MLリソース：仮性球情動
Nuedexta, pseudobulbar affect, PBA, 制御不能情動,仮性球情動,仮性球麻痺情動,偽性球麻痺の情動失禁,仮性球麻痺に起こる制御不能の情動Supported by Nobelpharma Co.Ltd.
in a part.
■個別収録製品[1366]●デキストロメトルファン／キニジンDextromethorphan hydrobromide/Quinidine sulfate(Nuedexta - Avanir)
日本語版註）デキストロメトルファン／キニジンDextromethorphan hydrobromide/Quinidine sulfate(Nuedexta - Avanir)
【日本語版コメント1366～仮性球情動治療薬デキストロメトルファン／キニジン(Nuedexta - Avanir)】
【別名】AVP-923;旧Zenvia 【開発元】Avanir Pharmaceuticals,Inc. [DBR_ID]
【化学名】
【承認】FDA申請=27-Jan-2006、FDA承認=29-Oct-2010、米国発売31-Jan-2011 ; 【製剤】Capsules:ﾙ� Dextromethorphan hydrobromide 20 mg and Quinidine sulfate 10 mg 【適応】(仮性球情動の治療) NUEDEXTA is a combination product containing dextromethorphan hydrobromide (an uncompetitive NMDA receptor antagonist and sigma-1 agonist) and quinidine sulfate (a CYP450 2D6 inhibitor) indicated for the treatment of pseudobulbar affect (PBA). Studies to support the effectiveness of NUEDEXTA were performed in patients with underlying amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). NUEDEXTA has not been shown to be safe or effective in other types of emotional lability that can commonly occur, for example, in Alzheimerkﾋs disease and other dementias. 【用法用量】初回１日１カプセルを１週間。 維持量は１週後、１２時間毎に１カプセル
【作用】Dextromethorphan (DM) is a sigma-1 receptor agonist and an uncompetitive NMDA receptor antagonist. Quinidine increases plasma levels of dextromethorphan by competitively inhibiting cytochrome P450 2D6, which catalyzes a major biotransformation pathway for dextromethorphan. The mechanism by which dextromethorphan exerts therapeutic effects in patients with pseudobulbar affect is unknown. 【特徴】
【製品情報】www.nuedexta.com 【添付文書】Nuedexta-PI
【提携】 【EU】申請準備中
【日本】未開発 【その他】
仮性球情動(Pseudobulbar affect:PBA)とは、情緒不安, 不安定な情動または情動失禁に代表される神経障害で、不随意に泣き叫んだり、コントロールできない泣き笑いなどの情動を発現する。 ALSやMS等の神経疾患または脳損傷により二次的に起こる。 推定PBA有病率は、米国だけに150～200万人。 脳卒中患者の28%～52%、MS患者の約10%、ALS患者の49%、外傷性脳損傷(TBI)患者の5%が疫学上のPBA罹患率。 従来の治療法としては抗うつ薬が使用されることが多い。 2010年10月29日に、デキストロメトルファンとキニジン配合剤が米国食品医薬品局(FDA)によりPBA治療薬として承認された。 この薬剤NuedextaはAvanir Pharmaceuticalsにより開発され、2011年1月31日で発売された。
【市場】 【開発中の新薬】 ●「治験」ホームページ[厚生労働省] - 開発中の新薬[＜情報提供：日本製薬工業協会＞] 会社別開発中新薬一覧。 検索機能なし。７９社から情報提供●New Medicines in Development[PhRMA 米製薬協]
治験薬記号(一般名)
および剤型予定される効能又は効果、
対象疾患名および症状名開発段階 その他 国内 海外 (地域) from Wolters Kluwer Health's Adis R&D Insight 【解説資料】 ●メルクマニュアル第18版日本語版 運動ニューロン疾患 多発性硬化症 (MS) ●Pseudobulbar affect -Wikipedia ● 【データ】 ●Pseudobulbar Affect (PBA) Survey Results Released[06-Jan-2011]by the Brain Injury Association of America (BIAA) ●医療用医薬品添付文書
Registered Name Company Status Indication 備考 米 【臨床ガイドライン】 ●MINDS 医療情報サービス：診療ガイドライン[日本医療機能評価機構] - 該当なし ●診療ガイドライン[東邦大学医学メディアセンター] 該当なし ●National Guideline Clearinghouse - 米国
製品 組成 適応症 用法用量 備考 []
発売[]
発売[]
発売
Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: multidisciplinary care, symptom management, and cognitive/behavioral impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 73(15)1227-1233(13-Oct-2009)
American Academy of Neurology; 全文; 日本語翻訳(13-21p)
エビデンスに基づく筋萎縮性側索硬化症（ALS）のケア[MTPro 2010 年5 月13 日]
●CMA Infobase -Clinical Practice Guidelines -カナダ Cnadian Medical Association ●NICE - Clinical Guidelines by 英国NHS [National Health Service] ●Scottish Medicines Consortium[SMC] - NHS Scotlandの一部門 - Medicines ●Primary Care Clinical Practice Guidelines by UCSF個人ベース ●ACP-ASIM: Guidelines ●AAFP: Clinical Recommendations by 米国家庭医学会 ●ICSI - Institute for Clinical Systems Improvement by 民間ベース () 【総説記事・文献】 Review of Pseudobulbar Affect Including a Novel and Potential Therapy J Neuropsychiatry and Clinical Neurosciences 2005; 17:447kｿ454 【ニュース・トピックス】 【リンク・リソース】 【主要サイト】 PBAinfo.org - http://www.pbainfo.org/
●解説
●データ
●臨床ガイドラインなど
●総説記事・文献
●ニュース・トピックス
●リンク＆リソース
●主要サイト
[1366]●製品 デキストロメトルファン／キニジンDextromethorphan hydrobromide/Quinidine sulfate(Nuedexta - Avanir)
日本語版註）デキストロメトルファン／キニジンDextromethorphan hydrobromide/Quinidine sulfate(Nuedexta - Avanir)
【別名】AVP-923;旧Zenvia 【開発元】Avanir Pharmaceuticals,Inc. [DBR_ID]
【化学名】
【承認】FDA申請=27-Jan-2006、FDA承認=29-Oct-2010、米国発売31-Jan-2011 ; 【製剤】Capsules:ﾙ� Dextromethorphan hydrobromide 20 mg and Quinidine sulfate 10 mg 【適応】(仮性球情動の治療) NUEDEXTA is a combination product containing dextromethorphan hydrobromide (an uncompetitive NMDA receptor antagonist and sigma-1 agonist) and quinidine sulfate (a CYP450 2D6 inhibitor) indicated for the treatment of pseudobulbar affect (PBA). Studies to support the effectiveness of NUEDEXTA were performed in patients with underlying amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). NUEDEXTA has not been shown to be safe or effective in other types of emotional lability that can commonly occur, for example, in Alzheimerkﾋs disease and other dementias. 【用法用量】初回１日１カプセルを１週間。 維持量は１週後、１２時間毎に１カプセル
【作用】Dextromethorphan (DM) is a sigma-1 receptor agonist and an uncompetitive NMDA receptor antagonist. Quinidine increases plasma levels of dextromethorphan by competitively inhibiting cytochrome P450 2D6, which catalyzes a major biotransformation pathway for dextromethorphan. The mechanism by which dextromethorphan exerts therapeutic effects in patients with pseudobulbar affect is unknown. 【特徴】
【製品情報】www.nuedexta.com 【添付文書】Nuedexta-PI
【提携】 【EU】申請準備中
【日本】未開発 【その他】
★
★1366★27/12★11.06.13★046★仮性球情動治療薬デキストロメトルファン／キニジン(Nuedexta - Avanir)/2p●MLリソース:仮性球情動
【日本語版コメント1366～仮性球情動治療薬デキストロメトルファン／キニジン(Nuedexta - Avanir)】
仮性球情動(Pseudobulbar affect:PBA)とは、情緒不安, 不安定な情動または情動失禁に代表される神経障害で、不随意に泣き叫んだり、コントロールできない泣き笑いなどの情動を発現する。 ALSやMS等の神経疾患または脳損傷により二次的に起こる。 推定PBA有病率は、米国だけに150～200万人。 脳卒中患者の28%～52%、MS患者の約10%、ALS患者の49%、外傷性脳損傷(TBI)患者の5%が疫学上のPBA罹患率。 従来の治療法としては抗うつ薬が使用されることが多い。 2010年10月29日に、デキストロメトルファンとキニジン配合剤が米国食品医薬品局(FDA)によりPBA治療薬として承認された。 この薬剤NuedextaはAvanir Pharmaceuticalsにより開発され、2011年1月31日で発売された。→詳細は参考資料●MLリソース:仮性球情動に纏めた。＜日本語版コメント要約＞
・鎮咳薬のデキストロメトルファン臭化水素酸塩と抗不整脈薬キニジン硫酸塩の配合剤Nuedextaが、仮性球情動の経口治療薬として承認された。
・仮性球情動は病的な泣き笑いや情動不安定を特徴とし、筋萎縮性側索硬化症や多発性硬化症患者によく見られる。
・重度の仮性球情動のある筋萎縮性側索硬化症患者、多発性硬化症患者において、本剤は症状を50%減少させた。
・本適応症において、Nuedextaと他の薬剤との比較は行われていない。
●承認データ：FDA ●FDA Newsroom - FDA Press Releases ●Index to Drug-Specific Information ●2004.5.1 以降 Drugs@FDA
★Drug Name(s) =Nuedexta (DEXTROMETHORPHAN HYDROBROMIDE; QUINIDINE SULFATE) FDA Application No. =(NDA) 021879 Active Ingredient(s)=dextromethorphan hydrobromide and quinidine sulfate Company =Avanir Pharmaceuticals Dosage Form/Route =CAPSULE; ORAL 20MG;10MG Strength = - Approval Date=10/29/2010[000][Approval]:Label[添付文書]|Letter[承認書]|Review|Summary Review 申請January 27, 2006 適応for the treatment of pseudobulbar affect (PBA). Original Approval or Tentative Approval Date:October 29, 2010 Chemical Type: 4 New combination Review Classification: P Priority review drug
●Electronic Orange Book Application Number: N021879 Active Ingredient : DEXTROMETHORPHAN HYDROBROMIDE; QUINIDINE SULFATE Proprietary Name : NUEDEXTA [AVANIR PHARMS] CAPSULE; ORAL 20MG;10MG Approval Date : Oct 29, 2010 Exclusivity Data : NC Oct 29, 2013 Patent Data : 5166207 Jun 17, 2011 U - 1093 5206248 Mar 27, 2012 U - 1093 7659282 Aug 13, 2026 U - 1093 RE38115 Jan 26, 2016 Y
●EU承認 ●ema - Human Medcines ●List of Authorized Products (EPARs)★[A-Z 承認品目] 該当なし
●Avanir Pharmaceuticals,Inc. - http://www.avanir.com/ ;(Nasdaq: AVNR);20 Enterprise, Suite 200,Aliso Viejo, CA 92656 a biopharmaceutical company focused on acquiring, developing, and commercializing novel therapeutic products for the treatment of central nervous system disorders 1988年08月 Californiaで設立。 ■Products NUEDEXTA™(dextromethorphan hydrobromide and quinidine sulfate) abreva® (docosanol 10% cream) - HSV1 - GSKから北米販売権をライセンス ★Product pipeline AVP-923 P3 for Diabetic Peripheral Neuropathic Pain Xenerex 前臨床 from Novartis MIF Inhibitor 前臨床 from Emergent BioSolutions - Avanir has licensed macrophage migration inhibitory factor (MIF) program to Novartis International Pharmaceutical Ltd. and has sold its anthrax monoclonal antibody program to Emergent BioSolutions ■Investors ●Financial Reports 2010 Annual Report[2010.9.30] ●SEC Filings 10-K Annual Report[2010.12.8] - [pdf] - [doc] - [xls] 10-K Annual Report[2009.11.25] - [pdf] - [doc] - [xls] 10-K Annual Report[2008.12.17] - [pdf] - [doc] - [xls] ●Press Releases Avanir Pharmaceuticals Files Lawsuits Against Par and Actavis for Infringement of NUEDEXTA Patents[2011.8.11]
Avanir Pharmaceuticals Provides Update on European Regulatory Filing for NUEDEXTA[2011.7.26]
Avanir Pharmaceuticals Announces Paragraph IV ANDA Filing for NUEDEXTA[2011.7.1] - GEが2011.3.7に申請された。
Avanir Pharmaceuticals Announces Landmark 'PRISM' Pseudobulbar Affect Patient Registry[2011.5.4]～推定200万人の患者。 １万人を目標
AVANIR Pharmaceuticals Announces U.S. Launch and Availability of NUEDEXTA™ for Pseudobulbar Affect[2011.1.31]
AVANIR Pharmaceuticals Announces FDA Approval of NUEDEXTA™ [2010.10.29]
AVANIR Submits Expanded Neurodex New Drug Application For The Treatment Of Involuntary Emotional Expression Disorder[2006.1.30]
●会社決算
($ ) 2010/9 2009/9 2008/9 2007/9 2006/9 2005/9 売上高 2,895,474 4,176,509 6,958,568 9,224,561 15,185,852 営業経費 29,794,558 26,017,815 24,709,901 33,945,900 59,369,701 営業利益 (27,096,724) (21,924,665) (18,962,458) (29,368,855) (51,677,459) 経常利益 当期純利益 (26,694,148) (21,996,016) (17,495,739) (20,933,453) (62,552,814) 研究開発費 13,322,040 15,867,049 14,110,743 従業員数[連結] 128
●NUEDEXTA for the treatment of PBA 【2010】
NUEDEXTA TM is the first and only FDA-approved treatment for PBA, which occurs secondary to a variety of otherwise unrelated neurological conditions, and is characterized by involuntary, sudden, and frequent episodes of laughing and/or crying. PBA episodes typically occur out of proportion or incongruent to the patient’s underlying emotional state.NUEDEXTA is an innovative combination of two well-characterized components: dextromethorphan hydrobromide (20 mg), the ingredient active in the central nervous system, and quinidine sulfate (10 mg), a metabolic inhibitor enabling therapeutic dextromethorphan concentrations. NUEDEXTA acts on sigma-1 and NMethyl- D-aspartic acid, or NMDA, receptors in the brain, although the mechanism by which NUEDEXTA exerts therapeutic effects in patients with PBA is unknown.
Studies to support the effectiveness of NUEDEXTA in PBA were performed in patients with amyotrophic lateral sclerosis, or ALS, and multiple sclerosis, or MS. NUEDEXTA has not been shown to be safe and effective in other types of emotional lability that can commonly occur, for example, in Alzheimer’s disease and other dementias. The primary outcome measure, laughing and crying episodes, was significantly lower in the NUEDEXTA cohort compared to placebo. The secondary outcome measure, the Center for Neurologic Studies Lability Scale (CNS-LS), demonstrated a significantly greater mean decrease in CNS-LS score from baseline for the NUEDEXTA cohort compared to placebo.
NUEDEXTA safety information
NUEDEXTA can interact with other medications causing significant changes in blood levels of those medications and/or NUEDEXTA. NUEDEXTA is contraindicated in patients receiving drugs that both prolong QT interval and are metabolized by CYP2D6 (e.g., thioridazine and pimozide) and should not be used concomitantly with other drugs containing quinidine, quinine, or mefloquine. NUEDEXTA is contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days. NUEDEXTA is contraindicated in patients with a known hypersensitivity to its components.
NUEDEXTA may cause serious side effects, including possible changes in heart rhythm. NUEDEXTA is contraindicated in patients with a prolonged QT interval, congenital long QT syndrome or a history suggestive of torsades de pointes, in patients with heart failure as well as patients with, or at risk of, complete atrioventricular (AV) block, unless the patient has an implanted pacemaker. NUEDEXTA causes dose-dependent QTc prolongation. When initiating NUEDEXTA in patients at risk of QT prolongation and torsades de pointes, electrocardiographic (ECG) evaluation of QT interval should be conducted at baseline and 3-4 hours after the first dose.
The most common adverse reactions in patients taking NUEDEXTA are diarrhea, dizziness, cough, vomiting, weakness, swelling of feet and ankles, urinary tract infection, flu, elevated liver enzymes, and flatulence.
NUEDEXTA may cause dizziness. Precautions to reduce the risk of falls should be taken, particularly for patients with motor impairment affecting gait or a history of falls.
PBA indication and market
PBA is a distinct neurologic syndrome that is characterized by a lack of control of emotional expression, typically involving episodes of involuntary or exaggerated motor expression of emotion such as laughing, crying or other emotional displays.
There are an estimated 18 to 20 million people in the United States who suffer from the underlying neurological conditions that can give rise to PBA. These underlying neurologic conditions include but are not limited to ALS, MS, Alzheimer’s disease, Parkinson’s disease, stroke and traumatic brain injury. Extrapolating from the epidemiologic medical literature, physician estimates and an AVANIR-sponsored patient survey, which surveyed a total of 2,464 patients and caregivers of patients with underlying neurologic conditions associated with PBA (including ALS, Alzheimer’s disease/dementias, MS, Parkinson’s disease, stroke and traumatic brain injury), we estimate that approximately 10% of people in the United States who suffer from neurological disease or injury suffer from moderate to severe PBA, with many more suffering from mild PBA.
Other than NUEDEXTA, there are no approved therapies indicated to treat PBA. Currently, some physicians treat PBA using a range of drugs off-label, including: selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors, or SSRIs/SNRIs, antidepressants and atypical antipsychotics. According to our market research, physicians are generally only moderately satisfied with these off-label therapies as a treatment for PBA. We conducted this market research through an Internet-based survey of 215 physicians, consisting of Neurologists, Internal Medicine/Geriatrics, Psychiatrists and Physical Medicine and Rehabilitation specialists.
We believe that NUEDEXTA represents a more attractive treatment option for patients suffering from PBA. In our Phase III STAR trial that was completed in 2009 with patients suffering from either ALS or MS as the underlying neurological condition, patients treated with NUEDEXTA reported an average overall 80% reduction in episodes at the end of the 12-week study compared to baseline, with an average 50% reduction in episodes in the first week of treatment. Over the course of the 12-week study, patients receiving NUEDEXTA experienced significantly lower PBA episode rates versus placebo ( P<0.0001 ). Over the final two weeks of the STAR trial, one-half of patients treated with NUEDEXTA achieved episode-free remission.
Our market research, conducted pursuant to the physician survey described above, indicates that 85% of surveyed physicians within targeted physician specialties would likely or very likely prescribe NUEDEXTA to treat their patients suffering from PBA. Of the surveyed physicians, the highest use was expected to be in PBA patients who have underlying conditions of either stroke or traumatic brain injury, but physicians expect to treat all PBA patient populations with NUEDEXTA. Among those physicians expressing an intent to prescribe NUEDEXTA, 78% indicated that NUEDEXTA would likely be used as a first-line therapy or an add-on therapy.
NUEDEXTA Commercialization Strategy
We intend to market NUEDEXTA initially to approximately 14,000 physicians who primarily specialize in psychiatry and neurology. Our commercialization strategy for NUEDEXTA includes the following elements: increase awareness of PBA, promote trial and adoption of NUEDEXTA, increase brand awareness of NUEDEXTA and minimize payment and distribution barriers.
【2010 Competition】
NUEDEXTA for Pseudobulbar Affect. Although NUEDEXTA is the first product to be marketed for the treatment of PBA, we are aware that physicians may prescribe other products in an off-label manner for the treatment of this disorder. For example, NUEDEXTA may face competition from the following products:
・Antidepressants, including Prozac ® , Celexa ® , Zoloft ® , Paxil ® , Elavil ® and Pamelor ® and others;
・Atypical antipsychotic agents, including Zyprexa ® , Risperdal ® , Seroquel, Abilify ® , Geodon ® and others; and
・Miscellaneous agents, including Symmetrel ® , Lithium and others.
While it is also possible that compounding pharmacies could combine the components of NUEDEXTA in an unauthorized fashion, it is inconsistent with the policies of the Pharmacy Compounding Accreditation Board.●NUEDEXTA(AVP-923) for the Treatment of Neuropathic Pain Indications 【2010】
AVP-923 for the treatment of diabetic neuropathic painDiabetic peripheral neuropathic pain (“DPN pain”), which arises from nerve injury, can result in a chronic and debilitating form of pain that has historically been poorly diagnosed and treated. It is often described as burning, tingling, stabbing, or pins and needles in the feet, legs, hands or arms. An estimated 3.5 million people in the United States experience DPN pain according to the American Diabetes Association. DPN pain currently is most commonly treated with antidepressants, anticonvulsants, opioid analgesics and local anesthetics. Most of these treatments have limited effectiveness or undesirable side effects resulting in a high degree of unmet medical need.
The neuropathic pain market is continuing to grow rapidly, and in 2006, was estimated to be worth $2.6 billion in sales among the seven largest markets, consisting of the United States, Japan, France, Germany, Italy, Spain and the United Kingdom.AVANIR has successfully completed a Phase III clinical trial for AVP-923 in the treatment of patients with DPN pain. In April 2007, we announced positive top-line data from our first Phase III clinical trial of AVP-923 for the treatment of patients with DPN pain. The primary endpoint of the trial was based on the daily diary entries for the Pain Rating Scale as defined in the SPA with the FDA. In the trial, two doses of AVP-923, 45/30 mg DMQ dosed twice daily (“AVP-923 45/30”) and 30/30 mg DMQ dosed twice daily (“AVP-923 30/30”), were compared to placebo based on daily patient diary entries for the Pain Rating Scale. Both AVP-923 treatment groups had lower pain ratings than placebo patients (p <0.0001 in both cases). In the AVP-923 45/30 patient group, average reductions were significantly greater than placebo patients at Days 30, 60, and 90 (p <0.0001 at each time point). In the AVP-923 30/30 patient group, average reductions were also significantly greater than placebo patients at Days 30 and 60 (p <0.0001) and Day 90 (p=0.007).
AVP-923 also demonstrated statistically significant improvements in a number of key secondary endpoints including the Pain Relief Ratings Scale and the Pain Intensity Ratings Scale. The secondary endpoints compared the baseline value to the average rating values at each study visit after randomization. The average pain relief reductions, as measured on the Pain Relief Rating Scale, were greater for the AVP-923 45/30 patient group (p=0.0002) and for the AVP-923 30/30 patient group (p=0.0083), compared with placebo. In addition, the DMQ 45, but not the DMQ 30, patient group demonstrated statistically significant improvements in the Pain Intensity Rating Scale compared with placebo (p=0.029). Although not powered to detect differences in the secondary endpoint of the Peripheral Neuropathy Quality of Life Scale Composite score and thus not achieving statistical significance, the AVP-923 45/30 patients showed a greater improvement than placebo patients (p=0.05) and the AVP-923 30/30 patients showed a trend towards greater improvement than placebo patients (p=0.08).
The most commonly reported adverse events from this Phase III study were dizziness, nausea, diarrhea, fatigue and somnolence, which were mild to moderate in nature. A higher number of patients in the AVP-923 45/30 and AVP-923 30/30 treatment groups (25.2% and 21.0%, respectively) discontinued due to an adverse event than compared to placebo (11.4%). There were no statistically significant differences in serious adverse event with 7.6%, 4.8% and 4.1% reported in the AVP-923 45/30, AVP-923 30/30 and placebo groups, respectively, and no deaths occurred during the study.
Due to safety concerns raised by the FDA in our October 2006 approvable letter for AVP-923, we conducted a formal pharmacokinetic (“PK”) study to identify a lower quinidine dose formulation that may have similar efficacy to the doses tested in the Phase III study. In May 2008, we reported a positive outcome of the formal PK study and announced that we identified alternative lower quinidine dose formulations of AVP-923 for the next DPN pain phase III clinical trial. The new dose is intended to deliver similar efficacy and improved safety/tolerability versus the formulations previously tested in DPN pain.
In September 2008, we submitted our Phase III protocol and related program questions for AVP-923 in the treatment of patients with DPN pain to the FDA under the SPA process. In subsequent communications regarding the continued development of AVP-923 for DPN pain, the FDA has indicated that it may be necessary to test a lower quinidine dose formulation in the DPN pain indication, such as the formulation that was identified in our PK study.
Additionally, based on feedback from the FDA, we believe that it is likely that two large well controlled Phase III trials utilizing a new lower quinidine dose formulation would be needed to support a New Drug Application (“NDA”) filing for this indication. Due to our limited capital resources and focus on the commercialization of NUEDEXTA, we do not expect that we will be able to initiate the trials needed for this indication without additional capital or a development partner for AVP-923. Accordingly, we are evaluating our options to fund this program, including the potential for a development partner.AVP-923 for the Treatment of MS Pain
In September 2009, we reported on secondary efficacy endpoints from the double-blind phase of the AVP-923 STAR trail in PBA, including an endpoint measuring reduction of pain in patients with underlying MS. AVP-923 30/10 mg demonstrated statistically significant relief of MS-related pain compared to placebo in the subset of MS patients with moderate-to-severe pain. Based on these data and the previous proof of concept pain data in MS patients with PBA, we are conducting a strategic assessment of the optimal clinical development path for AVP-923 to obtain an MS pain indication.
【2010 Competition】
AVP-923 for DPN pain. We anticipate that AVP-923 for the treatment of DPN pain, if further developed by us and approved by the FDA for marketing, would compete with other drug products that are currently prescribed by physicians, including those identified below. Additionally, many other companies are developing drug candidates for this indication and we expect competition for AVP-923, if approved to treat DPN pain, to be intense. Current approved competitors include: ・Cymbalta ® ;・Lyrica ® ;・Narcotic products; and ・Off-label uses of non-narcotic products, such as the anticonvulsants phenytoin, carbamazepine and topamax,and the antidepressant amitriptyline.
●Docosanol 10% Cream － Cold Sore Treatment 【2010】
Docosanol 10% cream is a topical treatment for cold sores. In 2000, we received FDA approval for marketing docosanol 10% cream as an over-the-counter product. Since that time, docosanol 10% cream has been approved by regulatory agencies in Asia, North America, and Europe. In March 2000, we granted a subsidiary of GlaxoSmithKline, SB Pharmco Puerto Rico, Inc. (“GSK”), the exclusive rights under a license to market docosanol 10% cream in the United States and Canada (“GSK License Agreement”). GSK markets the product under the name Abreva ® in these markets. Under the terms of the GSK License Agreement, GSK is responsible for all sales and marketing activities and the manufacturing and distribution of docosanol 10% cream. Under the GSK license agreement, the Company received a total of $25 million in milestone payments from GSK and the Company was entitled to receive an 8% royalty on net sales of Abreva by GSK.In November 2002, the Company sold to Drug Royalty USA an undivided interest in the Company’s rights to receive future Abreva royalties under the GSK License Agreement for $24.1 million (the “Drug Royalty Agreement”). Under the Drug Royalty Agreement, Drug Royalty USA has the right to receive royalties from GSK on sales of Abreva until December 2013. The Company retained the right to receive 50% of all royalties (a net of 4%) under the GSK License Agreement for annual net sales of Abreva in the U.S. and Canada in excess of $62 million. From the effective date of the GSK License Agreement up to the 2002 sale of the Company’s royalty rights to Drug Royalty USA, Inc. (“DRC”) the Company received a total of approximately $5.9 million in royalty payments from GSK attributed to the 8% royalty on net sales by GSK.
Under the terms of our docosanol license agreements, our partners are generally responsible for all regulatory approvals, sales and marketing activities, and manufacturing and distribution of the product in the licensed territories. The terms of the license agreements typically provide for us to receive a data transfer fee, potential milestone payments and royalties on product sales. We purchase the active pharmaceutical ingredient (“API”), docosanol, from a large supplier in Western Europe and have, on occasion, sold material to our licensees. We currently store our API in the United States. Any material disruption in manufacturing could cause a delay in shipments and possible loss of sales.
【2010 Competition】
Docosanol 10% cream. Abreva faces intense competition in the U.S. and Canada from the following established products:
・Over-the-counter preparations, including Carmex ® , Zilactin ® , Campho ® , Orajel ® , Herpecin ® and others;
・Zovirax ® acyclovir (oral and topical) and Valtrex ® valacyclovir (oral) prescription products marketed by Biovail Corporation and GSK, respectively; and
・Famvir ® famciclovir (oral) and Denavir ® penciclovir (topical) prescription products marketed by Novartis.●Xenerex Human Antibody Technology － Anthrax/Other Infectious Diseases 【2010】
In March 2008, we entered into an Asset Purchase and License Agreement with Emergent Biosolutions for the sale of our anthrax antibodies and license to use our proprietary Xenerex Technology platform, which was used to generate fully human antibodies to target antigens. Under the terms of the Agreement, we completed the remaining work under our NIH/NIAID grant (“NIH grant”) and transferred all materials to Emergent. Under the terms of the agreement, we are eligible to receive milestone payments and royalties on any product sales generated from this program. In connection with the sale of the anthrax antibody program, we also ceased all ongoing research and development work related to other infectious diseases on June 30, 2008.In September 2008, we entered into an Asset Purchase Agreement with a San Diego based biotechnology company for the sale of our non-anthrax related antibodies as well as the remaining equipment and supplies associated with the Xenerex Technology platform. In connection with this sale, we received an upfront payment of $210,000 and are eligible to receive future royalties on potential product sales, if any.
● 【2010】
株式会社メドレット Medlet Japan KK
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tel.03-3664-2020 fax.03-3666-3188 URL:www.medmk.com/mm/ E-Mail: support@medmk.com
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- 作成：2011.7.24 最終更新:2011.9.28 小菅博之
The Medical Letter日本語版
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On Drugs and Therapeutics
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