FDA Approves Bepirovirsen, First Antisense Therapy for Chronic Hepatitis B

The FDA approved Hibsago (bepirovirsen; GSK), the first antisense oligonucleotide for chronic hepatitis B, for use with a nucleos(t)ide analogue in adults without cirrhosis, the agency announced October 20, 2026.¹ The regimen aims to let some patients stop all hepatitis B therapy while keeping the virus controlled.

“For many people living with chronic hepatitis B, treatment can mean taking antiviral medication for years,” Wendy Carter, DO, acting director of the Office of Infectious Diseases in the FDA Center for Drug Evaluation and Research, said in the FDA announcement.¹ “This approval represents an important advance for people living with this serious disease.”

Eligible patients have taken nucleos(t)ide analogue therapy for at least 6 months, have suppressed HBV DNA, and have hepatitis B surface antigen (HBsAg) levels of 3000 IU/mL or less, as measured by an FDA-authorized test.^1,2 The FDA also authorized the Roche Elecsys HBsAg II quant II RxDx assay to select patients and monitor treatment. Hibsago received Fast Track, Breakthrough Therapy, and Priority Review designations.

Hibsago B-Well 1 and B-Well 2 Functional Cure Results

Approval rested on 2 global, randomized, double-blind, placebo-controlled phase 3 trials, B-Well 1 and B-Well 2, which enrolled adults in 29 countries receiving nucleos(t)ide analogue therapy with HBsAg levels of 3000 IU/mL or less.^2,3 Both trials met the primary end point of functional cure, defined as undetectable HBV DNA and HBsAg for at least 24 weeks after stopping all treatment.

In GSK's pooled analysis of both trials, 19% of patients receiving bepirovirsen (233 of 1220) achieved functional cure, vs 0 of 614 receiving placebo.² In the key ranked secondary population, patients with baseline HBsAg of 1000 IU/mL or less, 26% (200 of 768) reached functional cure vs 0 of 393 receiving placebo.

The FDA reported 24% of bepirovirsen recipients met the criteria to stop their existing antiviral medication, compared with none receiving placebo.¹ In an exploratory analysis, 49% of patients overall (598 of 1220) had HBsAg of 100 IU/mL or less at week 72. The rate was 62% (476 of 768) among those with baseline levels of 1000 IU/mL or less.²

READ MORE: Preventing Hepatitis B Vertical Transmission: Insights From Peyton Thompson, MD, MSCR

Hibsago Dosing, Boxed Warning, and Platelet Monitoring

The regimen consists of subcutaneous Hibsago injections for up to 24 weeks alongside existing therapy.¹ Patients continue their antiviral medication for at least 24 weeks after the last injection. Each dose consists of 2 injections separated by at least 2 inches (5 cm), with injection sites rotated weekly.² Patients may self-administer after the first dose.

The prescribing information carries a boxed warning for on-treatment hepatic flares and thrombocytopenia.^1,2 According to GSK's summary of the label, ALT elevations of more than 20 to 40 times the upper limit of normal occurred with HBsAg decline, some with hyperbilirubinemia, most often within the first 12 weeks. Clinicians should monitor ALT and total bilirubin before and during treatment and should not start Hibsago in patients with acute hepatic impairment or cirrhosis.

Thrombocytopenia can occur suddenly and unpredictably and raises the risk of life-threatening bleeding.^1,2 Hibsago is contraindicated with platelet counts below 100 × 10⁹/L, and clinicians should check platelets before treatment and weekly during it. The label calls for permanent discontinuation if counts fall below 50 × 10⁹/L.

Other warnings include worsening renal function, serious inflammatory reactions such as vasculitis, and risks from improper administration. The most common adverse reactions, excluding laboratory abnormalities, were injection site reactions, pyrexia, fatigue, and headache.^1,2

“This is the start of a new era in treating people living with CHB,” Norah Terrault, chief of gastroenterology and hepatology at USC Keck Medical Center, said in a GSK statement.²

GSK estimates about 1.7 million people in the US live with chronic hepatitis B.² Japan has approved bepirovirsen, and the company expects decisions from additional regulators in the coming months.²

References

1. FDA approves first-of-its-kind chronic hepatitis B treatment. News release. FDA. October 20, 2026. Accessed October 21, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-its-kind-chronic-hepatitis-b-treatment

2. Hibsago (bepirovirsen) approved in the US for the treatment of chronic hepatitis B (CHB). News release. GSK. October 20, 2026. Accessed October 21, 2026. https://us.gsk.com/en-us/media/press-releases/hibsago-bepirovirsen-approved-in-the-us-for-the-treatment-of-chronic-hepatitis-b-chb/

3. Bepirovirsen phase 3 results offer potential cure for chronic hepatitis B. Contagion. June 17, 2026. Accessed October 21, 2026. https://www.contagionlive.com/view/bepirovirsen-phase-3-results-offer-potential-cure-for-chronic-hepatitis-b