GSK plc has announced that Japan’s Ministry of Health, Labour and Welfare has accepted for review a new drug application for bepirovirsen, an investigational antisense oligonucleotide, for the treatment of adults with chronic hepatitis B.
The submission marks the first regulatory filing globally for the therapy and will undergo expedited review under Japan’s SENKU designation, granted in August 2024 to support innovative medicines addressing high unmet medical needs.
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 a leading cause of liver cancer and is associated with approximately 1.1 million deaths annually, including around 4,000 deaths each year in Japan. Current standard treatment with nucleos(t)ide analogues often requires lifelong therapy and delivers low functional cure rates, typically around 1 percent. Functional cure refers to sustained undetectable levels of hepatitis B virus DNA and hepatitis B surface antigen in the blood for at least 24 weeks after stopping treatment, allowing immune control without medication. Achieving functional cure is associated with a significant reduction in the risk of long-term liver complications, including liver cancer, an estimated 56 percent of which globally are linked to chronic hepatitis B.
The Japanese regulatory submission is supported by data from the pivotal Phase III B-Well 1 and B-Well 2 trials, global, multi-centre, randomised, double-blind, placebo-controlled studies conducted across 29 countries. The trials evaluated efficacy, safety, pharmacokinetics and durability of response in non-cirrhotic patients with chronic hepatitis B who were receiving nucleos(t)ide analogue therapy and had baseline hepatitis B surface antigen levels of 3,000 IU/ml or lower. The primary endpoint measured the proportion of participants achieving functional cure in patients with baseline antigen levels at or below this threshold, while a key secondary endpoint assessed outcomes in those with levels of 1,000 IU/ml or lower.
Results showed that bepirovirsen in combination with standard of care achieved statistically significant and clinically meaningful improvements in functional cure rates compared with standard treatment alone across all ranked endpoints. Greater effects were observed in patients with lower baseline antigen levels. The therapy demonstrated an acceptable safety and tolerability profile consistent with earlier studies. Full data from the programme are expected to be presented at a scientific congress and submitted for peer-reviewed publication in 2026.
Bepirovirsen is designed to target and degrade the genetic material of the hepatitis B virus, including messenger RNA and pregenomic RNA, thereby inhibiting viral replication, reducing circulating hepatitis B surface antigen levels and potentially restoring immune control. It is also being evaluated as a potential backbone therapy in sequential treatment strategies aimed at broadening access to functional cure across wider patient populations.
The therapy was licensed by GSK from Ionis Pharmaceuticals and developed in collaboration. In addition to Japan’s SENKU designation, bepirovirsen has received Fast Track designation from the United States Food and Drug Administration and Breakthrough Therapy designation in China.
