On 20 October 2026, the US Food and Drug Administration approved Hibsago, the first FDA-approved antisense oligonucleotide for chronic hepatitis B.
Chronic hepatitis B infection can lead to serious liver disease, including cirrhosis, increasing the risk of liver cancer. It is a long-term liver infection caused by HBV. Hibsago works by targeting the genetic aspects of the HBV virus that it uses to make copies of itself and viral proteins. Hence, it helps in reducing the amount of virus and hepatitis B surface antigen in the body.
The drug is administered as an injection in combination with a patient's existing hepatitis B medication. The eligible patients must be adults without cirrhosis, who are six months into the antiviral medication, have suppressed levels of hepatitis B virus (HBV) and meet specific criteria for hepatitis B surface antigen (HBsAg).
Hibsago carries a boxed warning for serious liver reactions and thrombocytopenia, or low platelet counts, which can increase the risk of potentially life-threatening bleeding. The FDA also warns about worsening kidney function, serious inflammatory reactions such as vasculitis, and serious risks associated with improper injection administration. Common side effects, excluding laboratory abnormalities, include injection site reactions, fever, fatigue and headache. Patients require regular blood tests and follow-up with their healthcare provider before and during treatment to monitor these risks.
Hibsago was evaluated in two clinical trials, both of which followed stringent eligibility criteria. As specified in study protocols, patients were enrolled only if they met the following inclusion criteria:
had a negative cirrhosis diagnosis
had been receiving HBV antiviral therapy for at least 6 months
had suppressed HBV levels in the blood
had HBsAg levels ≤3000 IU/mL, as determined by an FDA-authorized test.¹
The FDA also approved the Roche Elecsys HBsAg II quant II RxDx assay as a companion diagnostic to assist with patient selection and monitoring throughout treatment.¹
The Hibsago clinical study was conducted in 2 randomized, double-blind, placebo-controlled phase 3 trials. Both the cycles evaluated the effects of bepirovirsen in adults with noncirrhotic chronic HBV infection receiving stable nucleos(t)ide analogue therapy.
The study was designed to be conducted in two phase 3 trials: B-Well 1 and B-Well 2. In the trials, approximately 24% of patients receiving the bepirovirsen intervention met the criteria to discontinue their existing antiviral medication, compared with none receiving placebo. 24 weeks after stopping all treatment, 19% of bepirovirsen recipients achieved a functional cure.
Wendy Carter, DO, acting director of the Office of Infectious Diseases in the FDA's Center for Drug Evaluation and Research, in an empathetic remark in the FDA’s recent press release, mentioned that many people who are diagnosed with chronic hepatitis B take antiviral medication for years just to keep the virus suppressed. For such people, Hibsago might be a boon as it brings the possibility of controlling the virus after all chronic HBV treatment has ended.
Participants were randomly assigned to receive 300 mg of subcutaneous bepirovirsen or placebo weekly for 24 weeks. At week 48, the eligible patients discontinued their routine antiviral therapy.
Patients continued their existing nucleos(t)ide analogue therapy for at least 24 weeks after their final Hibsago injection. At week 48, eligible patients discontinued this therapy, and the researchers assessed functional cure at week 72, 24 weeks after treatment cessation.
At week 72, functional cure was achieved by 20% of patients receiving bepirovirsen in B-Well 1 (127 of 650), compared with none of 328 placebo recipients. In B-Well 2, the corresponding rates were 19% (106 of 570) and 0% (0 of 286).
| Outcome at Week 72 | B-Well 1: Bepirovirsen | B-Well 1: Placebo | B-Well 2: Bepirovirsen | B-Well 2: Placebo |
|---|---|---|---|---|
| Participants achieving functional cure | 127/650 | 0/328 | 106/570 | 0/286 |
| Functional cure rate | 20% | 0% | 19% | 0% |
Across both trials, 233 of 1,220 participants (approximately 19%) receiving bepirovirsen achieved a functional cure, compared with none of the 614 participants receiving placebo.
A functional cure means that HBV DNA remains below the lower limit of quantification and hepatitis B surface antigen (HBsAg) is undetectable for at least 24 weeks after treatment ends. This does not mean that the virus is completely eliminated from the patient’s body or that the condition will never return.
Stopping antiviral therapy does not eliminate the need for follow-up. The product information warns that severe exacerbations of HBV infection can occur after discontinuing existing antiviral medication. Patients who discontinue this medication after completing Hibsago treatment require frequent monitoring for at least one year to detect worsening infection and assess whether antiviral treatment needs to be restarted.
Reference:
U.S. Food and Drug Administration. “FDA Approves First-of-Its-Kind Chronic Hepatitis B Treatment.” October 20, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-its-kind-chronic-hepatitis-b-treatment.
Hou J, Lim SG, Buti M, et al. “Phase 3 Results of Bepirovirsen Treatment for Chronic Hepatitis B Virus Infection.” New England Journal of Medicine. Published online May 28, 2026. https://doi.org/10.1056/NEJMoa2515131.
(Rh/MF/MSM)