GSK plc has received approval from Japan’s Ministry of Health, Labour and Welfare (MHLW) for Hibsago (bepirovirsen), an Antisense Oligonucleotide (ASO), as a functional cure for Chronic Hepatitis B (CHB) in eligible adults. The approval marks the first global regulatory approval for bepirovirsen and makes Hibsago the first and only treatment approved in Japan specifically for a functional cure of CHB.

Hibsago is indicated for adults with chronic hepatitis B who have received at least six months of prior nucleos(t)ide analogue therapy and meet predefined viral-marker criteria.

Chronic hepatitis B remains a major global health challenge and a leading cause of liver cancer. In Japan, nearly one million people are estimated to live with CHB, which contributes to approximately 4,000 deaths annually. The Japanese government has implemented nationwide screening and treatment initiatives to address the disease burden.

The approval was supported by results from the global Phase 3 B-Well 1 and B-Well 2 trials, which evaluated bepirovirsen in adults with CHB who had previously received nucleos(t)ide analogue therapy.

Pooled results from the trials showed that six months of bepirovirsen treatment produced a 19 percent functional cure rate, with 233 of 1,220 participants achieving the primary endpoint compared with none of the 614 participants receiving placebo. The result was statistically significant, with p<0.001 in both studies.

Among participants with baseline hepatitis B surface antigen (HBsAg) levels of 1,000 IU/ml or less, the functional cure rate increased to 26 percent, with 200 of 768 participants achieving the endpoint compared with none of 393 participants in the placebo group. GSK said this subgroup represents approximately 45 percent of diagnosed CHB cases globally.

Functional cure was defined as undetectable hepatitis B surface antigen and viral DNA for at least 24 weeks after discontinuation of all treatment, indicating that the immune system is able to maintain control of the infection without ongoing medication.

Exploratory analyses also showed that 49 percent of participants in the overall study population achieved HBsAg levels of 100 IU/ml or less by the week 72 assessment. The proportion increased to 62 percent among participants with baseline HBsAg levels of 1,000 IU/ml or less.

Bepirovirsen is designed to target the RNA produced by hepatitis B virus and inhibit the production of viral proteins, including hepatitis B surface antigen. By reducing viral proteins and stimulating aspects of the immune response, the treatment is intended to help restore the body's ability to control the virus.

The Phase 3 trials reported an acceptable safety and tolerability profile consistent with previous studies of bepirovirsen. The most frequently observed adverse events included injection-site redness, local pain and temporary increases in blood levels of a liver enzyme.

The Japanese approval was accelerated through the SENKU designation, which is granted to innovative medicines that have the potential to address significant unmet medical needs.

“After six months of treatment with Hibsago, patients could be freed from life-long therapy and reduce their risk of long-term liver complications,” said Tony Wood, Chief Scientific Officer, GSK. He described the approval as a significant advance in CHB management and GSK’s hepatology portfolio.

GSK is continuing regulatory submissions for bepirovirsen in multiple markets, with regulatory decisions, including in the United States, expected in the coming months. The company is also investigating the potential use of bepirovirsen in future sequential treatment strategies.

The B-Well 1 and B-Well 2 trials were randomised, double-blind, placebo-controlled, multicentre studies conducted across 29 countries. They assessed the efficacy, safety, pharmacokinetics and durability of functional cure among adults with CHB receiving nucleos(t)ide analogue therapy.

Chronic hepatitis B occurs when the immune system fails to eliminate the hepatitis B virus, resulting in a persistent infection. The condition affects more than 240 million people globally and is associated with approximately 1.1 million deaths each year, with liver cancer representing one of its major complications.

While existing antiviral treatments can suppress the virus, many patients require long-term or lifelong therapy. Achieving a functional cure, therefore, remains a major objective in CHB treatment.

GSK licensed bepirovirsen from Ionis Pharmaceuticals and collaborated with the company on its development. The medicine has received regulatory recognition in several markets, including Fast Track and Breakthrough Therapy designations from the US FDA, Breakthrough Therapy and Priority Review designations in China, and SENKU designation in Japan.

GSK is continuing to expand its hepatology pipeline, focusing on chronic hepatitis B as well as Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Alcohol-associated Liver Disease (ALD), as part of its broader focus on immune-driven and fibro-inflammatory diseases.