/or supplemental protection in Europe.The following table and discussion reflect other companies and their currently marketed products that will compete with denosumab, if approved. This table and discussion of competitor marketed products and potential competitor products may not be exhaustive. Merck's patent covering the use of FOSAMAX@� to treat bone loss expired in the United States in February 2008. Following the patent expiry, generic alendronate ("ALN") became available from Teva and other companies, which competes with FOSAMAX@� .
Therapeutic Area Competitor Marketed Product Potential Competitor PMO FOSAMAX@� Merck PMO Actonel@� Warner Chilcott/Aventis PMO Boniva@� /Bonviva@� Roche/GSK PMO Evista@� Eli Lilly PMO Forteo@� /Forsteo Eli Lilly PMO Miacalcin@� Novartis AG ("Novartis") PMO Aclasta@� /Reclast@� Novartis PMO Conbriza@� Pfizer PMO Fablyn@� Pfizer Oncology Zometa@� Novartis Oncology Aredia@� Novartis 【2008】Denosumab is the first fully human monoclonal antibody in late stage clinical development that specifically targets a ligand known as RANKL (that binds to a receptor known as RANK), an essential regulator of osteoclasts (the cells that break down bone). Denosumab is being investigated for its potential to inhibit all stages of osteoclast activity through a targeted mechanism. In December 2008, we submitted a biologics license application (“BLA”) to the FDA for denosumab for the treatment and prevention of postmenopausal osteoporosis (“PMO”) in women and bone loss in patients undergoing hormone ablation for either prostate or breast cancer. On February 18, 2009, the FDA accepted our BLA and informed us that it will target an FDA action within ten months of the BLA’s submission date, resulting in a Prescription Drug User Fee Act (“PDUFA”) action date of October 19, 2009. The FDA indicated that it intends to simultaneously review the data we submitted for both the PMO and bone loss in patients undergoing hormone ablation for prostate or breast cancer indications due to the interdependency of the data across the indications from more than 11,000 patients included in support of the BLA. Additionally, in January 2009, we submitted an application to the EMEA for the approval of denosumab for treatment of PMO in women and treatment of bone loss associated with hormone ablation therapy in patients with breast and prostate cancer. In addition, during 2008, we announced results of the following key trials involving denosumab. Osteoporosis
On September 16, 2008 at the American Society of Bone and Mineral Research (“ASBMR”) annual meeting, we presented detailed results from the pivotal fracture trial (“Study 216”) evaluating denosumab in the treatment of PMO. In this pivotal, three-year, international, phase 3 study of approximately 7,800 women with osteoporosis, patients were randomized to receive either denosumab, given by subcutaneous injection once every six months, or placebo injections. For the primary endpoint, treatment with denosumab resulted in a statistically significant reduction (68%) in the incidence of new vertebral fractures compared with placebo treatment (2.3% for denosumab versus 7.2% for placebo, p=0.0001). In addition, women receiving denosumab experienced a statistically significant reduction (20%) in the incidence of new non-vertebral fractures compared with placebo treatment (6.5% for denosumab versus 8.0% for placebo, p=0.011) and a statistically significant reduction (40%) in the incidence of hip fractures compared with placebo treatment (0.7% for denosumab versus 1.2% for placebo, p=0.036), each a secondary endpoint. The incidence and types of both adverse and serious adverse events observed in this study, including serious infections and neoplasms, were similar between the denosumab and placebo groups. The most common adverse events across both treatment arms were arthralgia, back pain, hypertension and nasopharyngitis.
In addition to the detailed results of Study 216, we presented the results of two non-pivotal phase 3 studies of denosumab in osteoporosis at the ASBMR meeting. The first was a phase 3 head-to-head, double-blind trial known as the Study of Transitioning from AleNdronate to Denosumab trial (“STAND”) (“Study 234”). The results of this study demonstrated that subcutaneous injections of denosumab every six months achieved significantly greater increases in bone mineral density (“BMD”) versus those achieved with alendronate (“ALN”) at all sites measured. For the primary endpoint, denosumab resulted in significant increases in BMD at the total hip compared with ALN (1.9% for denosumab versus 1.05% for ALN, p<0.0001). Treatment with denosumab also resulted in significant increases in BMD compared with continued ALN treatment at all secondary endpoints, including the lumbar spine, femoral neck, hip trochanter and 1/3 radius. The incidence and types of adverse events observed in the study, including neoplasms and infection, were similar between the denosumab and ALN treatment groups. The most common adverse events across both treatment arms were back pain, arthralgia and nasal pharyngitis. The second non-pivotal study was a head-to-head trial comparing denosumab to weekly oral ALN, also known as the Determining Efficacy: Comparison of Initiating Denosumab versus Alendronate trial (“DECIDE”) (“Study 141”). As a part of this study, patients were given a questionnaire after 12 months of treatment to gauge preference on mode of administration as well as satisfaction with frequency of dosing of twice-yearly subcutaneous injections versus weekly oral tablet. More than three-quarters of patients in both study arms preferred subcutaneous injection over oral pills (77% versus 23%, p <0.0001). In addition, significantly more patients were more satisfied with twice-yearly dosing compared to weekly dosing (80% placebo injection versus 20% weekly oral ALN, and 79% for denosumab versus 21% weekly placebo tablet, p <0.0001 for both study groups).
Oncology
On July 14, 2008, we announced findings from a three-year pivotal phase 3 placebo-controlled trial evaluating denosumab in the treatment of bone loss in men undergoing androgen deprivation therapy (“ADT”) for non-metastatic prostate cancer (“Study 138”). In this study of more than 1,400 men, denosumab treatment produced statistically significantly greater increases in BMD at the lumbar spine (primary endpoint) and non-vertebral sites compared with placebo at multiple time points. These improvements in BMD were consistent with those seen in other denosumab studies evaluating BMD in women with breast cancer receiving aromatase inhibitor (“AI”) therapy, and in postmenopausal women with low bone mass. During the 36-month evaluation period, men receiving denosumab experienced less than half the incidence of new vertebral fractures (a secondary endpoint) compared with those receiving placebo, a statistically significant finding. Furthermore, in the denosumab arm there were fewer non-vertebral fractures over the 36-month period. The incidence and types of adverse events observed in this study were generally similar between the denosumab and placebo groups. The most common adverse events across both treatment arms were arthralgia, back pain, constipation and pain in extremity. Serious adverse infectious events occurred in approximately 5% of men receiving placebo treatment as compared with approximately 6% of those receiving denosumab.
●EPOGEN(R) (Epoetin alfa) reduced red blood cell count can result in anemia (see “－ Aranesp(R) (darbepoetin alfa)”). People with CRF suffer from anemia because they do not produce sufficient amounts of erythropoietin, which is normally produced in healthy kidneys. We were granted an exclusive license to manufacture and market recombinant human erythropoietin in the United States under a licensing agreement with KA. We have retained exclusive rights to market EPOGEN(R) in the United States for dialysis patients. We granted Ortho Pharmaceutical Corporation (which has assigned its rights under the Product License Agreement to Ortho Biotech) a license to commercialize recombinant human erythropoietin as a human therapeutic in the United States in all markets other than dialysis (see “Joint Ventures and Business Relationships － Johnson & Johnson”).
We launched EPOGEN(R) in the United States in 1989 for the treatment of anemia associated with CRF for patients who are on dialysis. We market EPOGEN(R) for the treatment of anemic adult and pediatric patients with CRF who are on dialysis. EPOGEN(R) is indicated for elevating or maintaining the red blood cell level (as determined by hematocrit or Hb measurements) and decreasing the need for blood transfusions in these patients.
EPOGEN(R) sales in the United States were $2.5 billion for each of the three years ended December 31, 2008.
Our outstanding material patents for Epoetin alfa are described in the table below. Territory General Subject Matter Expiration U.S. Process of making erythropoietin 8/15/2012 U.S. Product claims to erythropoietin 8/20/2013 U.S. Pharmaceutical compositions of erythropoietin 8/20/2013 U.S. Cells that make certain levels of erythropoietin 5/26/2015Any products or technologies that are directly or indirectly successful in addressing anemia associated with CRF could negatively impact product sales of EPOGEN(R). In the United States, EPOGEN(R) and Aranesp(R) compete with each other, primarily in the U.S. hospital dialysis clinic setting, and there was a conversion from EPOGEN(R) to Aranesp(R) in this setting, however we believe that the conversion has stabilized. In addition, Affymax and Takeda are co-developing Hematide?, an ESA for the treatment of anemia in renal patients. FibroGen is developing FG-2216 and FG-4592, orally active ESAs for the treatment of anemia. Additionally, in December 2008, Merck announced the formation of a new biotech division, Merck Bioventures, which is developing a late stage pegylated ESA (MK-2578), which they have announced they expect to launch in 2012.【2009 ESAs】 kﾎ On February 16, 2010, we announced that the FDA approved a REMS program for our ESAs. On February 16, 2010, Amgen and Centocor Ortho Biotech Products, L.P. ("Centocor Ortho Biotech Products"), a subsidiary of Johnson & Johnson ("J&J"), announced that the FDA approved a REMS for ESAs which includes Aranesp@� , EPOGEN@� and Procrit@� (Epoetin alfa). The FDA has determined that a REMS is necessary for ESAs to ensure the benefits of these drugs outweigh the risks of shortened overall survival ("OS") and/or increased tumor progression or recurrence as identified in clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid and cervical cancers. As part of the REMS, a medication guide explaining the risks and benefits of ESAs must be provided to all patients receiving ESAs. To ensure continued access to ESAs for healthcare providers who prescribe, or prescribe and dispense, ESAs to patients with cancer, providers are required to train and enroll in the ESA APPRISE (Assisting Providers and cancer Patients with Risk Information for the Safe use of ESAs) Oncology Program and to document that a discussion about the risks of ESAs took place with each patient prior to the initiation of each new course of ESA therapy. The ESA APPRISE Oncology Program will be launched on March 24, 2010. Direct patient registration or approval prior to ESA administration is not required through the ESA APPRISE Oncology Program.
kﾎ We published detailed results from the Trial to Reduce Cardiovascular Endpoints with Aranesp@� Therapy ("TREAT") and updated the ESA labels to incorporate certain of the trial results regarding the increased risk of stroke and to reinforce the need to follow the approved label guidance to maintain appropriate hemoglobin ("Hb") levels. On December 16, 2009, after consultation with the FDA, Amgen and Centocor Ortho Biotech Products updated the safety information in the ESA product labeling to reflect certain results of our TREAT study. These changes include a revision to the BOXED WARNINGS section to include the increased risk of stroke and to reinforce the need to follow the approved label guidance to maintain Hb levels within the range of 10 to 12 grams per deciliter ("g/dL"). (See discussion of Aranesp@� TREAT study results in "Research and Development and Selected Product Candidates.")
kﾎ The FDA announced that it will call an advisory committee meeting in 2010 to re-evaluate the use of ESAs to treat anemia in patients with chronic kidney disease ("CKD") and could consider lowering targeted Hb levels and reducing approved dosing for ESAs.
kﾎ The Centers for Medicare & Medicaid Services ("CMS") has scheduled a Medicare Evidence Development & Coverage Advisory Committee ("MEDCAC") meeting on March 24, 2010 to examine currently available evidence on the use of ESAs to manage anemia in patients who have CKD, which may consider the results of the TREAT study.
kﾎ The CMS released its proposed rule to implement the bundled prospective payment system for end stage renal disease ("ESRD"), which could impact reimbursement for EPOGEN@�
【2008】 貧血用薬の競合
Certain of our marketed products are under increased competitive pressures, including from biosimilar and other products in Europe, which compete or are expected to compete with Aranesp(R), Neulasta(R) and NEUPOGEN(R), as well as our marketed products in the United States, including ENBREL. For example, as a result of final regulatory guidelines issued by the EMEA in 2006 related to the development and approval of biosimilar products, we have experienced and expect to continue to experience increased competition throughout Europe, including from a number of biosimilar erythropoietin products, which compete with Aranesp(R). In addition, a number of granulocyte colony-stimulating factor (“G-CSF”) biosimilar products have received marketing authorization from the European Commission in 2008 and early 2009 and have been or are expected to be launched and compete with Neulasta(R) and NEUPOGEN(R). Further in the United States, ENBREL will continue to face increased competition primarily due to the expected launch of new products.
特許係争
On October 17, 2008, the Massachusetts District Court entered judgment that the patents in suit are valid and enforceable, and that the patents, identified below as the subject of the permanent injunction, would be infringed by the import, use and sale of F. Hoffmann-La Roche Ltd. (“Roche”) pegylated erythropoietin product in the United States. The Massachusetts District Court permanently enjoined Roche from infringing the ‘422 Patent, the ‘933 Patent, the ‘868 Patent and the ‘698 Patent for the remaining life of these patents. See Note 10, “Contingencies － Roche Matters － Amgen Inc. v. F. Hoffman-La Roche Ltd. et al.” for further discussion of this legal proceeding.
On July 11, 2008, we announced that we had reached an agreement to settle our antitrust litigation with Ortho Biotech Products L.P., a subsidiary of Johnson & Johnson (hereafter referred to as “Ortho Biotech” or “J&J”), which had alleged that discounts offered to oncology clinics on our NEUPOGEN(R) and Neulasta(R) and Aranesp(R) products violated antitrust laws. Under terms of the agreement, we paid Ortho Biotech $200 million and the pending litigation in New Jersey District Court was dismissed with prejudice.
【2008 癌リスク】赤血球生成促進製剤（ESA製剤）についての2つの新たな試験のデータによると、化学療法による貧血に対してESA製剤を投与された進行した乳癌、子宮頸癌の患者は、投与しない患者に比べて死亡までの期間が短縮し、腫瘍の増殖が早まった。（略）これら2つの試験は、前回2007年11月FDAがラベル改正をした後の新データである。全8つの試験で、患者はヘモグロビン値12g/dL以上を目標にESA製剤を投与されていたが、ほとんどの患者はその目標値に及んでいなかった。 医薬品安全性情報 Vol.6 No.26 （ 2008/12/25 ） 医薬品安全性情報 Vol.6 No.20 （ 2008/10/02 ） ESA Regulatory and Reimbursement Developments
The ESA regulatory and reimbursement developments in 2008 reflect a continuation of events that began in late 2006 that affected the class of ESA products, including Aranesp(R) and EPOGEN(R). Certain of the developments discussed below have had a material adverse impact on sales of our ESA products, in particular Aranesp(R) sales in the U.S. supportive cancer care setting.
Beginning in late 2006, adverse safety results involving ESA products were observed in various studies that were performed by us and by others (including our licensees or independent investigators) that explored the use of ESAs in settings different from those outlined in the FDA approved label, including targeting higher hemoglobin (“Hb”) levels and/or use in non-approved patient populations. The results of these studies culminated in significant regulatory and reimbursement developments affecting the class of ESA products, including Aranesp(R) and EPOGEN(R). For example, in February 2007, following the reported results from our Anemia of Cancer phase 3 study (the “AoC 103 study”), the United States Pharmacopoeia Dispensing Information (“USP DI”) Drug Reference Guides removed Aranesp(R) in the treatment of anemia of cancer (“AoC”). Thereafter, Aranesp(R) use in AoC essentially ceased. In addition, during 2007, we had discussions with the FDA and other regulatory authorities and meetings with certain of the FDA’s advisory panels, which led to further developments. For example, in March 2007, the product labeling information for the class of ESAs was updated, including a boxed warning in the prescribing information (“PI”). In addition, in November 2007, following our meeting with the Oncologic Drugs Advisory Committee (“ODAC”) in May 2007, various additional safety-related revisions were again made to the ESA label. Further, in July 2007, the Centers for Medicare and Medicaid Services (“CMS”) issued its National Coverage Decision Memorandum for Use of Erythropoiesis Stimulating Agents in Cancer and Related Neoplastic Conditions (the “Decision Memorandum”). The Decision Memorandum established the ESA reimbursement policy for Medicare and other government beneficiaries who are treated for chemotherapy-induced anemia (“CIA”) with ESAs. We believe that the restrictions in the Decision Memorandum changed the way ESAs are used in clinical practice by decreasing the number of treated patients, the average dose and duration of ESA therapy.
Discussions with regulatory authorities, including the FDA, regarding safety concerns with respect to the administration of ESA products in various settings continued throughout 2008, resulting in further regulatory developments. The following is a summary of selected key regulatory and related developments that occurred in 2008.
During 2008, the ESA labeling information was further revised to reflect various safety concerns, beginning in March 2008, with an updated boxed warning in the labeling information in the United States. This updated box warning states that ESAs shorten overall survival and/or time-to-tumor progression in clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid and cervical cancers when dosed to a target Hb level of greater than or equal to 12 grams per deciliter (“g/dL”). Additionally, on August 6, 2008, we revised the ESA product labeling, as the FDA directed, based on a complete response letter, received on July 30, 2008, from the FDA to the revisions to the ESA labeling we proposed following the March 13, 2008 ODAC meeting. The revised labeling included, among other things, (i) the addition to the boxed warning of a statement that ESAs are not indicated for patients receiving myelosuppressive therapy when the anticipated outcome of such therapy is cure, (ii) the addition of a statement in the DOSAGE and ADMINISTRATION section of the label that ESA therapy should not be initiated at Hb levels 3 10 g/dL and that dose should be adjusted to maintain the lowest Hb level sufficient to avoid red blood cell transfusions and (iii) the removal of reference to the upper safety limit of 12 g/dL. Further, following the closed meeting by the Scientific Advisory Group on Oncology (“SAG-O”) in May 2008, we received notification in October 2008 that the European Commission had approved updates to the Aranesp(R) product information. The product information for all ESAs was updated to advise that in some clinical situations blood transfusions should be the preferred treatment for the management of anemia in patients with cancer and that the decision to administer ESAs should be based on a benefit-risk assessment with the participation of the individual patient. This assessment should take into account the specific clinical context, including the type of tumor and its stage, the degree of anemia, life-expectancy, the environment in which the patient is being treated and patient preference.
In addition, on January 1, 2008, the CMS’ revisions to its Erythropoietin Monitoring Policy (“EMP”) became effective, which require a 50% reduction in Medicare reimbursement if a patient’s Hb level is above 13 g/dL for three or more consecutive months. In addition, the EMP reduces the monthly dosing limits to 400,000 international units (“IUs”) of EPOGEN(R), from 500,000 IUs, and to 1,200 micrograms (“mcgs”) of Aranesp(R), from 1,500 mcgs. We believe that the EMP implementation in January 2008 has significantly affected physician behavior resulting in declines in dosing trends as particularly noted in the quarter of implementation. However, this dose decline subsequently stabilized in 2008 but may further fluctuate in the future.
Further, on September 30, 2008, we announced that we had received a summary of preliminary results from the Cochrane Collaboration’s independent meta-analysis of patient-level data from previously conducted, randomized, controlled, clinical studies evaluating ESAs in cancer patients which we submitted to the FDA and the European Agency for the Evaluation of Medical Products (“EMEA”). These results were also presented by the Cochrane Haematological Malignancies Group in December at the 2008 American Society of Hematology (“ASH”) Congress.
This Cochrane meta-analysis of patient level data from previous studies corroborates prior analyses indicating that the use of ESAs may increase the risk of death in cancer patients. The studies in the analysis all predate the current label, which advises using the least amount of ESA necessary to avoid transfusion.
The analyses on all cancer patients were based on 53 previously conducted studies involving 13,933 patients. None of these studies utilized ESAs according to current label guidance. The overall survival results corroborate an earlier review by the Cochrane Collaboration, published in 2006, which is included in the WARNINGS section of the current U.S. PI (Hazard Ratio (“HR”): 1.08 [95% Confidence Interval (“CI”) 0.99 - 1.18]). The ESA treatment arm had increased on-study deaths (HR: 1.17 [95% CI 1.06 - 1.30]) and decreased overall survival (HR: 1.06 [95% CI 1.00 - 1.12]) compared to controls. The analyses on patients undergoing chemotherapy, the cancer indication for which ESAs are approved, were based on 38 studies with 10,441 patients. None of these studies utilized ESAs according to current label guidance. The ESA treatment arm had increased on-study deaths (HR: 1.10 [95% CI 0.98 - 1.24]) and decreased overall survival (HR: 1.04 [95% CI 0.97 - 1.11]) compared to controls. While neither of these results is statistically significant, they do not exclude the potential for adverse outcomes when ESAs are prescribed according to the current label. The final report on these endpoints is expected in 2009.
Our ESA products will continue to face future challenges. For example, we continue to work with the FDA to finalize a new protocol for a clinical trial to determine the effects of ESAs on survival and tumor outcomes in anemic patients with metastatic cancer receiving concomitant myelosuppressive chemotherapy. We have submitted an Aranesp(R) study protocol to the FDA and plan to initiate the study in 2009. In addition, in response to the FDA’s request under authority prescribed by the Food and Drug Administration Amendments Act of 2007 (the “FDAAA”), we continue to work closely with the FDA to develop a REMS program for the class of ESA products. We have submitted a proposed REMS in response to the FDA’s requests. The components of the REMS approved by the FDA could be different for the use of ESAs in the oncology and nephrology indications. We believe that a REMS program for our ESA products could have a material adverse impact on the future sales of Aranesp(R), especially in the U.S. supportive cancer care setting. Additionally, future Aranesp(R) sales could also be materially adversely impacted by further changes in reimbursement, including as a result of future regulatory developments.
【2006】 EPOGEN(R) is Amgen's registered trademark for its recombinant human erythropoietin product, a protein that stimulates red blood cell production. A reduced red blood cell count can result in anemia (see “－ Aranesp(R) (darbepoetin alfa)”). People with chronic renal failure suffer from anemia because they do not produce sufficient amounts of erythropoietin, which is normally produced in healthy kidneys.
We were granted an exclusive license to manufacture and market recombinant human erythropoietin in the United States under a licensing agreement with KA. We have retained exclusive rights to market EPOGEN(R) in the United States for dialysis patients. We granted Ortho Pharmaceutical Corporation (which has assigned its rights under the Product License Agreement to Ortho Biotech Products, L.P., a subsidiary of Johnson & Johnson, hereafter referred to as “Ortho Biotech Products, L.P.” or “Johnson & Johnson”) a license to commercialize recombinant human erythropoietin as a human therapeutic in the United States in all markets other than dialysis Table of Contents(see “Joint Ventures and Business Relationships － Johnson & Johnson”). Johnson & Johnson markets recombinant human erythropoietin under the trademark PROCRIT(R) in the United States (see Note 1, “Summary of significant accounting policies ? Product sales” to the Consolidated Financial Statements).
We launched EPOGEN(R) in the United States in 1989 for the treatment of anemia associated with chronic renal failure for patients who are on dialysis. EPOGEN(R) is approved for the treatment of anemic adult and pediatric patients with chronic renal failure who are on dialysis. EPOGEN(R) is indicated to elevate or maintain the red blood cell level (as determined by hematocrit or hemoglobin measurements) and to decrease the need for blood transfusions in these patients.
EPOGEN(R) sales for the years ended December 31, 2006, 2005 and 2004 were $2,511 million, $2,455 million and $2,601 million, respectively.
【2006】貧血用薬の競合
We are committed to growing our anemia business and maintaining our leadership in anemia management, which includes impacting patient health outcomes and supporting the development of new standards of care, exploring new technologies in anemia therapy, preparing to compete with F. Hoffmann-La Roche Ltd. (“Roche”) in the U.S. and with biosimilar and other competing products in Europe and defending our intellectual property. Roche is developing a pegylated recombinant human erythropoietin (“peg-EPO”) for which they have filed a biologic license application (“BLA”) with the FDA and, according to Roche's public statements, they expect to launch the molecule in the U.S. nephrology segment in 2007 despite our ongoing lawsuit and their acknowledgement of our U.S. erythropoietin patents
Certain of our products are expected to face competition in certain geographic areas from biosimilar products. Our principal European patent relating to erythropoietin expired on December 12, 2004 and our principal European patent relating to G-CSF expired on August 22, 2006. We believe that as these patents have expired, other companies could receive approval for and market biosimilar products to compete with our products in the European Union (“EU”). (See “Item 1A. Risk Factors - Our marketed products face substantial competition and other companies may discover, develop, acquire or commercialize products before or more successfully than we do.”)
While we do not market EPOGEN(R) in Europe as this right belongs to Johnson & Johnson (through KA), we do market Aranesp(R) in the EU, which competes with Johnson & Johnson's EPREX(R) product, Roche's NeoRecormon(R) product and others' erythropoietin products. We expect that biosimilar erythropoietin products may be approved in the EU in 2007 and could be available in the EU shortly after approval. Based on an announcement by Shire Pharmaceuticals Group plc ("Shire"), we expect that a competing erythropoietin product, manufactured by Shire, may appear on the market in the EU in 2007. In addition, Roche is developing its peg-EPO product which, upon regulatory approval, we expect they will launch in the EU nephrology segment in 2007. In 2006, the European Medicines Agency (“EMEA”) developed and issued final regulatory guidelines related to the development and approval of biosimilar products. The final guidelines included clinical trial guidance for certain biosimilar products including erythropoietins and G-CSFs, which guidance recommends that applicants seeking approval of such biosimilar products conduct fairly extensive pharmacodynamic, toxicological, clinical safety studies and a pharmacovigilance program. In the United States, there currently is no legal approval pathway for follow-on biologic products. A number of events would need to occur before these products could enter the market, including passage of legislation by Congress to create a new approval pathway and promulgation of associated regulations and guidance by the FDA.
●Aranesp(R) (darbepoetin alfa) Aranesp(R) is our registered trademark for one of our ESAs, a protein that stimulates red blood cell production. Red blood cells transport oxygen to all cells of the body. Without adequate amounts of erythropoietin, the red blood cell count is reduced. A deficient red blood cell count can result in anemia, a condition where insufficient oxygen is delivered to the body’s organs and tissues. Anemia can be associated with CRF, both in patients on dialysis and not on dialysis. Anemia can also result from chemotherapy treatments for patients with non-myeloid malignancies. We were granted an exclusive license by Kirin-Amgen, Inc. (“KA”), a joint venture between Kirin Holdings Company, Limited (“Kirin”) and Amgen (see “Joint Ventures and Business Relationships ? Kirin Holdings Company, Limited”), to manufacture and market darbepoetin alfa in the United States, all European countries, Canada, Australia, New Zealand, Mexico, all Central and South American countries and certain countries in Central Asia, North Africa and the Middle East.
We market Aranesp(R) primarily in the United States and Europe. Aranesp(R) was initially launched in 2001 in the United States and Europe for the treatment of anemia associated with CRF (both in patients on dialysis and patients not on dialysis) and is also indicated for the treatment of CIA in patients with non-myeloid malignancies.
Worldwide Aranesp(R) sales for the years ended December 31, 2009, 2008, 2007 and 2006 were $2.65 billion, $3.1 billion, $3.6 billion and $4.1 billion, respectively. For the years ended December 31, 2009, 2008 and 2007, U.S. Aranesp@� sales were $1.25 billion, $1.65 billion and $2.15 billion, respectively and international Aranesp@� sales were $1.40 billion, $1.49 billion and $1.46 billion, respectively.
As a result of certain of the regulatory and reimbursement developments discussed above in the “Key Developments” section, worldwide Aranesp(R) sales and, in particular, sales in the U.S. supportive cancer care setting, have and will continue to be materially adversely affected.Our outstanding material patents for darbepoetin alfa are described in the table below. Territory General Subject Matter Expiration U.S. Glycosylation analogs of erythropoietin proteins 5/15/2024 Europe(1) Glycosylation analogs of erythropoietin proteins 10/12/2010 Europe(1) Glycosylation analogs of erythropoietin proteins 8/16/2014(1) In some cases, these European patents may also be entitled to supplemental protection in one or more countries in Europe and the length of any such extension will vary by country.Our principal European patent relating to Epoetin alfa expired on December 12, 2004. Although we do not market EPOGEN(R) in Europe, upon expiration of this patent, some companies have and other companies may receive approval for and market biosimilar or other products to compete with Aranesp(R) in Europe, presenting additional competition, as further discussed below.
Any products or technologies that are directly or indirectly successful in addressing anemia associated with chemotherapy and nephrology could negatively impact product sales of Aranesp(R). The following table reflects companies and their currently marketed products that primarily compete with Aranesp(R) in the United States and Europe in the supportive cancer care and nephrology segments, unless otherwise indicated.
Territory Competitor Marketed Product Competitor U.S. PROCRIT(R)(1) Centocor Ortho Biotech Products(2) Europe EPREXR/ERYPO(R) Janssen-Cilag(2) Europe NeoRecormon(R) Roche Europe Retacrit(TM)(3)/Silapo(R)(3) Hospira Enterprises B.V. (“Hospira”)/Stada Arzneimittel AG (“Stada”) Europe BinocritR(3)/Epoetin alfa Hexal(R)(3)/Abseamed(R)(3) Sandoz GmbH (“Sandoz”)/Hexal Biotech Forschungs GmbH (“Hexal”)/Medice Arzneimittel Putter GmbH & Company KG (“Medice”) Europe MIRCERA(R)(4) Roche Europe Dynepo(R)(5) Shire Pharmaceutical Group Plc (“Shire”) Europe Biopoin@� CT Arztneimittel GmbH ("CT Arztneimittel") (1) In the United States, Aranesp(R) competes with PROCRIT(R) in the supportive cancer care and pre-dialysis settings. (2) A subsidiary of J&J. (3) Biosimilar product approved and launched in certain EU countries. (4) Competes with Aranesp(R) in the nephrology segment only. (5) Shire announced in the second quarter of 2008 that it had decided to stop the commercialization of Dynepo(R).In the United States, Aranesp(R) also competes with EPOGEN(R), primarily in the U.S. hospital dialysis clinic setting. In addition to competition from the above-noted marketed products, the following product candidates could compete with Aranesp(R) in the future. Affymax Inc. (“Affymax”) and Takeda are co-developing Hematide?, an ESA for the treatment of anemia in renal patients. FibroGen is developing FG-2216 and FG-4592, orally active ESAs, for the treatment of anemia and is also studying FG-4592 for the treatment in anemia of chronic kidney disease (“CKD”). Ratiopharm is developing a biosimilar ESA, EpoTheta, expected to launch in the EU in 2009. Additionally, in December 2008, Merck & Company, Inc. (“Merck”) announced the formation of a new biotech division, Merck Bioventures, which is developing a late-stage pegylated ESA (MK-2578), which they have announced they expect to launch in 2012.【2009】 【2008】 【2006】Aranesp(R) is Amgen's registered trademark for one of its novel erythropoiesis stimulating proteins, a protein that stimulates red blood cell production. Red blood cells transport oxygen to all cells of the body. Without adequate amounts of erythropoietin, the red blood cell count is reduced. A deficient red blood cell count could result in anemia, a condition where insufficient oxygen is delivered to the body's organs and tissues. Anemia can be associated with chronic renal failure, both in patients on dialysis and not on dialysis. Anemia can also result from chemotherapy treatments for patients with non-myeloid malignancies. Aranesp(R) relieves anemia symptoms and reduces the need for blood transfusions. We were granted an exclusive license by Kirin-Amgen, Inc. (“KA”), a joint venture between Kirin Brewery Company, Limited (“Kirin”) and Amgen (see “Joint Ventures and Business Relationships - Kirin Brewery Company, Limited”) to manufacture and market darbepoetin alfa in the United States, Europe, Canada, Australia, New Zealand, Mexico, all Central and South American countries and certain countries in Central Asia, North Africa and the Middle East.
We primarily market Aranesp(R) in the United States and Europe. Darbepoetin alfa is also marketed under the brand name Nespo(R) in Italy. Aranesp(R) was initially launched in 2001 in the United States and Europe and is indicated for the treatment of anemia associated with chronic renal failure (both in patients on dialysis and patients not on dialysis) as well as for the treatment of chemotherapy-induced anemia in patients with non-myeloid malignancies. In March 2006, the FDA approved label changes to include every-three-week dosing of Aranesp(R) for the treatment of chemotherapy-induced anemia in patients with non-myeloid malignancies.
Worldwide Aranesp(R) sales for the years ended December 31, 2006, 2005 and 2004 were $4,121 million, $3,273 million and $2,473 million, respectively.
●ENBREL ENBREL is our registered trademark for our TNF receptor fusion protein that inhibits its binding to TNF receptors, which can result in a significant reduction in inflammatory activity. TNF is one of the chemical messengers that help regulate the inflammatory process. When the body produces too much TNF, it overwhelms the immune system’s ability to control inflammation of the joints or of psoriasis-affected skin areas. ENBREL is similar to a protein that the body produces naturally, and like this protein, it binds and deactivates certain TNF molecules before they can trigger inflammation. We acquired the rights to ENBREL in July 2002 as part of our acquisition of Immunex Corporation (“Immunex”).
We market ENBREL under a co-promotion agreement with Wyeth in the United States and Canada (see “Joint Ventures and Business Relationships ? Wyeth”). The rights to market ENBREL outside of the United States and Canada are reserved to Wyeth. ENBREL was initially launched in November 1998 by Immunex for the treatment of RA. In addition, ENBREL is now indicated for the treatment of adult patients with the following conditions: moderately to severely active RA; chronic moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy; active psoriatic arthritis and active ankylosing spondylitis. ENBREL is also approved for the treatment of moderately to severely active polyarticular-course juvenile RA in patients who have had an inadequate response to one or more disease-modifying medicines.
ENBREL sales for the years ended December 31, 2008, 2007 and 2006 were $3.6 billion, $3.2 billion and $2.9 billion, respectively.
Our outstanding material patents for etanercept are described in the table below. Territory General Subject Matter Expiration U.S. Methods of treating TNF ? dependent inflammatory response 9/5/2009 U.S. TNFR proteins and pharmaceutical compositions 9/5/2009 U.S. TNFR DNA vectors, cells and processes for making proteins 10/23/2012Any products or technologies that are directly or indirectly successful in treating rheumatology, which includes moderate to severe RA, moderate to severe juvenile RA and psoriatic arthritis; and dermatology, which includes ankylosing spondylitis and moderate to severe plaque psoriasis, could negatively impact product sales of ENBREL. Current treatments for these indications include generic methotrexate and other products, as further discussed below.The following table reflects companies and their currently marketed products that primarily compete with ENBREL in the United States and Canada in the inflammatory disease setting.
Territory Therapeutic Area Competitor/Marketed Product Competitor U.S. & Canada Rheumatology & Dermatology REMICADE(R) Centocor, Inc.(1)/Schering Plough Corporation U.S. & Canada Rheumatology & Dermatology HUMIRA(R) Abbott Laboratories (“Abbott”) U.S. & Canada Rheumatology & Dermatology Trexall(TM) Duramed Pharmaceuticals, Inc.(2) U.S. & Canada Rheumatology Orencia(R) Bristol-Myers Squibb Corporation (“BMS”) U.S. & Canada Rheumatology Arava(R) Sanofi-Aventis U.S. & Canada Rheumatology Rheumatrex(R) DAVA Pharmaceuticals, Inc. U.S. & Canada Rheumatology Rituxan(R) Genentech, Inc. (“Genentech”) U.S. & Canada Dermatology Raptiva(R) Genentech U.S. & Canada Dermatology Amevive(R) Biogen IDEC Inc. (“Biogen”) U.S. & Canada Dermatology Neoral(R) Novartis AG (“Novartis”) U.S. & Canada Dermatology Soriatane(R) Connetics Corporation(3) (1) A subsidiary of J&J. (2) A subsidiary of Barr Pharmaceuticals, Inc. (“Barr”) (3) A subsidiary of Stiefel Laboratories, Inc.In addition to competition from the above-noted marketed products, various companies are developing products which may compete with ENBREL in the future, including the following. In December 2007, J&J filed a BLA with the FDA and a market authorization application (“MAA”) with the EMEA for CNTO 1275 (ustekinumab) to treat adults with moderate to severe plaque psoriasis. Although the DODAC unanimously recommended CNTO 1275 for approval, in December 2008, the FDA declined approval and requested additional information from J&J. J&J is also developing CNTO 148 (golimumab) for the treatment of RA. Additionally, a number of companies have cytokine inhibitors in development, including GlaxoSmithKline plc (“GlaxoSmithKline”), Pfizer Inc. (“Pfizer”), Repligen Corporation and Taisho Pharmaceutical Co., Ltd. Roche filed a BLA for its RA candidate Actemra (tocilizumab) in November 2007 and received a complete response letter from the FDA in September 2008, requesting additional data on the labeling and manufacture of the drug. Abbott is developing ABT-874, which is a psoriasis drug, and is in phase 3 trials. UCB has partnered with Nektar Therapeutics to develop Cimzia(R) (PEGylated anti-TNF) for the treatment of RA. On January 5, 2009, the FDA issued a complete response letter relating to the BLA of Cimzia(R) for treatment of RA requesting additional information.【2009】 【2008】 【2008安全性問題】On March 17, 2008, we and Wyeth Pharmaceuticals, a division of Wyeth, announced updates to the FDA approved labeling for ENBREL, in which the U.S. PI now contains a boxed warning relating to the risk of infections, including tuberculosis. This information in the boxed warning includes additional language regarding screening and monitoring patients for tuberculosis, including patients who tested negative for latent tuberculosis infection. As part of this labeling update, the FDA also required the implementation of a REMS for ENBREL in the form of a medication guide. Additionally, following the FDA web-alert on September 4, 2008 regarding their review of histoplasmosis and other opportunistic fungal infections in patients treated with TNF-blockers, the FDA requested that the boxed warning and WARNINGS sections of the U.S. PI and the medication guide for ENBREL (and other TNF-blockers) be strengthened to include the risk of unrecognized histoplasmosis and other invasive fungal infections with the goal of increasing timely diagnosis and treatment. The FDA also requested that the approved REMS for ENBREL be modified with a communication plan to healthcare providers regarding the risk of unrecognized fungal infections. In December 2008, we agreed with the FDA on the required revisions to the U.S. PI, and we continue to work with the FDA to finalize the requested updates to the ENBREL REMS. In addition, there are several other outstanding regulatory matters that may also negatively impact future ENBREL product sales. For example, on June 4, 2008, the FDA issued an Early Communication regarding an ongoing safety review of TNF-blockers and the possible association between the use of these medicines and the development of lymphoma and other cancers in children and young adults and stated that it had decided to conduct further analyses to evaluate the risk and benefits of TNF-blockers in pediatric patients. Furthermore, following the June 18, 2008 Dermatologic and Ophthalmic Drugs Advisory Committee (“DODAC”) meeting, on July 24, 2008, we received notification from the FDA through a complete response letter that they would like additional information from us regarding the use of ENBREL in pediatric patients with chronic moderate to severe plaque psoriasis. We continue to work with the FDA to provide it with the above-noted requested information.
●Neulasta(R) (pegfilgrastim)/NEUPOGEN(R) (Filgrastim) Neulasta(R) is our registered trademark for a pegylated protein that selectively stimulates production of certain white blood cells known as neutrophils and is based on the Filgrastim molecule. Neutrophils defend against infection. NEUPOGEN(R) is our registered trademark for our recombinant-methionyl human G-CSF, a protein that also selectively stimulates production of neutrophils. Treatments for various diseases and diseases themselves can result in extremely low numbers of neutrophils, a condition called neutropenia. Myelosuppressive chemotherapy, one treatment option for individuals with certain types of cancers, targets cell types that grow rapidly, such as tumor cells. Normal cells that divide rapidly, such as those in the bone marrow that become neutrophils, are also vulnerable to the effects of cytotoxic chemotherapy, resulting in neutropenia with an increased risk of severe infection. Very often, neutropenia is the dose limiting side effect of chemotherapy and can thus be responsible for a reduction in the amount of chemotherapy that can be administered safely. Such reductions in chemotherapy dose can compromise the effectiveness of chemotherapy on the cancer it is being used to treat, with the result of a higher treatment failure rate. As mentioned above, the pegfilgrastim molecule is based on the Filgrastim molecule. A polyethylene glycol molecule (“PEG”) is added to enlarge the Filgrastim molecule, thereby extending its half-life and causing it to be removed more slowly from the body. Because pegfilgrastim is eliminated through binding to its receptor on neutrophils and their precursors, pegfilgrastim remains in the circulation until neutrophil recovery has occurred. This neutrophil-mediated clearance allows for administration as a single dose per chemotherapy cycle, compared with NEUPOGEN(R), which requires more frequent dosing. Neulasta(R) and NEUPOGEN(R) are prescribed more frequently in the curative setting, in which myelosuppressive chemotherapy is administered with the intent to cure cancer, rather than in the palliative setting, in which myelosuppressive chemotherapy is administered to treat other complications of cancer by managing tumor growth. We were granted an exclusive license to manufacture and market pegfilgrastim and G-CSF in the United States, Europe, Canada, Australia and New Zealand under a licensing agreement with KA (see “Joint Ventures and Business Relationships ? Kirin Holdings Company, Limited”).
We market Neulasta(R) and NEUPOGEN(R) primarily in the United States and Europe. Filgrastim is also marketed under the brand name GRANULOKINE(R) in Italy. Neulasta(R) was initially launched in the United States and Europe in 2002 and is indicated for reducing the incidence of infection associated with chemotherapy-induced neutropenia in cancer patients with non-myeloid malignancies. Administration of Neulasta(R) in all cycles of chemotherapy is approved for patients receiving myelosuppressive chemotherapy associated with at least a 17% risk of febrile neutropenia. NEUPOGEN(R) was initially launched in the United States and Europe in 1991. NEUPOGEN(R) is indicated for reducing the incidence of infection as manifested by febrile neutropenia for patients with non-myeloid malignancies undergoing myelosuppressive chemotherapy; reducing the duration of neutropenia and neutropenia-related consequences for patients with non-myeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation; reducing the incidence and duration of neutropenia-related consequences in symptomatic patients with congenital neutropenia, cyclic neutropenia or idiopathic neutropenia (collectively, severe chronic neutropenia); mobilizing peripheral blood progenitor cells (“PBPC”) in cancer patients who have undergone myeloablative chemotherapy for stem cell transplantation; and reducing the recovery time of neutrophils and the duration of fever following induction or consolidation chemotherapy treatment in adult patients with acute myeloid leukemia (“AML”).
Worldwide Neulasta(R) sales for the years ended December 31, 2008, 2007 and 2006 were $3.3 billion, $3.0 billion and $2.7 billion, respectively. Worldwide NEUPOGEN(R) sales for the years ended December 31, 2008, 2007 and 2006 were $1.3 billion, $1.3 billion and $1.2 billion, respectively.
Our outstanding material patents for pegfilgrastim are described in the table below. Territory General Subject Matter Expiration U.S. Pegylated G-CSF 10/20/2015 Europe(1) Pegylated G-CSF 2/8/2015(1) In some cases, this European patent may also be entitled to supplemental protection in one or more countries in Europe and the length of any such extension will vary by country.
Our outstanding material patents for Filgrastim are described in the table below. Territory General Subject Matter Expiration U.S. G-CSF polypeptides 12/3/2013 U.S. Methods of treatment using G-CSF polypeptides 12/10/2013Our principal European patent relating to G-CSF expired on August 22, 2006. Upon expiration of this patent, some companies have and other companies may receive approval for and market biosimilar products and other products to compete with Neulasta(R) and NEUPOGEN(R) in Europe, presenting additional competition, as further discussed below.Neulasta(R) and NEUPOGEN(R) could face competition in some circumstances from companies marketing or developing treatments for neutropenia associated with chemotherapy, for bone marrow and PBPC transplant patients, and AML. NEUPOGEN(R) competes with Neulasta(R) in the United States and Europe. U.S. and international NEUPOGEN(R) sales have been adversely impacted by conversion to Neulasta(R). However, we believe that the conversion in the United States is substantially complete and that a significant amount of the conversion in Europe had already occurred.
The following table reflects companies and their currently marketed products that primarily compete with Neulasta(R) and NEUPOGEN(R) in the United States and Europe in the supportive cancer care segment.
Territory Competitor Marketed Product Competitor U.S. Leukine(R) Bayer HealthCare Pharmaceuticals Europe Granocyte(R) Chugai Pharmaceuticals Co., Ltd./Sanofi-Aventis Europe RatiograstimR(1)/Filgrastim RatiopharmR(1) Ratiopharm Europe BiograstimR(1) CT Arzneimittel Europe TevagrastimR(2) Teva Europe ZarzioR(3)/Filgrastim HexalR(3) Sandoz/Hexal(1) Biosimilar products that received marketing authorization by the European Commission in September 2008 and launched in certain EU countries thereafter.
(2) Biosimilar product that received marketing authorization by the European Commission in September 2008 for which Teva has stated that it would begin marketing throughout Europe in 2009.
(3) Biosimilar products that received marketing authorization by the European Commission in February 2009.【2009】 【2008】 ●Sensipar(R) (cinacalcet) Sensipar(R) is our registered trademark in the United States and Mimpara(R) is our registered trademark in Europe, for our first small molecule medicine used in treating CKD patients on dialysis who produce too much parathyroid hormone, a condition known as secondary hyperparathyroidism. In 2004, SensiparR/Mimpara(R) was approved in the United States and Europe for the treatment of secondary hyperparathyroidism in CKD patients on dialysis and for the treatment of hypercalcemia in patients with parathyroid carcinoma. We market Sensipar(R)/Mimpara(R) primarily in the United States and Europe. Sensipar(R) sales for the years ended December 31, 2008, 2007 and 2006 were $597 million, $463 million and $321 million, respectively.
Our outstanding material patents for cinacalcet are described in the table below. Cinacalcet General Subject Matter Expiration U.S.(1) Calcium receptor-active molecules 10/23/2015 U.S.(1) Calcium receptor-active molecules 12/14/2016 U.S.(1) Methods of treatment 12/14/2016 Europe(2) Calcium receptor-active molecules 10/23/2015(1) An application for patent term extension has been submitted and is currently pending in the United States.
(2) In some cases, this European patent may also be entitled to supplemental protection in one or more countries in Europe and the length of any such extension will vary by country.Any products or technologies that are directly or indirectly successful in treating secondary hyperparathyroidism in patients with CKD on dialysis and/or hypercalcemia in patients with parathyroid carcinoma could negatively impact product sales of SensiparR/Mimpara(R).
The following table reflects companies and their currently marked products that primarily compete with Sensipar(R) in the United States and Mimpara(R) in Europe in the nephrology segment.
Territory Competitor Marketed Product Competitor U.S. Zemplar(R) Abbott U.S. Hectorol(R) Genzyme Corporation (“Genzyme”) U.S. Rocaltrol(R) Roche Europe Zemplar(R) Abbott Europe Renegel(R) Genzyme Europe Fosrenol(R) Shire Europe OsvaRen(R) Fresenius Medical CareOn July 25, 2008, we filed a lawsuit against Teva and Barr for infringement of four Sensipar(R) patents. The lawsuit is based on the Abbreviated New Drug Application (“ANDA”) filed by Teva and Barr which seeks approval to market generic versions of Sensipar(R). (See Note 10, “Contingencies” to the Consolidated Financial Statements.) These generic versions could compete with Sensipar(R) in the future.【2009】 ● 【2009】 (1) An application for patent term extension has been submitted and is currently pending in the U.S. (2) In some cases these European patents may also be entitled to supplemental protection in one or more countries in Europe and the length of any such extension will vary country by country
Product 国 General Subject Matter Expiration Epoetin alfa U.S. － Process of making erythropoietin 8/15/2012 － Product claims to erythropoietin 8/20/2013 － Pharmaceutical compositions of erythropoietin 8/20/2013 － Cells that make certain levels of erythropoietin 5/26/2015 darbepoetin alfa Europe(2) － Glycosylation analogs of erythropoietin proteins 10/12/2010 － Glycosylation analogs of erythropoietin proteins 8/16/2014 Filgrastim U.S. － G-CSF polypeptides 12/3/2013 － Methods of treatment using G-CSF polypeptides 12/10/2013 pegfilgrastim U.S. － Pegylated G-CSF 10/20/2015 Europe(2) － Pegylated G-CSF 2/8/2015 etanercept U.S. － Methods of treating TNF － dependent inflammatory response 9/5/2009 － TNFR proteins and pharmaceutical compositions 9/5/2009 － TNFR DNA vectors, cells and processes for making proteins 10/23/2012 panitumumab U.S. － Human monoclonal antibodies to EGFr 5/5/2017 cinacalcet HCl U.S.(1) － Calcium receptor-active molecules 12/14/2016 － Calcium receptor-active molecules 12/14/2016 － Calcium receptor-active molecules 12/14/2016 － Calcium receptor-active molecules 10/23/2015 Europe(2) － Calcium receptor-active molecules 10/23/2015
●Amgen ●Media Center ★Press Releases －★Abgenix Press Release Archives －★Tularik Press Release Archives －★Immunex Press Release Archives ●Medical Professionals ★Products ●Investors ★Pipeline ★Fact Sheet～四半期報告、SEC ★SEC Filings 10-K Annual Report 2009[2010.3.01] - [pdf] - [doc] - [xls] 10-K Annual Report 2008[2009.2.27] - [pdf,358p] - [doc] 10-K Annual Report 2007[2008.2.28] - [pdf,213p] 10-K Annual Report 2006[2007.2.28] - [pdf,149p] 10-K Annual 2005[2006.3.10] - [pdf,319p] - [xls] 10-K Annual 2004[2005.3.9] - [pdf,140p]| [xls]| [doc] ★Annual reports Annual Report and 10-K[2009.3.17;pdf,190p] Annual Report 2006 - [pdf,38p] Annual 2004 10-K[pdf,124p] Annual Report 2004[pdf,38p] - Online版 Annual Report 2003 Annual Report 2002 Annual Report 2001 Amgen's Fourth Quarter 2006 Revenue Increased 17% to $3.8 Billion; Full Year 2006 Revenue Increased 15% to $14.3 Billion[2007.1.25] Amgen's Fourth Quarter 2003 Adjusted Earnings Per Share Increased 31 Percent to 46 Cents[pdf-11p,2004.1.22] AMGEN REPORTS FOURTH QUARTER AND FULL YEAR 2001 FINANCIAL RESULTS IN LINE WITH GUIDANCE[2002.1.23] On An Adjusted Basis, Amgen Repor