Bepirovirsen produced sustained clearance of hepatitis B virus and hepatitis B surface antigens.
Bepirovirsen (GSK), an investigational antisense oligonucleotide, produced sustained clearance of hepatitis B virus (HBV) and hepatitis B surface antigens (HBsAg) in patients on concurrent nucleoside/nucleotide analogues (NA) and in patients not-on-NA therapy, according to results from the B-Clear phase 2B trial.
The trial found potential in bepirovirsen as a potential monotherapy or in combination with NAs, which could result in functional cure, according to GSK. Additionally, the trial identified a potential patient subgroup who are more likely to benefit from treatment with bepirovirsen.
“[The] results from the B-Clear study are a promising step forward for the approximately 300 million people living with chronic hepatitis B,” said Chris Corsico, SVP, Development, GSK, in a press release. “We look forward to confirming these findings for bepirovirsen in our phase 3 study starting next year, as well as exploring potential sequential therapy options with the aim of helping more people living with [chronic hepatitis B] achieve functional cure.”
Bepirovirsen is designed to specifically recognize the RNA that HBV uses to replicate in infected liver cells and to make the viral antigens that facilitate the chronicity of the virus by helping to avoid being cleared by the immune system. Bepirovirsen is also able to stimulate immune responses via Toll-like receptor 8 (TLR8), which may enable the immune system to achieve durable clearance of HBV from circulating blood.
The B-Clear phase 2b trial investigated the efficacy and safety of 12 or 24 weeks of bepirovirsen in people with chronic HBV on stable NA treatment or not on NA treatment at the start of the study. A loading dose of bepirovirsen at days 4 and 11 at a dose of 300 mg per week for 24 weeks resulted in 9% of patients on NA and 10% of patients not on NA achieving the primary endpoint of HBsAg levels below the Lower Limit of Detection and HBV DNA levels below the Lower Limit of Quantification.
Patients with low baseline HBV surface antigen levels had the best response to treatment with bepirovirsen in treatment arm 1, with 16% of patients on NA and 25% of patients not on NA achieving the primary endpoint.
There were no safety signals identified that would preclude further development. Adverse events (AEs) leading to treatment discontinuation occurred in 17 participants overall. Serious AEs were reported in 6 participants on NA and 11 participants not on NA.
“Chronic hepatitis B affects millions of people worldwide and is notoriously difficult to treat,” professor Man-Fung Yuen, principal investigator and chief of the Division of Gastroenterology and Hepatology, Queen Mary Hospital, The University of Hong Kong, said in a press release. “The promising data from the B-Clear study offer the potential for a chance of functional cure for the millions for people who are chronically infected with the virus, particularly for those with low baseline HBsAg levels.”
Positive data for bepirovirsen from B-Clear phase IIb trial presented at American Association for the Study of Liver Diseases’ Meeting with simultaneous publication in the New England Journal of Medicine. GSK. November 8, 2022. Accessed November 9, 2022. https://www.gsk.com/en-gb/media/press-releases/positive-data-for-bepirovirsen-from-b-clear-phase-iib-trial/