GSK and Ionis’ bepirovirsen ASO gains FDA breakthrough designation for chronic hepatitis B

Edited by Robert McTiernan··4 min read

GSK (LSE/NYSE: GSK) and its partner Ionis Pharmaceuticals (Nasdaq: IONS), headquartered in Carlsbad, California, announced that the US FDA has accepted for Priority Review the New Drug Application (NDA) for bepirovirsen, an antisense oligonucleotide (ASO) designed to inhibit hepatitis B virus (HBV) RNA transcripts, for the treatment of adults with chronic hepatitis B (CHB). The FDA simultaneously granted Breakthrough Therapy Designation (BTD) and set a Prescription Drug User Fee Act (PDUFA) target action date of October 26, 2026.

BTD adds to the Fast Track Designation bepirovirsen received in February 2024, providing intensive FDA guidance and organizational commitment from senior agency officials. Priority Review compresses the standard FDA review window from twelve months to six.

The regulatory submission rests on data from the Phase III B-Well 1 (NCT05630807) and B-Well 2 (NCT05630820) trials, global multicenter, randomized, double-blind, placebo-controlled studies conducted across 29 countries in nucleos(t)ide analogue (NA)-treated participants with CHB and baseline hepatitis B surface antigen (HBsAg) of 3,000 IU/mL or below. Both trials met their primary endpoint, demonstrating statistically significant functional cure rates — defined as undetectable HBsAg and HBV DNA for at least 24 weeks after stopping all treatment — for bepirovirsen plus standard of care versus standard of care alone. A key secondary endpoint evaluated functional cure in participants with baseline HBsAg at or below 1,000 IU/mL, where an even greater treatment effect was observed. Full numeric data are scheduled for presentation at the European Association for the Study of the Liver (EASL) 2026 Congress in May and simultaneous peer-reviewed publication.

Earlier Phase IIb data, published in the New England Journal of Medicine in November 2022, reported that the 300 mg/week bepirovirsen dose for 24 weeks produced functional cure in approximately 9–10% of participants versus 0% in the placebo group, against a background spontaneous functional cure rate of roughly 1% with NA monotherapy alone.

Bepirovirsen is also under regulatory review with the European Medicines Agency (EMA), China’s National Medical Products Administration (NMPA), and Japan’s Ministry of Health, Labour and Welfare (MHLW). The molecule has received Breakthrough Therapy Designation in China and SENKU Designation in Japan. GSK licensed bepirovirsen from Ionis in 2019 under a collaborative development and licensing agreement; Ionis is eligible to receive tiered royalties of 10–12% on net sales.

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Research context

CHB affects more than 250 million people globally and approximately 1.7 million in the US, causing around 1.1 million deaths annually, predominantly from cirrhosis and hepatocellular carcinoma. Current standard of care — NA agents such as tenofovir and entecavir — suppresses HBV DNA effectively but rarely eliminates HBsAg; functional cure rates under NA therapy remain at approximately 1% per year. No approved therapy has demonstrated the capacity to produce durable off-treatment viral control at a scale that would alter long-term liver-disease outcomes at a population level.

Bepirovirsen’s mechanism differs from approved NAs and from capsid assembly modulators or RNA interference (RNAi) agents in late-stage development. As an ASO, it binds HBV RNA transcripts to reduce production of all viral proteins encoded by the HBV genome, including HBsAg and HBV core antigen, while also engaging innate immune pathways. RNAi-based approaches such as JNJ-3989 (from Johnson & Johnson) and VIR-2218 (from Vir Biotechnology and Alnylam) target HBV RNA through a distinct RISC-mediated cleavage mechanism and are generally being evaluated in combination regimens rather than as monotherapy functional-cure candidates. The B-Well program is notable in that bepirovirsen was tested as an add-on to existing NA therapy rather than requiring cessation of background treatment, which has practical implications for patient management.

An ongoing Phase II B-United study is evaluating sequential daplusiran/tomligisiran followed by bepirovirsen in NA-treated CHB patients, exploring whether deeper initial HBsAg suppression with RNAi agents can improve bepirovirsen-mediated functional cure rates. A separate study, B-Focus (NCT06497504), is extending the bepirovirsen evaluation to HIV/HBV co-infected participants. Data from a B-Sure sub-analysis presented at the American Association for the Study of Liver Diseases (AASLD) meeting in November 2025 examined durability of functional cure following bepirovirsen plus sequential pegylated interferon, addressing the relapse rate of approximately two-thirds seen among initial responders in earlier studies, though granular numeric outcomes from that sub-analysis had not been publicly disclosed at the time of the AASLD presentation.

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