GSK has announced that its investigational antisense oligonucleotide (ASO) bepirovirsen met its primary endpoint in two pivotal phase III trials, B-Well 1 and B-Well 2. These trials evaluated bepirovirsen for the treatment of chronic hepatitis B (CHB) in over 1,800 patients across 29 countries.
Chronic Hepatitis B Context
Chronic hepatitis B is a viral infection that affects more than 250 million people globally and is responsible for approximately 56% of liver cancer cases. It causes an estimated 1.1 million deaths annually. The current standard of care, nucleos(t)ide analogues, often necessitates lifelong therapy, with functional cure rates typically around 1%.
A functional cure for CHB is defined by the sustained loss of hepatitis B surface antigen (HBsAg) and undetectable hepatitis B virus (HBV) DNA for at least 24 weeks following a finite course of treatment. This allows the immune system to manage the infection without continuous medication and is linked to a reduced risk of long-term liver complications and mortality.
B-Well Trial Results
The B-Well trials demonstrated that bepirovirsen, when administered with standard of care, resulted in statistically significant and clinically meaningful functional cure rates. These rates were higher compared to standard of care alone. Statistical significance was observed across all ranked endpoints, with a more pronounced effect in patients who had baseline HBsAg levels of 1000 IU/ml or less. The trials also reported a safety and tolerability profile consistent with prior studies.
About Bepirovirsen
Bepirovirsen is an investigational triple-action antisense oligonucleotide designed to target and facilitate the degradation of the genetic components (RNA) of the hepatitis B virus. This mechanism aims to inhibit viral DNA replication, suppress HBsAg levels, and stimulate the immune system to achieve a durable response. GSK licensed bepirovirsen from Ionis.
Future Steps
Full data from the trials will be submitted for presentation at an upcoming scientific congress and publication in a peer-reviewed journal. These results will support global regulatory submissions to health authorities, with filings anticipated from Q1 2026. If approved, bepirovirsen could become the first finite, six-month therapeutic option for CHB and serve as a foundation for future sequential treatment strategies.