GSK and Ionis win first FDA approval for hepatitis B functional cure
The FDA has approved GSK and Ionis's RNA-based drug Hibsago, offering a functional cure for chronic hepatitis B in adults without cirrhosis after a six-month treatment course.
GSK and Ionis Pharmaceuticals received U.S. FDA approval for Hibsago on October 21, 2026. The RNA-based drug is the first therapy to offer a functional cure for chronic hepatitis B in adults without cirrhosis. The approval, granted under priority review and Breakthrough Therapy Designation, is for use alongside standard antiviral therapies in certain adults with chronic hepatitis B infections who have not developed cirrhosis. GSK licensed the drug, also known as bepirovirsen, from Ionis in 2019 under a collaborative development agreement. Ionis received an upfront payment, license fee, and milestone payments, and is eligible for tiered royalties of 10-12% on net sales.
Clinical criteria and treatment regimen
Hibsago is approved for adults with chronic hepatitis B who have been on nucleoside analogue therapy for at least six months, have suppressed hepatitis B virus DNA levels, and have hepatitis B surface antigen levels at or below 3000 IU/ml as determined by an FDA-authorized test. The six-month treatment regimen involves periodic injections, with all but the first dose potentially self-administered at home.
Efficacy and functional cure definition
The approval was based on Phase 3 B-Well trial data published in The New England Journal of Medicine. The trials demonstrated a functional cure, defined as undetectable HBV DNA and HBsAg for at least 24 weeks after stopping all treatment, in 19% of participants receiving bepirovirsen. This result compares to less than 1% in the placebo group receiving standard of care alone. Efficacy varied based on baseline antigen levels.
| HBsAg Level at Baseline | Functional Cure Rate | Participants Achieving Cure |
|---|---|---|
| ≤3000 IU/ml | 19% | 233 of 1,220 |
| ≤1000 IU/ml | 26% | 200 of 768 |
Exploratory analyses showed bepirovirsen reduced HBsAg to very low levels in a majority of participants in the more responsive subgroup. GSK estimates 1.7 million people in the U.S. and 240 million worldwide have chronic hepatitis B infections, with the ≤1000 IU/ml subgroup representing approximately 45% of diagnosed cases globally.
Safety and monitoring requirements
The drug carries safety warnings for on-treatment hepatic flares and thrombocytopenia, which can be life-threatening. The FDA labeling notes the potential for sudden spikes in liver enzymes and low platelet counts. The most frequently observed adverse events were injection site reactions and a temporary rise in liver enzymes.
Hibsago is contraindicated in patients with acute hepatic impairment or any stage of cirrhosis and in those with a pre-treatment platelet count below 100 x 10⁹/L. Patients must be monitored with weekly lab tests, and treatment must be discontinued if platelet count falls below 50 x 10⁹/L.
Hibsago is an RNA-based medicine designed to stop viral replication and stimulate an immune response. It has already been approved in Japan and is under regulatory review in China and Europe. Analysts project peak annual sales of around $3 billion for the drug. GSK plans to advance regulatory submissions for bepirovirsen across multiple geographies with key decisions anticipated in the coming months.
