Japan approves GSK’s Hibsago (bepirovirsen), the first functional cure treatment for chronic hepatitis B, supported by Phase III B-Well data
Written By: Kalyani Boharapi,
M.Pharm (Reg. Affairs)
Reviewed By: Pharmacally Editorial Team
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 treatment for adults with chronic hepatitis B (CHB) who have received at least six months of prior nucleos(t)ide analogue therapy and meet predefined viral-marker criteria. The approval represents the first global approval for bepirovirsen and makes Hibsago the first and only approved functional cure treatment for CHB in Japan.
Chronic Hepatitis B Remains a Major Clinical Challenge
CHB is a major public health problem and a leading cause of liver cancer globally. In Japan, nearly one million people live with the disease, which contributes to approximately 4,000 deaths annually.
Current nucleos(t)ide analogue therapy often requires long-term or lifelong treatment and primarily suppresses viral replication rather than achieving functional cure. GSK reports that standard treatment typically achieves functional cure rates of around 1% after one year of treatment.
What Is Functional Cure in Chronic Hepatitis B?
Functional cure occurs when hepatitis B virus (HBV) DNA and hepatitis B surface antigen (HBsAg) become undetectable for at least 24 weeks after treatment has stopped. This indicates that the immune system can control the infection without ongoing medication.
Loss of HBsAg is associated with substantially lower risks of long-term complications. GSK cites associations with up to an 89% reduction in liver cancer risk and a 62% reduction in all-cause mortality.
B-Well Phase III Trials Demonstrate Functional Cure
The approval was supported by pooled results from the B-Well 1 (NCT05630807) and B-Well 2 (NCT05630820) Phase III trials. The global, multicentre, randomised, double-blind, placebo-controlled studies were conducted across 29 countries and evaluated efficacy, safety, pharmacokinetics and durability of functional cure in nucleos(t)ide analogue-treated adults with CHB and baseline HBsAg levels of ≤3,000 IU/mL.
After six months of treatment, bepirovirsen achieved a 19% functional cure rate in the overall study population, compared with 0% with placebo (233/1,220 vs 0/614; p<0.001), meeting the primary endpoint.
Higher Functional Cure Rate in Patients with Lower HBsAg
A key secondary endpoint showed a 26% functional cure rate among participants with baseline HBsAg levels of ≤1,000 IU/mL, compared with 0% in the placebo group (200/768 vs 0/393; p<0.001). This subgroup represents approximately 45% of diagnosed CHB cases globally.
Exploratory analyses also showed that 49% of bepirovirsen recipients in the overall population and 62% of those with baseline HBsAg ≤1,000 IU/mL had HBsAg levels reduced to ≤100 IU/mL at Week 72.
Bepirovirsen Targets HBV RNA
Bepirovirsen is an ASO designed to recognise and inhibit the production of HBV RNA. By reducing viral RNA and associated viral proteins, including HBsAg, the treatment is intended to support restoration of immune control and increase the likelihood of a durable response. GSK licensed bepirovirsen from Ionis and collaborated with the company on its development.
Safety Profile and Regulatory Development
The B-Well trials demonstrated an acceptable safety and tolerability profile consistent with previous studies. The most frequently observed adverse events included injection-site erythema, local pain and temporary increases in liver enzyme levels.
Japan’s approval was accelerated under the SENKU designation, which is intended for innovative medicines addressing high unmet medical need. Bepirovirsen has also received regulatory designations in the US and China. GSK is continuing regulatory submissions across multiple geographies, with a US decision expected in the coming months. Development of bepirovirsen for future sequential-treatment strategies is also ongoing.
Clinical Significance
The approval of Hibsago introduces a finite treatment option with the potential to achieve functional cure in appropriately selected adults with CHB. The Phase III findings suggest that bepirovirsen may allow some eligible patients to discontinue long-term antiviral therapy following treatment, representing a potential shift from sustained viral suppression toward immune-controlled disease.
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About the Writer
Kalyani Boharapi (LinkedIn) is a pharmacy professional and healthcare writer currently pursuing an M.Pharm in Regulatory Affairs at Dr. D. Y. Patil College of Pharmacy, with interests in pharmaceutical regulations, drug development, and healthcare innovation. She has academic exposure to dossier preparation, scientific writing, and regulatory documentation. Kalyani has also completed certification courses in Generative AI, AI in Pharma, and Bioinformatics, and actively participates in pharmaceutical conferences to stay updated with emerging trends and advancements in the healthcare and pharmaceutical industry.