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正在研发的丙型肝炎药物。

Drugs in development for hepatitis C.

作者信息

Stauber Rudolf E, Kessler Harald H

机构信息

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.

出版信息

Drugs. 2008;68(10):1347-59. doi: 10.2165/00003495-200868100-00002.

Abstract

Currently available anti-hepatitis C virus (HCV) therapy is effective in only half of infected patients and is limited by adverse effects that often necessitate discontinuation. Therefore, new treatments are being developed, including optimization of current standard treatment with peginterferon plus ribavirin, specifically targeted antiviral therapy for HCV, novel immunomodulatory agents and treatments aimed at reducing fibrosis. This review focuses on novel anti-HCV drugs that are currently in an advanced stage of clinical development. Albinterferon-alpha-2b, a fusion molecule of albumin and interferon-alpha-2b, has a longer half-life than peginterferon, which enables a bi-weekly administration interval. Preliminary data indicate similar response rates for albinterferon-alpha-2b plus ribavirin compared with peginterferon-alpha-2b plus ribavirin, but possible benefits with respect to quality of life. Telaprevir, a NS3/4 protease inhibitor, demonstrated a rapid and profound antiviral effect in phase I trials that was synergistic with that of peginterferon-alpha-2a. Recently completed phase II trials on triple combination treatment with telaprevir, peginterferon-alpha-2a and ribavirin given for 12-24 weeks reported sustained virological response in up to 68% of patients with treatment-naive HCV genotype 1 infection.

摘要

目前可用的抗丙型肝炎病毒(HCV)疗法仅对一半的感染患者有效,且受不良反应限制,这些不良反应常使治疗不得不中断。因此,正在研发新的治疗方法,包括优化聚乙二醇干扰素联合利巴韦林的现行标准治疗、针对HCV的特异性靶向抗病毒疗法、新型免疫调节剂以及旨在减轻纤维化的治疗方法。本综述聚焦于目前处于临床开发后期的新型抗HCV药物。α-2b白蛋白干扰素是白蛋白与α-2b干扰素的融合分子,其半衰期比聚乙二醇干扰素长,这使得给药间隔可为两周一次。初步数据表明,与α-2b聚乙二醇干扰素联合利巴韦林相比,α-2b白蛋白干扰素联合利巴韦林的应答率相似,但在生活质量方面可能具有优势。替拉瑞韦是一种NS3/4蛋白酶抑制剂,在I期试验中显示出快速且显著的抗病毒作用,与α-2a聚乙二醇干扰素具有协同作用。最近完成的关于替拉瑞韦、α-2a聚乙二醇干扰素和利巴韦林三联联合治疗12 - 24周的II期试验报告称,在初治的HCV基因1型感染患者中,高达68%的患者实现了持续病毒学应答。

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