GSK Gains FDA Approval for Hibsago After Positive B-WELL Trials

GSK has received US Food and Drug Administration (FDA) approval for Hibsago (bepirovirsen), an antisense oligonucleotide for chronic hepatitis B (CHB) in eligible adults receiving nucleos(t)ide analogue reverse transcriptase inhibitor (NrtI) therapy. The approval covers adults without cirrhosis who have received NrtI treatment for at least six months, have suppressed hepatitis B virus (HBV) DNA and have baseline hepatitis B surface antigen (HBsAg) levels of 3,000 IU/mL or lower, confirmed using an FDA-authorised test.

The approval was supported by the Phase III B-WELL 1 and B-WELL 2 trials, in which bepirovirsen produced higher functional cure rates than placebo. However, the results also show that most participants did not achieve functional cure, highlighting the importance of patient selection and continued monitoring. The FDA granted the medicine Priority Review, Breakthrough Therapy and Fast Track designations.

B-WELL Phase III Trials Demonstrate Functional Cure

Pooled results from B-WELL 1 (NCT05630807) and B-WELL 2 (NCT05630820) showed functional cure in 19% of participants receiving bepirovirsen (233/1,220), compared with none of the 614 participants receiving placebo. Both trials met their primary endpoints, demonstrating statistically significant improvements over placebo in adults with baseline HBsAg levels of 3,000 IU/mL or lower.

In a key secondary endpoint, functional cure was achieved in 26% of participants with baseline HBsAg levels of 1,000 IU/mL or lower (200/768), compared with none of the 393 participants receiving placebo. GSK estimates that this subgroup represents approximately 45% of diagnosed CHB cases globally.

Functional cure was assessed 24 weeks after all treatment had stopped and required undetectable HBV DNA and HBsAg levels for at least 24 weeks. The distinction is important because the outcome reflects sustained viral control after treatment discontinuation, rather than simply a reduction in viral markers during therapy.

Exploratory analyses at Week 72 found that HBsAg levels decreased to 100 IU/mL or lower in 49% of participants in the overall bepirovirsen group (598/1,220). The proportion was 62% among participants with baseline HBsAg levels of 1,000 IU/mL or lower (476/768). These biomarker findings support the treatment’s biological activity but should not be interpreted as equivalent to achieving functional cure.

Treatment Course and Safety Considerations

Hibsago is administered by subcutaneous injection for up to 24 weeks. Patients continue their existing NrtI therapy during treatment and for at least 24 weeks after the final Hibsago injection. Some patients may subsequently stop their existing antiviral medicine if they meet specified clinical and laboratory criteria.

The FDA prescribing information carries a boxed warning for on-treatment hepatic flares and thrombocytopenia, which can cause potentially life-threatening bleeding. Other warnings include worsening renal function, serious inflammatory and immune-mediated reactions, and risks associated with improper administration. Liver function, platelet counts and kidney function require appropriate assessment and monitoring before and during treatment.

In the B-WELL trials, the most frequently observed adverse events reported by GSK included injection-site erythema, local pain and transient increases in liver-enzyme levels. These trial observations should be distinguished from the serious risks described in the FDA-approved prescribing information.

How Bepirovirsen Works

Bepirovirsen is an antisense oligonucleotide designed to target HBV genetic material, reducing viral RNA and the production of viral proteins, including HBsAg. Lowering these viral markers may help the immune system maintain control of the infection after treatment ends. However, functional cure is not achieved by every patient, and durable control must be assessed through follow-up.

GSK licensed bepirovirsen from Ionis Pharmaceuticals and collaborated with the company on its development. The medicine is also approved in Japan, according to GSK.

Clinical Significance

The approval introduces a new treatment approach for selected adults whose HBV replication is already suppressed with existing antiviral therapy. The 19% functional cure rate represents a meaningful clinical result, while the higher response in participants with lower baseline HBsAg levels suggests that baseline viral markers may identify patients most likely to benefit.

Nevertheless, the findings do not establish that all eligible patients can discontinue antiviral therapy. The boxed warning and requirements for laboratory monitoring also mean that treatment selection and follow-up will remain important components of care. The clinical value of bepirovirsen will depend on its ability to produce sustained viral control in appropriately selected patients while managing these risks.

Reference

Hibsago (bepirovirsen) approved in the US for the treatment of chronic hepatitis B (CHB), GSK, 21 October 2026

FDA Approves First-of-Its-Kind Chronic Hepatitis B Treatment, US FDA, 20 October 2026

Study of Bepirovirsen in Nucleos(t)Ide Analogue-treated Participants with Chronic Hepatitis B (B-Well 1), ClinicalTrials.gov ID NCT05630807

Study of Bepirovirsen in Nucleos(t)Ide Analogue-treated Participants with Chronic Hepatitis B (B-Well 2), ClinicalTrials.gov ID NCT05630820