乙型肝炎功能性治愈新药临床价值评价标准的探讨

左书凝; 钟钰婷; 赵建中

doi:10.12449/JCH260806

乙型肝炎功能性治愈新药临床价值评价标准的探讨

DOI: 10.12449/JCH260806

国家药品监督管理局药品审评中心，北京 100163

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：左书凝负责文献调研，资料分析，撰写论文；钟钰婷参与文献调研，修改论文；赵建中负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
赵建中， zhaojzh@cde.org.cn （ORCID： 0009-0002-5606-1315）

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出版历程
- 收稿日期: 2026-07-10
- 录用日期: 2026-07-29
- 出版日期: 2026-08-25

Perspectives on assessing the clinical value of novel drugs for achieving functional cure of chronic hepatitis B

Center for Drug Evaluation，National Medical Products Administration，Beijing 100163，China

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Corresponding author: Zhao Jianzhong， zhaojzh@cde.org.cn （ORCID： 0009-0002-5606-1315）

摘要

摘要: 我国乙型肝炎疾病负担较重，在现行慢性乙型肝炎临床诊疗方案中，对满足治疗指征的患者，临床治疗以争取功能性治愈（临床治愈）为核心目标。针对功能性治愈目标，国内外药品监督管理机构相继发布技术标准，指导创新药物临床试验的整体设计与科学评价。但随着该领域科学研究、临床实践和新药研发的快速发展，出现了一些新的挑战，特别是新药临床价值评价问题。本文综述国内外乙型肝炎功能性治愈新药的临床研发现状，分析现有临床试验数据特点，重点探讨乙型肝炎功能性治愈关键性临床试验的目标人群［基线乙型肝炎病毒表面抗原（HBsAg）水平］、HBsAg清除的应答、停药后HBsAg血清学逆转情况以及有临床价值的功能性治愈应答率目标值等，为进一步完善技术标准提供参考。
- 乙型肝炎，慢性 /
- 功能性治愈 /
- 药物，临床试用
Abstract: China bears a substantial disease burden of chronic hepatitis B （CHB）. Under current clinical management regimens for CHB， achieving functional cure （also termed clinical cure） is the core goal for the treatment of patients meeting treatment indications. To achieve the goal of functional cure， drug regulatory authorities in China and globally have successively issued technical criteria to provide guidance for the overall design and scientific evaluation of clinical trials for innovative drugs. However， the rapid development in scientific research， clinical practice， and new drug research and development in this field has brought new challenges， especially those concerning the assessment of the clinical value of investigational drugs. This article reviews the current status of clinical research and development of new drugs for achieving the functional cure of CHB worldwide， analyzes the characteristics of available clinical trial data， and focuses on key aspects of pivotal clinical trials for CHB functional cure drugs， including target populations （baseline HBsAg level）， HBsAg seroclearance response， HBsAg seroreversion after drug withdrawal， and clinically meaningful target threshold of functional cure response rate， in order to provide a reference for further refinement of related technical criteria.
- Hepatitis B， Chronic /
- Functional Cure /
- Drugs， Investigational

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表 1 乙型肝炎功能性治愈新药在不同HBsAg水平患者中的应答率

Table 1. Response rates of functional-cure-targeted novel drugs in CHB patients of different HBsAg levels

在研新药	研究代码	基线HBsAg 水平	总体人群应答	低HBsAg亚组应答	高HBsAg亚组应答
Bepirovirsen （GSK3228836）	B-Clear（Ⅱ期）^［10］	>100 IU/mL	9% （EOT后24周）	≤1 000 IU/mL：22% （EOT后24周）	>1 000 IU/mL：6% （EOT后24周）
Bepirovirsen （GSK3228836）	B-Well 1（Ⅲ期）^［11］	100～3 000 IU/mL	20%（停用所有治疗药物后24周）	≤1 000 IU/mL：25% （停用所有治疗药物后 24周）	>1 000 IU/mL：10%（停用所有治疗药物后24周）
Bepirovirsen （GSK3228836）	B-Well 2（Ⅲ期）^［11］	100～3 000 IU/mL	19%（停用所有治疗药物后24周）	≤1 000 IU/mL：28% （停用所有治疗药物后 24周）	>1 000 IU/mL：5%（停用所有治疗药物后24周）
AHB-137	AB-10-8002 （Ⅱ期）^［12］	100～3 000 IU/mL	19%（停用所有治疗药物后24周）	≤1 000 IU/mL：29% （停用所有治疗药物后 24周）	>1 000 IU/mL：0%（停用所有治疗药物后24周）
BW-20507	BW‑20507‑CHB‑001 （Ⅰ/Ⅱ期）^［13］	100～3 000 IU/mL	16.1% （EOT后24周）	<1 000 IU/mL：56% （EOT后24周）	>1 000 IU/mL：0% （EOT后24周）
Elebsiran（BRII-835/ VIR-2218）联合 PEG-IFN-α	ENSURE（Ⅱ期）^［14］	100～3 000 IU/mL	33%、21% （EOT后24周）	<1 000 IU/mL：所有应答病例均在此亚组（EOT后24周）	>1 000 IU/mL：0% （EOT后24周）
注：HBsAg，乙型肝炎病毒表面抗原；EOT，治疗结束；PEG-IFN-α，聚乙二醇干扰素α。

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表 2 乙型肝炎功能性治愈新药在基线HBsAg>100 IU/mL患者中各时间点的应答率

Table 2. Response rates at different time-points of novel drugs for functional cure in CHB patients with baseline HBsAg>100 IU/mL

在研新药	研究代码	EOT时间点应答率	新药停药后24周应答率	所有治疗药物停药后24 周应答率
Bepirovirsen	B-Clear（Ⅱ期）^［10］	26%	9%
Bepirovirsen	B-Well 1（Ⅲ期）^［11］	54%（HBsAg清除）	29%（HBsAg清除）	20%（HBsAg和HBV DNA 持续消失）
Bepirovirsen	B-Well 2（Ⅲ期）^［11］	52%（HBsAg清除）	26%（HBsAg清除）	19%（HBsAg和HBV DNA 持续消失）
Bepirovirsen序贯PEG- IFN-α-2a	B-Together （Ⅲ期）^［17］	17%～22%	9%～15%
AHB-137	AB-10-8002 （Ⅱ期）^［12］	63%	22%	19%
AHB-137	AB-10-8003 （Ⅱ期）^［18］	75%	31%
Elebsiran（BRII-835/VIR- 2218）联合PEG-IFN-α	ENSURE （Ⅱ期）^{［14，19］}	33%、26%； 42%（BRII-179经治）	33%、21%； 29%（BRII-179经治）	17%、11%； 26%（BRII-179经治）
HT-101联合HT-102	HT‑CHB‑001^［20］	63%、80%、90%^1）	13%、30%、50%（所有治疗药物停药后24周）
Xalnesiran（RG6346）	Piranga^［21］	单药：7%；联合Ruzotolimod（TLR7激动剂）： 18%；联合PEG-IFN-α-2a：30% （HBsAg清除）	单药：7%；联合Ruzotolimod（TLR7 激动剂）：12%；联合PEG-IFN-α-2a：23% （HBsAg清除）
注：1）该组数据为HT-102 300 mg与不同剂量的HT-101联合用药的应答率，其中63%、80%分别为HT-101 100 mg和200 mg治疗24周的应答率，90%为HT-101 400 mg治疗20周的应答率。HBsAg，乙型肝炎病毒表面抗原；EOT，治疗结束；PEG-IFN-α，聚乙二醇干扰素α；PEG-IFN-α-2a，聚乙二醇干扰素α-2a；TLR7，Toll样受体7。

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