GSK (GSK in the US) breakthrough hepatitis B therapy reaches Phase 3 trial primary endpoints, application for market approval imminent.

GSK (GSK.US) announced today that its investigational antisense oligonucleotide (ASO) therapy bepirovirsen, developed in collaboration with Ionis Pharmaceuticals, has shown positive results in two key phase 3 clinical trials B-Well 1 and B-Well 2 for the treatment of chronic hepatitis B virus (HBV). Both trials met their primary endpoints. Bepirovirsen demonstrated a statistically and clinically significant functional cure rate. GSK plans to initiate global regulatory submissions in the first quarter of 2026. Chronic hepatitis B is a major global health challenge, affecting over 250 million people, and is a leading cause of liver cancer. Current standard treatments based on nucleos(t)ide analogs often require long-term or lifelong therapy, but have a low functional cure rate, usually around 1%. B-Well 1 and B-Well 2 are global multicenter, randomized, double-blind, placebo-controlled trials designed to evaluate the efficacy, safety, pharmacokinetic characteristics, and durability of functional cure of bepirovirsen in chronic hepatitis B patients receiving nucleos(t)ide analog therapy with baseline HBsAg 3000 IU/ml. The primary endpoint was the proportion of patients achieving functional cure with baseline HBsAg 3000 IU/ml. A key secondary endpoint was the proportion of patients achieving functional cure with baseline HBsAg 1000 IU/ml. Functional cure was defined as loss of HBsAg and undetectable HBV DNA for at least 24 weeks after a limited course of treatment. The analysis showed that the B-Well trials met their primary endpoint, with bepirovirsen demonstrating a statistically significant and clinically meaningful functional cure rate. Bepirovirsen in combination with standard therapy significantly improved the functional cure rate compared to standard therapy alone. Statistically significant results were seen in all endpoints, including patients with baseline HBsAg 1000 IU/ml, where a stronger effect was observed. The trials also showed good safety and tolerability of bepirovirsen, consistent with previous study results. Bepirovirsen is an investigational ASO therapy with a triple-action mechanism designed to identify and destroy the genetic component (RNA) of the hepatitis B virus, potentially allowing the patient's immune system to regain control of the virus infection.