GSK's Bepirovirsen Achieves 19% Functional Cure Rate in Phase III Hepatitis B Trials
GSK's Phase III B-Well trials show bepirovirsen achieved 19% functional cure in chronic hepatitis B, rising to 26% in patients with lower viral activity, versus 0% for placebo. Regulatory decisions are expected in Q3 2026.
GSK plc announced positive Phase III trial results for bepirovirsen, an investigational antisense oligonucleotide for the treatment of chronic hepatitis B (CHB). Pooled data from the Phase III B-Well 1 and B-Well 2 trials showed that 19% of patients receiving bepirovirsen achieved a functional cure, compared with 0% in the placebo group.
Among patients with lower baseline viral activity, defined as hepatitis B surface antigen (HBsAg) levels of 1,000 IU/mL or less, the functional cure rate increased to 26%, also versus 0% for placebo. This subgroup represents approximately 45% of diagnosed CHB cases globally. The results were simultaneously published in the New England Journal of Medicine and presented at the European Association for the Study of the Liver (EASL) congress.
Functional cure occurs when hepatitis B virus DNA and HBsAg are undetectable in the blood for at least six months after stopping all treatment, indicating the disease is controlled by the immune system without medication. A loss in HBsAg is associated with an 89% reduction in risk of liver cancer and a 62% reduction in risk of all-cause mortality.
In an exploratory analysis, 49% of bepirovirsen recipients achieved a quantitative hepatitis B surface antigen level of ≤100 IU/mL one year after the end of treatment. Additionally, 23% of all bepirovirsen-treated patients achieved sustained viral suppression (HBV DNA below the lower limit of quantification) at week 72 after stopping therapy, compared with none in the placebo group. Among patients with baseline HBsAg ≤1000 IU/mL, the sustained viral suppression rate reached 31%.
The trials enrolled more than 1,800 participants from 29 countries. The safety and tolerability profile was consistent with previous studies; the most common adverse events were injection site erythema, local pain, and temporary increases in liver enzyme levels.
Current standard therapies for CHB — nucleos(t)ide analogues — typically require lifelong treatment and achieve functional cure rates in less than 1% of patients. CHB affects more than 250 million people worldwide and accounts for approximately 56% of liver cancer cases globally.
Bepirovirsen is currently under priority review by the U.S. Food and Drug Administration and is also under regulatory review in Europe, Japan, and China. GSK expects the first regulatory decisions in the third quarter of 2026. If approved, bepirovirsen has the potential to become the first finite, six-month therapeutic option for CHB and to serve as a backbone for future sequential treatment strategies. GSK licensed bepirovirsen from Ionis and collaborated with them on its development.