Positive Results from B-Clear Phase IIb Trial for Bepirovirsen in Chronic Hepatitis B Treatment

The B-Clear phase IIb trial evaluated the safety and efficacy of bepirovirsen, an investigational antisense oligonucleotide, for treating chronic hepatitis B (CHB). Results published in the New England Journal of Medicine indicated that bepirovirsen could lead to a functional cure, with sustained clearance of hepatitis B surface antigen (HBsAg) and HBV DNA in patients both on and not on nucleoside/nucleotide analogues (NA) therapy.

A functional cure for CHB means the virus is undetectable in blood and controllable by the immune system without medication. Current treatments, primarily NA therapy, suppress but rarely clear the virus, often requiring lifelong treatment. The trial identified a patient subgroup with low baseline HBsAg levels that responded best to bepirovirsen, suggesting a targeted approach could enhance treatment efficacy.

The trial involved patients receiving either 12 or 24 weeks of bepirovirsen treatment, with a loading dose at days 4 and 11. The 24-week treatment arm showed 9% of patients on NA and 10% not on NA achieved the primary outcome of HBsAg and HBV DNA levels below detection limits. Notably, patients with low baseline HBsAg levels had higher response rates, with 16% on NA and 25% not on NA achieving the primary outcome.

GSK is planning a Phase III trial for bepirovirsen in H1 2023 and exploring sequential treatment options to increase the functional cure rate. These include combining bepirovirsen with pegylated interferon and GSK’s chronic hepatitis B targeted immunotherapy.

The B-Clear trial's findings were presented at the American Association for the Study of Liver Diseases’ Liver Meeting 2022, highlighting the potential of bepirovirsen to significantly impact CHB treatment strategies. With approximately 300 million people worldwide living with CHB, the development of effective treatments like bepirovirsen represents a critical advancement in combating this global health threat.