Japan first approval for GSK’s bepirovirsen for CHB

GSK has announced that Japan’s Ministry of Health, Labour and Welfare (MHLW) has approved Hibsago (bepirovirsen), an antisense oligonucleotide (ASO), as a functional cure in chronic hepatitis B (CHB) virus infection in adult patients who have received at least six months of prior nucleos(t)ide analogue therapy and meet pre-defined viral markers.

CHB is a major public health challenge and a leading cause of liver cancer globally. Chronic hepatitis B occurs when the immune system is unable to clear the hepatitis B virus, resulting in long-lasting infection that affects more than 240 million people worldwide. In Japan, nearly one million people live with the disease, which contributes to around 4,000 deaths annually. The Japanese government has demonstrated strong commitment to tackling CHB including through nationwide screening and treatment programmes.

This is the first global regulatory approval for bepirovirsen, and it is the first and only functional cure in CHB to be approved in Japan. The approval was supported by results from the B-Well trials, showing ‘unprecedented’ functional cure rates of 19% in adults with ≤3000 IU/ml HBsAg, compared to current standard of care, which typically only achieves a 1% functional cure rate after one year of treatment.

Functional cure occurs when the hepatitis B virus DNA and viral protein – HBsAg – are undetectable for at least 24 weeks after stopping all treatment. This indicates the disease is controlled by the immune system without medication. A loss in HBsAg is associated with up to an 89% reduction in risk of liver cancer and a 62% reduction in risk of all-cause mortality.

The B-Well trials showed an acceptable safety and tolerability profile consistent with other studies of bepirovirsen. The three most frequently observed adverse events were injection site erythema, local pain, and temporary rise in the blood level of a liver enzyme.

GSK licensed bepirovirsen from Ionis and collaborated with them on its development. This approval was accelerated by Japan’s SENKU designation, granted to innovative medicines with potential to address high unmet medical need. Bepirovirsen has also been recognised by global regulatory authorities for its innovation and potential to address significant unmet need in hepatitis B, with Fast Track and Breakthrough Designations from the US FDA, and Breakthrough Therapy and Priority Review designation in China.

The data from the B-Well trials was presented at the European Association for the Study of the Liver (EASL) congress, and simultaneously published in the New England Journal of Medicine. GSK continues to advance regulatory submissions for bepirovirsen across multiple geographies with decisions, including the US, expected in the coming months.

China will be a big market for bepirovirsen, and the company has enlisted the aid of Sino Biopharm – via its subsidiary Chia Tai Tianqing Pharma (CTTQ) – to help it roll out the drug there as quickly as possible if it gets approval. China's National Medical Products Administration (NMPA) started a review in March.

Tony Wood, chief scientific officer at GSK, commented: “For the first time, a treatment approved for functional cure is available to people living with chronic hepatitis B in Japan with Hibsago. After 6-months of treatment with Hibsago, patients could be freed from life-long therapy and reduce their risk of long-term liver complications. This is a major advance for CHB management and our innovative hepatology portfolio, and we look forward to further regulatory decisions in other countries.”

GSK has a growing hepatology pipeline, harnessed by the science of the immune system and advanced technologies, with a focus on chronic hepatitis B, metabolic dysfunction-associated steatohepatitis (MASH) and alcohol-associated liver disease (ALD).