The US Food and Drug Administration on Oct. 20 approved bepirovirsen injection (Hibsago, GSK), in combination with existing antiviral therapy, for certain adults with chronic hepatitis B virus (HBV) infection who do not have cirrhosis. It is the first FDA-approved antisense oligonucleotide for chronic hepatitis B.1
The indication covers adults who have received nucleoside or nucleotide analogue (NA) 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 determined by an FDA-authorized test.1,2
Alongside the approval, the FDA authorized the Roche Elecsys HBsAg II quant II RxDx assay as a companion diagnostic to help identify eligible patients and monitor treatment. Bepirovirsen targets HBV messenger RNA, reducing the production of viral proteins, including HBsAg, according to the FDA and the drug’s prescribing information.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 the announcement.1
The new treatment offers some patients the possibility of maintaining viral control after discontinuing all chronic HBV therapy, the FDA said.1
What the trials showed
The approval is based on B-Well 1 and B-Well 2, two identical, randomized, double-blind, placebo-controlled phase 3 trials that GI & Hepatology News reported on in July. The trials enrolled 1,838 adults without cirrhosis at centers in 29 countries. Participants were receiving stable NA therapy and had baseline HBsAg levels greater than 100 IU/mL and up to 3,000 IU/mL.2-4
Patients were assigned 2:1 to bepirovirsen or placebo for 24 weeks while continuing their existing antivirals. Those who met prespecified criteria for sustained HBsAg loss and HBV DNA suppression could discontinue NA therapy at week 48.2,3
Across both trials, 24% of bepirovirsen-treated patients (295 of 1,220) qualified to stop NA therapy, compared with none in the placebo group. At week 72, 19% (233 of 1,220) achieved the primary endpoint of functional cure, defined as sustained HBsAg loss and HBV DNA below the lower limit of quantification for at least 24 weeks after stopping all treatment. None of the 614 placebo recipients achieved that endpoint.2,3
Functional cure rates were 20% in B-Well 1 and 19% in B-Well 2. Patients with lower baseline HBsAg levels responded more favorably. Among those with HBsAg levels of 1,000 IU/mL or less, functional cure rates were 25% and 28%, respectively, compared with 10% and 5% among those with higher levels.3
The FDA-approved prescribing information also includes updated durability data through week 96. Of the 233 patients who achieved functional cure at week 72, 91% (211 patients) maintained their response through week 96, representing 48 weeks without HBV therapy. Among the 84 patients who stopped NA therapy but did not achieve or maintain functional cure through week 96, one met protocol-defined criteria to restart antivirals. Three additional patients restarted NA therapy without meeting those criteria.2
Longer follow-up remains necessary to establish whether these responses are sustained over several years, the investigators noted.3
Practical impact
For gastroenterologists and hepatologists managing chronic HBV, the approval introduces a potential route to antiviral discontinuation, but the FDA labeling also establishes specific requirements for patient selection, treatment administration, and monitoring.
Because the indication is limited to patients with HBsAg levels of 3,000 IU/mL or less, as determined by an FDA-authorized test, quantitative HBsAg testing is a prerequisite for eligibility.1,2 When GI & Hepatology News covered the phase 3 results in July, Tatyana Kushner, MD, MSCE, of Weill Cornell Medicine, noted that quantitative HBsAg testing had not traditionally been performed for most patients but would likely play a key role in identifying those most likely to benefit.4
The treatment regimen also differs substantially from standard oral NA therapy. According to the FDA-approved prescribing information, bepirovirsen is administered subcutaneously at 300 mg twice weekly during the first 2 weeks, followed by 300 mg once weekly through week 24. Each 300-mg dose requires two 150-mg injections. The labeling specifies that the first dose be administered under health care professional supervision, although patients or caregivers may administer subsequent doses after appropriate training.2
Under the approved regimen, patients remain on their existing NA therapy throughout bepirovirsen treatment and for at least 24 weeks after the final injection.2
The FDA labeling states that NA discontinuation may then be considered in patients who are HBeAg-negative, have HBV DNA below 20 IU/mL, have undetectable HBsAg, and have ALT levels no more than twice the upper limit of normal. Patients taking NA therapy for HIV-1 coinfection must not stop it unless their HIV health care provider directs them to, according to the labeling.2
For patients who discontinue NA therapy, the labeling calls for frequent monitoring of HBsAg, HBV DNA, and hepatic function for at least one year, followed by routine monitoring thereafter. The FDA warns that severe HBV exacerbations may occur after antiviral discontinuation.2
An early treatment response may also help predict the likelihood of functional cure. In a post hoc analysis reported in the prescribing information, 34% of patients whose HBsAg fell below 1 IU/mL by treatment week 12 achieved the primary endpoint, compared with 2% of those who did not reach that threshold. The FDA labeling states that early discontinuation of bepirovirsen may be considered if HBsAg remains at or above 1 IU/mL at week 12.2
Safety and monitoring requirements
Bepirovirsen carries boxed warnings for on-treatment hepatic flares and thrombocytopenia. According to the prescribing information, ALT elevations may exceed 20 to 40 times the upper limit of normal, occasionally with hyperbilirubinemia. The labeling also warns that platelet counts can decline suddenly and unpredictably, potentially causing life-threatening bleeding.2
The drug is contraindicated in patients with acute hepatic impairment, cirrhosis with Child-Pugh class A, B, or C impairment, or a pretreatment platelet count below 100 × 109/L.2
The FDA-approved labeling specifies an intensive laboratory monitoring schedule. It calls for platelet counts at least weekly throughout treatment; ALT and bilirubin testing weekly through week 12 and every other week thereafter through week 24; and estimated glomerular filtration rate monitoring every other week. Depending on laboratory results, the labeling provides for more frequent testing, treatment interruption, or dose modification.2
Other warnings include worsening kidney function, serious inflammatory and immune-mediated reactions such as vasculitis, and adverse reactions associated with improper injection technique. The prescribing information advises against use in patients with hepatitis D coinfection because of the potential for clinically significant hepatic flares.2
In the pooled phase 3 safety data, injection-site reactions occurred in 57% of bepirovirsen-treated patients vs 15% of placebo recipients during weeks 1 through 36. Other common adverse reactions included fever, fatigue, and headache. Approximately 3% of treated patients discontinued bepirovirsen because of adverse events, according to the prescribing information.2
During the 24-week treatment period, grade 3 or higher adverse events occurred in 16% of bepirovirsen recipients vs 3% of placebo recipients, with ALT elevations the most common severe event. The trial investigators reported that platelet counts and kidney function generally returned toward baseline after treatment ended.3
Questions remain about long-term benefit
The approval applies to a defined population, and the evidence has limitations. The pivotal trials excluded patients with cirrhosis; those with HIV, hepatitis C, or hepatitis D coinfection; and those with certain baseline kidney function or platelet abnormalities. Most participants were HBeAg-negative.2,3
Patients with baseline HBsAg levels above 3,000 IU/mL were also excluded, leaving the effectiveness of bepirovirsen in that population uncertain. Although the week-96 findings provide additional evidence of durable viral control, longer-term outcomes remain unknown.2,3
HBsAg loss does not end liver cancer surveillance for all patients. The AASLD/IDSA hepatitis B guideline suggests continued HCC surveillance after HBsAg loss for patients with cirrhosis or a family history of HCC, men who lose HBsAg after age 40, and women who lose it after age 50.5
The FDA granted bepirovirsen fast track and breakthrough therapy designations as well as priority review. The approval was granted to GSK plc.1
References
US Food and Drug Administration. FDA approves first-of-its-kind chronic hepatitis B treatment. News release. October 20, 2026. Accessed October 21, 2026.
GSK. Hibsago (bepirovirsen) injection, for subcutaneous use. Prescribing information. Revised October 2026. Accessed October 21, 2026.
Hou J, Lim SG, Buti M, et al; B-Well Study Group. Phase 3 results of bepirovirsen treatment for chronic hepatitis B virus infection. N Engl J Med. 2026;394(24):2395-2406. doi:10.1056/NEJMoa2515131.
Brunk D. One in five reach hepatitis B functional cure with finite bepirovirsen. GI & Hepatology News. July 16, 2026. Accessed October 21, 2026.
Ghany MG, Pan CQ, Lok AS, et al. AASLD/IDSA practice guideline on treatment of chronic hepatitis B. Hepatology. 2026;83(4):974-997. doi:10.1097/HEP.0000000000001549.