{"title":"Emerging Trends and Future Directions in the Development of Anti-hepatitis B Therapies: A Horizon Scanning Review.","authors":"Kaijie Yao, Hao Feng, Ying Chen, Yun Bao, Mengxia Yan, Wen Li, Bin Wu","doi":"10.1007/s40261-025-01477-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objectives: </strong>Chronic hepatitis B virus infection remains a Major global public health challenge, affecting over 254 million individuals and causing substantial mortality owing to the limited curative potential of current therapies. This horizon scanning review aims to comprehensively analyze emerging trends and future directions in novel anti-hepatitis B virus therapeutic development, evaluating their progress and potential to achieve functional or complete cures.</p><p><strong>Methods: </strong>We conducted a systematic horizon scanning review from January 2020 to June 2025, searching databases (PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure [CNKI], and WanFang), clinical trial registries (ClinicalTrials.gov, EU Clinical Trials Register, World Health Organization International Clinical Trials Registry, Chinese Clinical Trial Registry, and chinadrugtrials.org), hepatology conference abstracts (American Association for the Study of Liver Diseases, European Association for the Study of the Liver), and pharmaceutical company websites. Inclusion criteria focused on studies detailing novel anti-hepatitis B virus treatments, with data extracted on category, target, clinical phase, and discontinuation reasons.</p><p><strong>Results: </strong>Our analysis identified 161 unique anti-hepatitis B virus treatments: 75 in clinical trials, 34 in preclinical development, and 52 discontinued post-clinical trials because of safety or insufficient efficacy. The pipeline reveals a diversification of targets, with capsid assembly modulators, therapeutic vaccines, and monoclonal antibodies being most prevalent. Three therapies representing novel mechanisms have reached phase III-bepirovirsen (an antisense oligonucleotide), canocapavir (a capsid assembly modulator), and εPA-44 (a therapeutic vaccine), illustrating diversification of late-stage pipelines; however, 6-month off-treatment endpoints should be interpreted cautiously across modalities until durability is established.</p><p><strong>Conclusions: </strong>The robust and diverse pipeline of novel anti-hepatitis B virus treatments offers promise for improving functional cure rates, but definitive conclusions await longer off-treatment follow-up and durability data. Continued research, rational combination strategies, and global collaboration are crucial to overcome challenges and ensure equitable access to these transformative therapies worldwide.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"681-700"},"PeriodicalIF":2.7000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Drug Investigation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40261-025-01477-0","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/9/17 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Background and objectives: Chronic hepatitis B virus infection remains a Major global public health challenge, affecting over 254 million individuals and causing substantial mortality owing to the limited curative potential of current therapies. This horizon scanning review aims to comprehensively analyze emerging trends and future directions in novel anti-hepatitis B virus therapeutic development, evaluating their progress and potential to achieve functional or complete cures.
Methods: We conducted a systematic horizon scanning review from January 2020 to June 2025, searching databases (PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure [CNKI], and WanFang), clinical trial registries (ClinicalTrials.gov, EU Clinical Trials Register, World Health Organization International Clinical Trials Registry, Chinese Clinical Trial Registry, and chinadrugtrials.org), hepatology conference abstracts (American Association for the Study of Liver Diseases, European Association for the Study of the Liver), and pharmaceutical company websites. Inclusion criteria focused on studies detailing novel anti-hepatitis B virus treatments, with data extracted on category, target, clinical phase, and discontinuation reasons.
Results: Our analysis identified 161 unique anti-hepatitis B virus treatments: 75 in clinical trials, 34 in preclinical development, and 52 discontinued post-clinical trials because of safety or insufficient efficacy. The pipeline reveals a diversification of targets, with capsid assembly modulators, therapeutic vaccines, and monoclonal antibodies being most prevalent. Three therapies representing novel mechanisms have reached phase III-bepirovirsen (an antisense oligonucleotide), canocapavir (a capsid assembly modulator), and εPA-44 (a therapeutic vaccine), illustrating diversification of late-stage pipelines; however, 6-month off-treatment endpoints should be interpreted cautiously across modalities until durability is established.
Conclusions: The robust and diverse pipeline of novel anti-hepatitis B virus treatments offers promise for improving functional cure rates, but definitive conclusions await longer off-treatment follow-up and durability data. Continued research, rational combination strategies, and global collaboration are crucial to overcome challenges and ensure equitable access to these transformative therapies worldwide.
期刊介绍：
Clinical Drug Investigation provides rapid publication of original research covering all phases of clinical drug development and therapeutic use of drugs. The Journal includes:
-Clinical trials, outcomes research, clinical pharmacoeconomic studies and pharmacoepidemiology studies with a strong link to optimum prescribing practice for a drug or group of drugs.
-Clinical pharmacodynamic and clinical pharmacokinetic studies with a strong link to clinical practice.
-Pharmacodynamic and pharmacokinetic studies in healthy volunteers in which significant implications for clinical prescribing are discussed.
-Studies focusing on the application of drug delivery technology in healthcare.
-Short communications and case study reports that meet the above criteria will also be considered.
Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Clinical Drug Investigation may be accompanied by plain language summaries to assist readers who have some knowledge, but non in-depth expertise in, the area to understand important medical advances.
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