On October 20, the FDA cleared bepirovirsen, marketed as Hibsago, for use in adults battling chronic hepatitis B virus (HBV). This drug, created by GSK, represents a potential limited-duration solution that might allow some patients to maintain viral control after stopping long-term antiviral medications.
Eligible patients must have no cirrhosis, at least 6 months of prior nucleos(t)ide analog reverse transcriptase inhibitor (NrtI) therapy, suppressed HBV DNA, and HBV surface antigen (HBsAg) levels at or below 3,000 IU/mL as determined by an FDA-authorized test.
Bepirovirsen’s Mechanism of Action
Bepirovirsen functions as an antisense oligonucleotide that disrupts HBV by targeting the virus’s messenger RNA (mRNA). It latches onto a genetic sequence common to multiple HBV RNA forms, triggering the body’s natural RNase H1 enzyme to degrade the viral RNA.
This process reduces the production of viral DNA and proteins, including HBsAg. The drug can also attack RNA derived from persistent HBV DNA inside liver cells (cccDNA) and from HBV DNA integrated into the patient’s own genetic material.
Clinical Trials and Efficacy
Functional cure means sustained control of HBV without medication, rather than complete elimination of the virus. In the trials, patients received loading doses on days 4 and 11, then 300 mg subcutaneously once weekly for 24 weeks, in addition to their existing antiviral therapy.
The approved US dosing is 300 mg subcutaneously twice weekly during weeks 1 and 2, with 3 or 4 days between doses, followed by 300 mg once weekly during weeks 3 through 24. Each 300-mg dose requires two 150-mg injections.
Bepirovirsen received its first global approval in Japan in August 2026 for selected adults with chronic hepatitis B who had received at least 6 months of nucleoside or nucleotide analog treatment.
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The Japanese criteria include HBsAg ≤3,000 IU/mL and HBV DNA <90 IU/mL, in addition to prior antiviral treatment. The B-Well 1 and B-Well 2 trials were randomized, double-blind, placebo-controlled phase 3 studies enrolling adults with noncirrhotic chronic HBV infection on stable nucleos(t)ide analogue (NA) therapy.
Patients had to have HBsAg above 100 IU/mL and at or below 3,000 IU/mL, as well as HBV DNA <90 IU/mL and ALT ≤2 times the upper limit of normal at screening. The trials randomized 1,838 adults 2:1 to subcutaneous bepirovirsen (300 mg weekly) or placebo for 24 weeks while continuing background NA treatment.
Approximately 1,834 patients received at least one dose and were included in the efficacy analysis. Eligible patients stopped antiviral treatment at week 48. The primary endpoint was functional cure at week 72, defined as sustained HBsAg loss and HBV DNA below the quantification limit for at least 24 weeks after all treatment stopped.
Both trials met their primary endpoint. In B-Well 1, 127 of 650 patients (20%) receiving bepirovirsen achieved functional cure compared with none of the 328 participants receiving placebo.
Response was greater in participants with lower baseline HBsAg levels.
Among those with levels of 1,000 IU/mL or less, functional cure rates were approximately 25% and 28% in B-Well 1 and B-Well 2, respectively. At week 48, approximately 24% of bepirovirsen-treated patients in both B-Well 1 and B-Well 2 met laboratory-based criteria for discontinuing NA therapy.
Compared to patients receiving placebo, bepirovirsen-treated patients had higher rates of adverse events, including injection-site reactions and ALT elevations. The approved FDA labeling includes boxed warnings for on-treatment hepatic flares and thrombocytopenia.
