专家意见新兴药物

StephenW

专家意见新兴药物

. 2022 年 5 月 5 日。
doi: 10.1080/14728214.2022.2074977。在印刷之前在线。
评估乙型肝炎治疗中药物治疗的发展前景：II期临床试验药物的聚焦
Rex Wan-Hin Hui 1 , Lung Yi Mak 1 2 , Wai-Kay Seto 1 2 , Man-Fung Yuen 1 2
隶属关系
隶属关系

    1
    香港大学医学系。
    2
    香港大学肝脏研究国家重点实验室。

    PMID：35511483 DOI：10.1080/14728214.2022.2074977

抽象的

简介：功能性治愈，定义为持续的 HBsAg 血清学清除，与慢性乙型肝炎 (CHB) 的良好结果相关。虽然核苷（酸）类似物 (NAs) 可有效抑制 HBV 复制，但 NAs 无法以高速率诱导功能性治愈。目前正在开发一系列旨在诱导功能性治愈的新型 HBV 抗病毒药物。

涵盖的领域：本文介绍了已进入 II 期试验的新型乙型肝炎病毒 (HBV) 抗病毒药物。涵盖的病毒导向剂包括进入抑制剂、转录抑制剂、RNA 沉默剂、核心蛋白变构调节剂、非竞争性聚合酶抑制剂和病毒蛋白输出抑制剂。涵盖的免疫调节剂包括先天免疫刺激剂、T 细胞调节剂、治疗性疫苗和单克隆抗体。还将讨论即将到来的发展方向。

专家意见：在新型 HBV 抗病毒药物中，RNA 沉默剂、病毒蛋白输出抑制剂（含聚乙二醇干扰素）和进入抑制剂（含聚乙二醇干扰素）似乎可有效抑制 HBsAg，甚至可能诱导功能性治愈。其他病毒靶向剂对 HBV DNA、HBsAg、HBeAg 和 HBcrAg 有不同的影响。免疫调节剂对 HBsAg 的影响不大，但可能在联合治疗中发挥重要作用。即将进行的试验将回答有关理想剂量、长期药物效果和联合方案疗效的重要问题。

关键词：CPAM；进入抑制剂；功能性治愈；乙肝病毒；乙肝表面抗原；免疫调节剂；小睡；聚合酶抑制剂；核糖核酸干扰。

StephenW

Expert Opin Emerg Drugs

. 2022 May 5.
doi: 10.1080/14728214.2022.2074977. Online ahead of print.
Assessing the developing pharmacotherapeutic landscape in hepatitis B treatment: A spotlight on drugs at phase II clinical trials
Rex Wan-Hin Hui  1 , Lung Yi Mak  1   2 , Wai-Kay Seto  1   2 , Man-Fung Yuen  1   2
Affiliations
Affiliations

    1
    Department of Medicine, The University of Hong Kong, Hong Kong.
    2
    State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong.

    PMID: 35511483 DOI: 10.1080/14728214.2022.2074977

Abstract

Introduction: Functional cure, defined as sustained HBsAg seroclearance, is associated with favorable outcomes in chronic hepatitis B (CHB). While nucleos(t)ide analogues (NAs) are effective in suppressing HBV replication, NAs are unable to induce functional cure at high rates. A range of novel HBV antivirals, aiming to induce functional cure, are currently under development.

Areas covered: This article covered novel hepatitis B virus (HBV) antivirals that have entered phase II trials. Virus-directing agents covered include entry inhibitors, transcription inhibitors, RNA silencers, core protein allosteric modulators, non-competitive polymerase inhibitors, and viral protein export inhibitors. Immunomodulators covered include innate immune stimulators, T-cell modulators, therapeutic vaccines, and monoclonal antibodies. Upcoming developmental directions would also be discussed.

Expert opinion: Among novel HBV antivirals, RNA silencers, viral protein export inhibitors (with pegylated interferon) and entry inhibitors (with pegylated interferon) appear to be effective in suppressing HBsAg and may even induce functional cure. The other virus-targeting agents have variable effects on HBV DNA, HBsAg, HBeAg and HBcrAg. Immunomodulators have modest effects on HBsAg, but may have important roles in combination therapy. Upcoming trials will answer important questions on ideal dosing, long-term drug effects, and efficacy of combination regimens.

Keywords: CpAM; Entry inhibitor; Functional cure; HBV; HBsAg; Immunomodulator; NAPs; Polymerase inhibitor; RNAi.