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                您當前位置:網站首頁 >> 醫藥新聞 >> 新藥上市 >> 2017年4月FDA批準上市新藥氘代丁苯那嗪DEUTETRABENAZINE
               
               
              2017年4月FDA批準上市新藥氘代丁苯那嗪DEUTETRABENAZINE
              2017-04-10 07:37:12 來源:有機化學網 瀏覽:13152


              商品名:Austedo
              通用名:Deutetrabenazine
              CAS:1392826-25-3
              物性:氘代丁苯那嗪(6個氫原子被氘原子代替),白色至淡黃色結晶性粉末,微溶于水,可溶于乙醇。
              原研:Teva
              代號:SD-809
              批準日期:2017年4月3日
              適應癥:亨廷頓舞蹈癥(Chorea associated with Huntington’s disease)
              劑型和規格:片劑,6mg、9mg、12mg
              用法用量:食物同服,整片吞服,推薦起始劑量6mg/d,每隔一周可增加6mg,劑量12mg/d以上時,分兩次服用,最大劑量48mg/d。
              作用機制:確切機理未明確,神經遞質以囊泡的形式貯存在神經元中,某些神經遞質的貯存,則是由囊泡單胺轉運體所控制的,Austedo是一種靶向囊泡單胺轉運體 2(vesicular monoamine transporter 2,VMAT-2)抑制劑,消耗機體單胺的儲存,減少單胺對突觸小泡的攝取。
              處方組成:Austedo的活性成分為Deutetrabenazine;非活性成分包括氨水、氧化鐵黑、正丁醇、BHA、BHT、硬脂酸鎂、甘露醇、微晶纖維素、PEG、PEO、吐溫80、丙二醇等。
              說明書:
              https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208082s000lbl.pdf
              亨廷頓氏舞蹈癥是一種顯性遺傳型疾病,由基因突變或第四對染色體內DNA基質之CAG三核甘酸重復序列過度擴張,引起的嚴重神經退行性疾病。“舞蹈病癥狀”是亨廷頓舞蹈癥最顯見的癥狀,近90%的亨廷頓患者在患病時期都會出現包括上下肢、面部或軀體的抽搐和不自主運動等。
              Austedo的有效性效和安全性是在隨機、雙盲、安慰劑對照的多中心3期臨床試驗中進行評估的,該試驗在90例明顯展示與亨廷頓舞蹈癥相關的“舞蹈病癥狀”的患者中進行。從基線到維護期(第9周和第12周的平均數據),接受Austedo治療患者的Total Maximal Chorea Scores評分指標提高約4.4個單位,而安慰劑組僅為約1.9個單位;這2.5單位的治療效果具有統計學意義(p<0.0001)。臨床研究包括NCT01897896、NCT02198794、NCT02195700等。
              Austedo最初是由Auspex開發,2015年3月,其三期臨床數據發表的4個月后,TeVa耗資32億美元收購Auspex。
              Austedo是第二個用于亨廷頓舞蹈癥的藥物(第一個丁苯那嗪,Tetrabenazine,商品名Xenazine)。也是FDA批準的全球首個氘代藥物,氘代可以使藥物在患者體內的代謝更為緩慢,藥物的半衰期延長。采用這種方式,用較低劑量即可獲得更大的療效。此前FDA授予孤兒藥資格,也曾因對受試者中發現的某些代謝物存有疑慮而拒絕批準這款藥物,其市場獨占7年(ODE)。主要專利包括EP2326643、NZ591615、CN102186848等。
              除了亨廷頓舞蹈癥的應用外,Teva還致力于推動這款藥物在圖雷特氏病(Tourette's disease,I期)、遲發性運動障礙(Tardive dyskinesia,III期)等疾病領域的應用,EvaluatePharma已將這款藥物列為潛在的重磅級藥物。有預測顯示,2021年,Austedo市場可達700M USD。
               
              拓展:關于氘代藥物
              國際上,除了Auspex,專注氘代藥物研究的藥企還有Concert Pharmaceuticals等,Concert先后與葛蘭素史克、爵士制藥、新基等藥企開展合作。國內方面,蘇州澤璟是氘代藥物開發的代表企業,重點開發抗腫瘤藥物等的氘代藥物,包括索拉菲尼、色瑞替尼、艾拉利司、奧貝膽酸等的氘代藥物。相對于其他新藥,氘代藥物風險明較低,而開發速度則可以大大加快。以澤璟生物進展最快的多納非尼(索拉菲尼的氘代藥物)為例,肝細胞癌完成I期臨床后,直接跳過II期進入III期臨床,開發周期大大縮短。

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