GSK has announced positive pivotal data for bepirovirsen, its investigational antisense oligonucleotide (ASO) for the treatment of chronic hepatitis B (CHB). Results from the two phase 3 trials, B-Well 1 and B-Well 2, were simultaneously published in the New England Journal of Medicine and presented at the European Association for the Study of the Liver (EASL) congress.
Pooled data from both trials showed that six-month treatment with bepirovirsen achieved a statistically significant and clinically meaningful 19% functional cure response rate (233 of 1,220 vs. 0 of 614 in the placebo group) in the overall study population (adults with ≤3000 IU/ml hepatitis B surface antigen (HBsAg) level), meeting the primary endpoint.
In a key secondary endpoint, a functional cure rate of 26% (200 of 768 vs. 0 of 393 in the placebo group) was achieved in participants with ≤1000 IU/ml HBsAg level, a group that represents approximately 45% of diagnosed CHB cases globally.
The current standard of care typically requires lifelong therapy, with functional cure rates achieved in less than 1% of patients.
Functional cure occurs when the hepatitis B virus (HBV) DNA and HBsAg are undetectable in the blood for at least six months after stopping all treatment. This indicates the disease is controlled by the immune system without medication. A loss in HBsAg is also associated with an 89% reduction in risk of liver cancer and a 62% reduction in risk of all-cause mortality.
Notably, in an exploratory analysis, 49% of bepirovirsen recipients achieved a quantitative hepatitis B surface antigen (qHBsAg) of ≤100 IU/mL one year after the end of treatment. Medical literature has linked this level of low surface antigen with increased immune control and improved patient outcomes.
Moreover, 23% of all bepirovirsen recipients (283 of 1220 vs 0 of 614 in the placebo group) and 31% of bepirovirsen recipients with baseline HBsAg ≤1000 IU/mL (237 of 768 vs 0 of 393 in the placebo group) achieved a sustained HBV DNA lower limit of quantification (<LLOQ) at week 72 after stopping all treatment at week 48 in a key secondary endpoint.
The trials showed an acceptable safety and tolerability profile consistent with other studies of bepirovirsen. The three most frequently observed adverse events were injection site erythema, local pain and temporary rise in the blood level of a liver enzyme.
Tony Wood, Chief Scientific Officer at GSK, said: “CHB affects over 240 million people worldwide and accounts for over half of global liver cancer cases. For the first time, bepirovirsen offers the possibility of significantly better functional cure rates than the current standard of care, and the potential to reduce the risk of long-term liver complications, including cancer.”
Bepirovirsen is currently under priority review by the US Food and Drug Administration (FDA) with both Breakthrough and Fast Track Designation. It is also under review by regulatory authorities in Europe, Japan with SENKU designation and China with Breakthrough Therapy and Priority Review designation. GSK anticipates the first regulatory decisions in Q3 2026 and launch preparations are underway. In May 2026, GSK entered a strategic collaboration with Sino Biopharmaceutical that aims to accelerate patient access to bepirovirsen at launch in China.