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Drugs. 2013 Dec;73(18):2093-106. doi: 10.1007/s40265-013-0153-9.
Simeprevir (Sovriad(TM)) is a new direct-acting antiviral drug and a second-generation small-molecule NS3/4A serine protease inhibitor developed by Janssen and Medivir for the oral treatment of adults with genotype 1 and/or genotype 4 chronic hepatitis C virus (HCV) infection (chronic hepatitis C). Simeprevir antiviral activity is achieved by its non-covalent binding to HCV protease, with a fast association and slow dissociation rate. The capsule formulation is approved in Japan and Canada for use in combination with pegylated interferon (peginterferon) and ribavirin for genotype 1 chronic hepatitis C, and has been filed for approval in the US in this indication. In addition, the capsule formulation has been filed for approval in the EU for use in combination with peginterferon and ribavirin for genotype 1 and 4 chronic hepatitis C. Phase III trials of the capsule formulation of simeprevir are underway in several other regions, including China. In the pivotal phase III trials, simeprevir was administered once daily for 12 weeks in combination with peginterferon and ribavirin for 24 or 48 weeks. This article summarizes the milestones in the development of simeprevir leading to this first approval for chronic hepatitis C.
西美瑞韦(Sovriad(TM))是 Janssen 和 Medivir 公司研发的一种新型直接作用抗病毒药物和第二代小分子 NS3/4A 丝氨酸蛋白酶抑制剂,用于治疗基因型 1 和/或基因型 4 慢性丙型肝炎病毒(HCV)感染(慢性丙型肝炎)的成人患者。西美瑞韦的抗病毒活性是通过其与 HCV 蛋白酶的非共价结合来实现的,其具有快速结合和缓慢解离的特性。胶囊制剂已在日本和加拿大获得批准,与聚乙二醇干扰素(peginterferon)和利巴韦林联合用于治疗基因型 1 慢性丙型肝炎,且已在美国针对该适应证提交了上市申请。此外,胶囊制剂已在欧盟提交了用于基因型 1 和 4 慢性丙型肝炎的 peginterferon 和利巴韦林联合治疗的适应证申请。西美瑞韦胶囊制剂的 III 期临床试验正在中国等其他几个地区进行。在关键性 III 期临床试验中,西美瑞韦胶囊与 peginterferon 和利巴韦林联合使用,疗程为 12 周,随后 peginterferon 和利巴韦林继续使用 24 或 48 周。本文总结了西美瑞韦研发历程中的重要里程碑,最终该药获得了慢性丙型肝炎的首个适应证批准。