Bepirovirsen Achieves Phase 3 Functional Cure Rates in Chronic Hepatitis B, Supporting Potential Shift Beyond Lifelong Therapy

New Phase 3 data suggest that bepirovirsen may move chronic hepatitis B (CHB) treatment closer to a long-sought goal: functional cure. GSK announced that pooled results from its pivotal B-Well 1 and B-Well 2 studies demonstrated statistically significant functional cure rates in patients receiving the investigational therapy, with findings simultaneously published in The New England Journal of Medicine and presented at the 2026 European Association for the Study of the Liver Congress.¹˒²

Current antiviral therapies typically suppress viral replication but rarely achieve functional cure, often requiring lifelong treatment.²˒⁴ The new data suggest that a finite treatment course with bepirovirsen could offer a substantially different approach to disease management.

What did the B-Well trials show?

The global Phase 3 B-Well program enrolled 1,834 participants across 29 countries and evaluated bepirovirsen in adults with chronic hepatitis B who were receiving nucleos(t)ide analogue therapy. The primary endpoint measured functional cure, defined as sustained loss of hepatitis B surface antigen (HBsAg) and undetectable hepatitis B virus (HBV) DNA for at least six months after stopping treatment.¹˒²

Pooled analyses demonstrated a 19% functional cure rate among patients with baseline HBsAg levels of 3,000 IU/mL or less, compared with 0% in the placebo group. Among patients with HBsAg levels of 1,000 IU/mL or less, functional cure rates increased to 26%, also compared with 0% for placebo.¹˒² Both endpoints achieved statistical significance.

Investigators also reported that 49% of patients receiving bepirovirsen achieved HBsAg levels of 100 IU/mL or less one year after treatment completion in an exploratory analysis, a marker associated with improved immune control and favorable long-term outcomes.¹˒²

How does bepirovirsen work?

Bepirovirsen is an antisense oligonucleotide licensed from Ionis Pharmaceuticals. The therapy is designed to bind HBV RNA transcripts, reducing production of viral proteins and suppressing expression of hepatitis B surface antigen. This reduction may allow the patient's immune system to regain control over the infection and sustain viral suppression after treatment discontinuation.²

Researchers believe this mechanism differentiates bepirovirsen from currently available antiviral therapies, which primarily inhibit viral replication but generally do not eliminate HBsAg production.²

Why could these results have a significant global health impact?

Chronic hepatitis B remains one of the world's most prevalent infectious diseases, affecting an estimated 250 to 300 million people globally and contributing to hundreds of thousands of deaths annually from cirrhosis, liver failure, and liver cancer.³ Despite the availability of antiviral therapies that can effectively suppress viral replication, most patients require lifelong treatment and only a small fraction achieve functional cure.²˒⁴

Against that backdrop, the Phase 3 B-Well findings have attracted considerable attention within the hepatology community. In pooled analyses, bepirovirsen achieved functional cure rates that substantially exceed the rates typically observed with current standard-of-care therapies.¹˒²

While chronic hepatitis B may not command the same commercial attention as many oncology indications, the disease burden remains enormous. If approved, bepirovirsen could represent one of the first therapies capable of delivering meaningful functional cure rates through a finite treatment course, potentially altering treatment expectations for millions of patients worldwide.¹˒²˒³

What could the findings mean for clinical practice?

The results arrive as treatment guidelines increasingly recognize functional cure as an important objective in chronic hepatitis B management. If approved, bepirovirsen could become one of the first therapies specifically designed to help patients discontinue treatment while maintaining long-term viral control.²˒⁴

GSK has submitted regulatory applications in the United States, Europe, Japan, and China. The therapy has received several expedited review designations, including Breakthrough Therapy and Fast Track status from the US Food and Drug Administration.² The company expects initial regulatory decisions later in 2026.

For clinicians and patients, the B-Well findings represent one of the strongest demonstrations to date that a finite-course therapy may be capable of achieving meaningful functional cure rates in chronic hepatitis B, potentially reshaping treatment expectations for a disease that has historically required lifelong management.¹˒²

References

1. Hou J. L., Lim S. G., Buti M., et al. (2026 May 28). Phase 3 Results of Bepirovirsen Treatment for Chronic Hepatitis B Virus Infection. New England Journal of Medicine. https://www.nejm.org/doi/full/10.1056/NEJMoa2515131
2. Bepirovirsen achieves unprecedented functional cure rates with potential to redefine treatment for chronic hepatitis B. (2026 May 28). GSK. https://www.gsk.com/en-gb/media/press-releases/bepirovirsen-achieves-unprecedented-functional-cure-rates-with-potential-to-redefine-treatment-for-chronic-hepatitis-b/ 
3. Global Hepatitis Report 2026. World Health Organization. https://www.who.int/teams/global-hiv-hepatitis-and-stis-programmes/hepatitis/reports/global-hepatitis-report-2026 
4. Clinical Practice Guidelines on the Management of Hepatitis B Virus Infection. (2025 Aug).European Association for the Study of the Liver. Journal of Hepatology. https://www.journal-of-hepatology.eu/article/S0168-8278(25)00174-6/fulltext