GSK announced that Japan’s Ministry of Health, Labour and Welfare (MHLW) has accepted for review a New Drug Application (NDA) for bepirovirsen, an investigational antisense oligonucleotide (ASO), for the treatment of adults with chronic hepatitis B (CHB).

Chronic hepatitis B remains a major global health burden, affecting more than 250 million people worldwide and nearly one million individuals in Japan. The disease is responsible for approximately 1.1 million deaths globally each year, including around 4,000 deaths annually in Japan. It is also estimated that nearly 56 percent of liver cancer cases worldwide are linked to CHB.

Current standard treatment with nucleos(t)ide analogues often requires lifelong therapy, while functional cure rates remain low at around 1 percent. Functional cure is defined as sustained, undetectable hepatitis B virus DNA and hepatitis B surface antigen (HBsAg) levels in the blood for at least 24 weeks after stopping therapy, allowing immune control without medication. Achieving functional cure significantly reduces the risk of long-term liver complications, including liver cancer.

The regulatory submission is supported by positive data from the global Phase III B-Well and B-Well 2 trials. The multicentre, randomised, double-blind, placebo-controlled studies were conducted across 29 countries and evaluated the efficacy, safety, pharmacokinetics and durability of functional cure in non-cirrhotic CHB patients receiving nucleos(t)ide analogues.

Results showed that bepirovirsen, combined with standard of care, achieved statistically significant and clinically meaningful improvements in functional cure rates compared with standard therapy alone. Higher cure rates were observed across all ranked endpoints, particularly among patients with lower baseline HBsAg levels. The therapy demonstrated an acceptable safety and tolerability profile consistent with earlier studies. Detailed data are expected to be presented at a scientific congress and submitted for peer-reviewed publication in 2026.

Bepirovirsen received SENKU designation in Japan in August 2024, enabling expedited regulatory review and reflecting its innovation and potential to address significant unmet medical needs. The therapy has also been granted Fast Track designation by the U.S. FDA and Breakthrough Therapy designation in China.

Bepirovirsen is a triple-action antisense oligonucleotide designed to target and degrade hepatitis B viral mRNA and pregenomic RNA. By inhibiting viral replication, reducing HBsAg levels and stimulating immune response, it aims to enable durable immune control of the infection. The therapy is also being evaluated as a potential backbone for future sequential treatment strategies to expand functional cure across broader patient populations.

GSK licensed bepirovirsen from Ionis Pharmaceuticals and has collaborated on its development. The investigational therapy is not currently approved anywhere in the world.