Bepirovirsen Achieves Functional Cure in Chronic Hepatitis B: NEJM | May 2026
Clinical knowledge base written and curated by GastroAGI Team from primary medical literatureLast updated May 1, 2026
- Bepirovirsen is an antisense oligonucleotide that targets HBV transcripts, aiming to reduce viral proteins and achieve a functional cure rather than lifelong viral suppression.
- In two large Phase 3 trials (B-Well 1 and B-Well 2), approximately 20% of treated patients achieved functional cure, compared with 0% in the placebo group.
- Functional cure was defined as sustained HBV DNA suppression below the limit of quantification together with HBsAg loss, maintained for at least 24 weeks after treatment.
- The results were highly consistent across both studies, with cure rates of 20% in B-Well 1 and 19% in B-Well 2, providing strong validation of the treatment effect.
- All patients were receiving stable nucleos(t)ide analogue therapy at study entry, and antiviral therapy was subsequently discontinued, demonstrating the potential for finite-duration treatment.
- The study provides some of the strongest evidence to date that chronic HBV infection can be functionally cured without indefinite antiviral therapy.
- Adverse events were more common with bepirovirsen than placebo. The most frequent significant adverse event was ALT elevation, which may reflect immune-mediated clearance of infected hepatocytes.
- Serious adverse events were relatively uncommon, occurring in 7% of bepirovirsen-treated patients compared with 4% of placebo-treated patients.
- Although highly encouraging, approximately 80% of patients did not achieve functional cure, indicating that further improvements are still needed.
- Bepirovirsen is likely to become an important component of future combination cure strategies, potentially alongside siRNA therapies, therapeutic vaccines, and immune modulators.
- The trial represents a major milestone in HBV therapeutics and moves the field closer to the long-sought goal of a practical and scalable cure for chronic hepatitis B.
Bottom Line: Bepirovirsen is the first antisense oligonucleotide to demonstrate Phase 3 functional cure rates of approximately 20% in chronic hepatitis B, marking one of the most important advances in HBV treatment in the past decade.
