Hepatitis B cure: From discovery to regulatory approval.
Hepatitis B cure: From discovery to regulatory approval.
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DOI：
10.1002/hep.29323
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发表时间：
2017-10
期刊：
影响因子：
--
通讯作者：
Ghany MG
中科院分区：
文献类型：
--
作者：
Lok AS;Zoulim F;Dusheiko G;Ghany MG
目前接受慢性B型肝炎治疗的大多数人需要长期或终身治疗。新的B型肝炎病毒进入、复制、装配或分泌的抑制剂以及免疫调节疗法正在开发中。引入这些新型化合物治疗慢性B型肝炎需要对这些治疗的有效性和安全性进行标准化评估，并定义新的或额外的终点，以告知临床试验。为了推动该领域向前发展，并加快从发现到监管批准的进程，2016年9月与主要利益相关者举行了一次研讨会，就治疗终点达成共识，以指导旨在治愈B型肝炎的临床试验的设计。达成的共识是，完全的灭菌治疗，即从宿主中根除病毒不太可能是可行的。相反，一个功能性治愈的特点是持续的HBsAg丢失，有或没有抗-HBs血清转换，这与改善的临床结果，在更高比例的患者比目前实现现有的治疗是一个可行的目标。开发新的生物标志物的标准化检测方法，以更好地定义HBV治愈，应与开发新的抗病毒和免疫调节治疗方法同时进行，以便新治疗方法的批准可以与用于测量疗效或预测反应的新诊断检测方法的批准相关联。抗病毒和免疫调节治疗的组合可能需要实现功能性HBV治愈。在进行联合治疗之前，应进行有限的概念验证单药治疗研究，以评估安全性和抗病毒活性。鉴于目前批准的核苷（酸）类似物的优异安全性，任何新的治愈性疗法的安全性将是至关重要的。
The majority of persons currently treated for chronic hepatitis B require long-term or lifelong therapy. New inhibitors of hepatitis B virus entry, replication, assembly or secretion, and immune-modulatory therapies are in development. The introduction of these novel compounds for chronic hepatitis B necessitates a standardized appraisal of the efficacy and safety of these treatments, and definitions of new or additional endpoints to inform clinical trials. To move the field forward, and to expedite the pathway from discovery to regulatory approval, a workshop with key stake holders was held in September 2016 to develop a consensus on treatment endpoints to guide the design of clinical trials aimed at hepatitis B cure. The consensus reached was that a complete sterilizing cure i.e. viral eradication from the host is unlikely to be feasible. Instead, a functional cure characterized by sustained loss of HBsAg with or without anti-HBs seroconversion, which is associated with improved clinical outcomes, in a higher proportion of patients than is currently achieved with existing treatments is a feasible goal. Development of standardized assays for novel biomarkers towards better defining HBV cure should occur in parallel with development of novel antiviral and immune modulatory therapies such that approval of new treatments can be linked to the approval of new diagnostic assays used to measure efficacy or to predict response. Combination of antiviral and immune modulatory therapies will likely be needed to achieve functional HBV cure. Limited proof-of-concept monotherapy studies to evaluate safety and antiviral activity should be conducted prior to proceeding to combination therapies. The safety of any new curative therapies will be paramount given the excellent safety of currently approved nucleos(t)ide analogues.
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影响因子：
120.7
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