The US Food and Drug Administration (FDA) has approved bepirovirsen (Hibsago), the first antisense oligonucleotide therapy for chronic hepatitis B virus (HBV) infection, offering eligible adults the possibility of maintaining viral control after discontinuing antiviral treatment, according to FDA and GSK press releases.
The October 20 approval covers adults without cirrhosis who have received nucleos(t)ide analogue antiviral therapy for at least 6 months, have suppressed HBV DNA, and have hepatitis B surface antigen (HBsAg) levels of 3,000 IU/mL or less, as confirmed by an FDA-authorized test.
Bepirovirsen is administered alongside existing antiviral therapy and targets HBV RNA to reduce viral protein production. The FDA also authorized Roche's Elecsys HBsAg II quant II RxDx assay as a companion diagnostic to help identify eligible patients and monitor treatment.
Approval was supported by 2 randomized, double-blind, placebo-controlled phase 3 trials, B-Well 1 and B-Well 2, conducted across 29 countries. The trials compared bepirovirsen plus ongoing antiviral therapy with placebo plus antiviral therapy in adults with chronic HBV infection without cirrhosis.
The primary efficacy end point was functional cure, defined as sustained suppression of HBV DNA and undetectable HBsAg for at least 24 weeks after all treatment was discontinued.
In pooled results, 19% of patients receiving bepirovirsen (233 of 1,220) achieved functional cure, compared with 0% of placebo recipients (0 of 614). Among patients with baseline HBsAg levels of 1,000 IU/mL or less, the response rate was 26% (200 of 768), compared with 0% (0 of 393) receiving placebo.
Across both trials, 24% of bepirovirsen-treated patients met the criteria to discontinue their existing antiviral medication, compared with 0% of those receiving placebo. Treatment discontinuation was conditional on meeting clinical and laboratory criteria.
Bepirovirsen is administered by subcutaneous injection for up to 24 weeks, while existing antiviral therapy must continue for at least 24 weeks after the final injection. Patients may discontinue antiviral treatment only if they meet the specified stopping criteria.
The prescribing information carries boxed warnings for serious liver reactions as well as low platelet counts, including potentially life-threatening bleeding. Additional risks include worsening kidney function, serious inflammatory reactions such as vasculitis, and complications from improper injection.
The most common adverse reactions were injection-site reactions, fever, fatigue, and headache.
