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The approval follows results from the phase 3 B-Well 1 and B-Well 2 trials, in which 24% of patients receiving bepirovirsen met criteria to discontinue their existing antiviral medication, compared with none receiving placebo. At 24 weeks after stopping all treatment, 19% of bepirovirsen recipients achieved a functional cure, defined by sustained HBV DNA suppression below the lower limit of quantification and undetectable hepatitis B surface antigen (HBsAg).¹,²
“For many people living with chronic hepatitis B, treatment can mean taking antiviral medication for years to keep the virus suppressed,” Wendy Carter, DO, acting director of the Office of Infectious Diseases in the FDA's Center for Drug Evaluation and Research, said in a statement. “Hibsago provides a new treatment approach that gives some patients the possibility of maintaining control of the virus after all chronic HBV treatment has ended.”¹
The indication covers adults without cirrhosis who have received HBV antiviral therapy for at least 6 months, have suppressed HBV levels in the blood, and have HBsAg levels ≤3000 IU/mL, as determined by an FDA-authorized test.¹
The FDA also authorized the Roche Elecsys HBsAg II quant II RxDx assay as a companion diagnostic to aid patient selection and monitoring throughout treatment.¹
Bepirovirsen is administered by subcutaneous injection for up to 24 weeks alongside existing HBV antiviral therapy. Patients continue their existing medication for at least 24 weeks after the final bepirovirsen injection and may subsequently discontinue treatment if they meet specified clinical and laboratory criteria.¹
As an antisense oligonucleotide, bepirovirsen targets HBV RNA transcripts involved in viral replication and protein production, including HBsAg. By reducing these viral components, the treatment is intended to help patients achieve sustained viral control after discontinuing therapy.¹,²
The approval was supported by 2 randomized, double-blind, placebo-controlled phase 3 trials evaluating bepirovirsen in adults with noncirrhotic chronic HBV infection receiving stable nucleos(t)ide analogue therapy. Participants were assigned to receive 300 mg of subcutaneous bepirovirsen or placebo weekly for 24 weeks, with eligible patients discontinuing background antiviral therapy at week 48.²
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).²
Functional cure required sustained HBV DNA levels below the lower limit of quantification and HBsAg loss for at least 24 weeks after discontinuing all treatment. Although these findings demonstrate the potential for treatment-free viral control, functional cure does not necessarily indicate complete eradication of HBV or establish lifelong durability.²
Before the approval, Tatyana Kushner, MD, a hepatologist at Weill Cornell Medicine, joined Liver Lineup hosts Kimberly Brown, MD, and Nancy Reau, MD, to unpack the phase 3 B-Well 1 and B-Well 2 data behind bepirovirsen.
The conversation covers how HBsAg quantification may help identify eligible patients and what rollout could look like in practice, including ALT and renal monitoring, access, and renewed attention to HBV screening.
Listen to the full episode
Bepirovirsen carries a boxed warning for serious liver reactions and thrombocytopenia, or low platelet counts, which can increase the risk of potentially life-threatening bleeding.¹
Additional warnings include worsening kidney function, serious inflammatory adverse reactions such as vasculitis, and risks associated with improper injection administration. The FDA advises regular blood testing and clinical follow-up before and during treatment to monitor for these complications.¹
In pooled safety analyses from B-Well 1 and B-Well 2, adverse events occurred in 91% of bepirovirsen recipients and 73% of placebo recipients. Serious adverse events were reported in 7% and 4%, respectively. During the treatment period, grade ≥3 adverse events occurred in 16% of bepirovirsen recipients and 3% of placebo recipients, with elevated alanine aminotransferase levels representing the most common grade 3 event in the bepirovirsen group (6%).²
The most common adverse reactions reported by the FDA, excluding laboratory abnormalities, were injection site reactions, fever, fatigue, and headache.¹
The FDA granted bepirovirsen Fast Track and Breakthrough Therapy designations, as well as Priority Review. The approval was granted to GSK plc.¹
