治疗慢性乙型肝炎新药研发的研究进展

刘义思; 陈新月

doi:10.3969/j.issn.1001-5256.2022.06.035

治疗慢性乙型肝炎新药研发的研究进展

DOI: 10.3969/j.issn.1001-5256.2022.06.035

刘义思,
陈新月^, ,

首都医科大学附属北京佑安医院肝病中心一科，北京 100069

基金项目:

北京市医院管理中心重点医学专业发展计划(扬帆计划)资助 (ZYLX202125);

首都卫生发展科研专项项目 (首发2020-1-2181)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：刘义思负责文献检索和撰写；陈新月负责拟定写作思路，终审定稿。

详细信息

通信作者:
陈新月，chenxydoc@163.com

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出版历程
- 收稿日期: 2021-10-29
- 录用日期: 2021-12-20
- 出版日期: 2022-06-20

Advances in the research and development of new drugs for chronic hepatitis B

Yisi LIU,
Xinyue CHEN^{,
,}

First Department of Liver Disease Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China

More Information

Corresponding author: CHEN Xinyue, chenxydoc@163.com(ORCID: 0000-0003-3212-2398)

摘要

摘要: 当前针对慢性乙型肝炎的抗病毒治疗临床治愈率低，并且难以清除cccDNA。随着医药水平的进步，越来越多的新药正处于研发阶段。重点阐述临床试验数据较详尽代表性药物的研发情况。近些年来小干扰RNA、核心蛋白变构调节剂等新药进展较快。从临床试验结果来看，新药进入临床使用仍需一定的时间，并且多药联合方案可能会成为今后的治疗趋势。
- 乙型肝炎, 慢性 /
- 药物发现 /
- 临床试验
Abstract: At present, antiviral therapy for chronic hepatitis B (CHB) has a low clinical cure rate and hardly remove cccDNA. With the progress of medical science, more and more new drugs are in the stage of research and development. This article focuses on the research and development of representative drugs with relatively detailed clinical trial data. Rapid progress has been made in the new drugs such as small-interfering RNA and core protein allosteric modulators in recent years. The results of clinical trials show that it still takes some time for new drugs to enter clinical use, and multi-drug combination therapy may become the trend of treatment in the future.
- Hepatitis B, Chronic /
- Drug Discovery /
- Clinical Trial

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图 1 HBV生命周期及相关药物靶点

Figure 1. HBV life cycle and drug targets in development

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表 1 治疗CHB的在研药物

Table 1. The drug for chronic hepatitis B in development

药物名称	类别	生产公司	研发阶段
Hepcludex (Bulevirtide)	进入抑制剂	Hepatera, Russia with MYR GmbH, Germany	Ⅱ期
HH-003	进入抑制剂	Huahui Health, China	Ⅱ期
EBT-107	CRISPR/Cas9	Excision Biotherapeutic, USA	临床前
JNJ-3989 (ARO-HBV)	siRNA	Arrowhead pharma, USA with Janssen	Ⅱb期
ALN-HBV02 (VIR-2218)	siRNA	Alnylam and VirBiotech, USA	Ⅱ期
DCR-HBVS (RG6346)	siRNA	Roche with Dicerna, USA	Ⅱ期
AB-729 (GalNAc-RNAi)	siRNA	Arbutus Biopharma, USA	Ⅰb期
ALG-125775	siRNA	Aligos Therapeutics, USA	Ⅰ期
GSK3228836 (IONIS-HBVRx)	ASO	Ionis Parma, USA with GSK	Ⅱ期
ALG-020572 (formerly ALG-ASO)	ASO	Aligos Therapeutics, USA	Ⅰ期
GLS4 (Morphothiadin)	CpAM	HEC Pharma, China	Ⅱ期
ABI-H0731 (Vebicorvir)	CpAM	Assembly Biosciences, USA with BeiGene, China	Ⅱ期
JNJ-6379	CpAM	Janssen, Ireland	Ⅱ期
RG7907	CpAM	Roche, Switzerland	Ⅰ期
GST-HG141	CpAM	Cosunter pharmaceutical co., LTD, Fujian, China	Ⅰb期
REP 2139	HBsAg抑制剂	Replicor, Canada	Ⅱ期
REP 2165	HBsAg抑制剂	Replicor, Canada	Ⅱ期
GST-HG131	HBsAg抑制剂	Cosunter pharmaceutical co., LTD, Fujian, China	Ⅰ期
GS-9688 (Selgantolimod)	TLR-8激动剂	Gilead Sicence, USA	Ⅱ期
RG7854	TLR-7激动剂	Roche, Switzerland	Ⅱ期
ASC-22 (KN-035)	PD-L1抑制剂	Ascletis Pharma, China	Ⅱb期
GS-4224	PD-L1抑制剂	Gilead Sciences, USA	Ⅰ期
NASVAC	治疗性疫苗	CIGB, Cuba	Ⅲ期
CVI-HBV-002	治疗性疫苗	CHA Vaccine Institute, Korea	Ⅱb期
GS-4774	治疗性疫苗	GobeImmune with Gilead, USA	Ⅱ期
HepTcell	治疗性疫苗	Altimmune, USA	Ⅱ期
TG1050	治疗性疫苗	Transgene, France with Tasly, China	Ⅱ期

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