The pharmaceutical industry is witnessing significant advancement in the development of therapies for chronic hepatitis B virus (HBV) infection, with over 50 companies actively working on 55+ pipeline drugs aimed at achieving functional cures for patients.
According to DelveInsight's "Chronic Hepatitis B Virus Pipeline Insight 2025" report, the treatment landscape for this persistent viral infection is evolving rapidly, with therapies spanning various development stages from preclinical to Phase III trials.
Key Pipeline Developments
Vir Biotechnology announced in April 2025 the initiation of a phase 1b/2 platform study to evaluate investigational candidates and their combinations for treating adults with chronic HBV infection. This platform approach aims to identify optimal therapeutic combinations that could potentially lead to functional cures.
Simultaneously, GlaxoSmithKline (GSK) is pursuing a sequential treatment strategy, assessing the safety, efficacy, and immune response following treatment with their antisense oligonucleotide compound (GSK3228836) and CHB-TI (GSK3528869A) in patients stabilized on nucleoside/nucleotide analog (NA) therapy. The study will evaluate whether sequential therapy provides added value over GSK3228836 monotherapy and will assess different treatment durations (12 or 24 weeks) of GSK3228836 before initiating GSK3528869A treatment.
Advanced-Stage Candidates
Among the late-stage candidates, Pradefovir from Ligand Pharmaceuticals stands out in Phase III development. This oral liver-targeting prodrug of adefovir utilizes Ligand's HepDirect technology to inhibit HBV DNA polymerase/reverse transcriptase, potentially offering improved efficacy with reduced systemic toxicity compared to current treatments.
In the mid-stage pipeline, RG6346 (Dicerna Pharmaceuticals, in collaboration with Roche) represents an innovative approach using RNA interference (RNAi) technology. This GalXC™ RNAi therapeutic candidate selectively targets genes involved in HBV messenger RNA creation and viral entry into liver cells. Preclinical data have demonstrated remarkable efficacy, with greater than 99.9% reduction in circulating hepatitis B surface antigen (HBsAg) in mouse models of HBV infection.
Diverse Therapeutic Approaches
The pipeline encompasses diverse therapeutic modalities, including:
- Monoclonal antibodies
- Peptides
- Polymers
- Small molecules
- Gene therapies
These therapies are being developed for various routes of administration, including oral, parenteral, intravenous, subcutaneous, and topical applications, providing multiple options to address patient needs and treatment preferences.
Leading Companies in HBV Research
The competitive landscape features numerous pharmaceutical companies investing in chronic HBV research, including Vedanta Biosciences, Gilead Sciences, Dong-A ST Co, Assembly Biosciences, Arbutus Biopharma, Vir Biotechnology, Antios Therapeutics, Ascletis Pharmaceuticals, GlaxoSmithKline, Janssen Sciences, Brii Biosciences, Enanta Pharmaceuticals, and many others.
Notable pipeline therapies include Peginterferon Alfacon, Daplusiran/Tomligisiran, Bepirovirsen, Tenofovir disoproxil fumarate (TDF), VIR-2218, and PEG-IFNα, among others.
Early-Stage Innovations
The early-stage pipeline also shows promise, with candidates like VIR-3434 from Vir Biotechnology in Phase I development. Additionally, preclinical candidates such as SBT8230 from Silverback Therapeutics are advancing through development, potentially offering new mechanisms of action to combat chronic HBV infection.
Shifting Treatment Paradigm
Current standard treatments for chronic HBV typically provide long-term viral suppression rather than elimination. However, the emerging pipeline therapies aim to shift this paradigm toward achieving functional cures, where patients maintain sustained virologic suppression without ongoing therapy.
Dr. James Chen, a hepatologist not affiliated with any of the companies mentioned (fictional quote for illustration), notes: "The diversity of approaches in the current HBV pipeline is unprecedented. From novel direct-acting antivirals to immunomodulatory agents and gene silencing technologies, we're attacking the virus from multiple angles simultaneously. This gives us real hope for achieving functional cures in the coming years."
Market Implications
The robust pipeline reflects growing recognition of the significant unmet medical need in chronic HBV treatment. With approximately 296 million people living with chronic HBV worldwide according to WHO estimates, successful development of functional cures would represent a major advancement in global public health.
Industry analysts suggest that the first therapies to achieve reliable functional cures could capture substantial market share, potentially transforming the treatment landscape for this persistent viral infection.
Future Outlook
As these pipeline candidates progress through clinical development, combination approaches are likely to emerge as the most promising strategy for achieving functional cures. By targeting multiple aspects of the HBV lifecycle simultaneously, these combination regimens may overcome the virus's ability to persist in infected hepatocytes.
The next few years will be critical in determining which of these approaches demonstrates the optimal balance of efficacy, safety, and convenience for patients with chronic HBV infection.
