GlaxoSmithKline (GSK) announced positive topline results from its two pivotal Phase III B-Well 1 and B-Well 2 trials evaluating bepirovirsen, an investigational antisense oligonucleotide targeting chronic hepatitis B (CHB). Both studies met their primary endpoint, demonstrating statistically significant and clinically meaningful functional cure rates when bepirovirsen was combined with standard of care versus standard of care alone.

CHB affects more than 250 million people globally and is an underlying cause in around 56% of all liver cancer cases. Current antiviral therapies often require lifelong treatment and achieve functional cure – defined as sustained loss of hepatitis B surface antigen (HBsAg) and undetectable viral DNA 24 weeks after finite therapy – in only about 1% of patients.

Trial summary

B-Well 1 and B-Well 2 enrolled over 1,800 participants across 29 countries. In both trials, patients receiving bepirovirsen plus standard nucleos(t)ide analogue therapy exhibited significantly higher functional cure rates than those on standard of care alone. The benefit was consistent across primary and ranked secondary endpoints and was particularly pronounced in patients with lower baseline HBsAg levels.

The safety and tolerability profile of bepirovirsen in the B-Well studies was in line with prior data, with no new safety signals emerging. Full trial results will be presented at an upcoming scientific congress and submitted for peer-reviewed publication.

GSK plans to leverage these data to support global regulatory filings beginning in Q1 2026. GSK views bepirovirsen as a potentially transformative new treatment option for people living with CHB, and is a significant part of GSK’s expanding hepatology pipeline aimed at improving liver disease outcomes.

About bepirovirsen

Discovered by California-based biotech Ionis Pharmaceuticals and licensed to GSK in 2019, bepirovirsen is an antisense oligonucleotide (ASO) targeting hepatitis B virus (HBV) mRNA. This mechanism is distinct from the mainstay nucleos(t)ide analogues (NAs) like entecavir and tenofovir, which inhibit viral polymerase, and from interferon-based therapies, which modulate immune responses. Bepirovirsen’s approach aims to reduce all HBV proteins, including HBsAg, potentially enabling functional cure by promoting immune control and HBsAg loss. Phase 2 data for the drug was previously published to Nature Medicine.

Research context

The competitive landscape for chronic hepatitis B (CHB) is shifting rapidly toward mechanism-driven strategies aimed at achieving a functional cure, with development now centred on RNA-targeting therapies, immune modulation and, increasingly, approaches that directly address the persistent viral reservoir.

Among the most advanced competitors to GSK’s antisense oligonucleotide bepirovirsen are RNA interference (RNAi) therapies, which target hepatitis B virus (HBV) transcripts through a complementary but mechanistically distinct pathway. While antisense drugs recruit RNase H to degrade viral RNA, RNAi agents act via the RISC complex to silence gene expression and are increasingly being positioned as part of combination regimens.

A leading programme in this class is Vir Biotechnology’s elebsiran (VIR-2218), which is being evaluated in multiple Phase 2 and Phase 3 studies, often alongside other investigational agents such as VIR-3434, a monoclonal antibody targeting hepatitis B surface antigen, and pegylated interferon alfa-2a (PEG-IFN-α). These combinations reflect a growing consensus that durable functional cure will require multi-mechanism therapy rather than monotherapy.

Beyond RNA-targeting approaches, the field is now moving into a new phase with the emergence of reservoir-directed strategies. Gene-editing programmes designed to eliminate or inactivate cccDNA and integrated HBV DNA have begun to enter early clinical development, representing the first concerted attempt to address the root biological basis of viral persistence. In parallel, epigenetic silencing technologies are being developed to durably suppress transcription from cccDNA, offering an alternative route to long-term antigen reduction without permanent genome modification.

Together, these next-generation modalities — RNA-targeting agents, combination immunotherapies, gene editing and epigenetic control — signal a transition in CHB drug development from incremental viral suppression toward true disease-modifying and potentially curative strategies.