FDA Approves Bepirovirsen, First ASO for Chronic Hepatitis B

The FDA approved bepirovirsen (Hibsago; GSK) injection in combination with existing antiviral therapy for certain adults with chronic hepatitis B virus (HBV) infection without cirrhosis, according to a news release from the FDA.

Bepirovirsen is the first antisense oligonucleotide (ASO) approved for chronic hepatitis B. Because it is given as a fixed-duration course, some patients may be able to keep the virus under control after stopping all hepatitis B treatment.¹

The label limits use to adults without cirrhosis who meet 3 conditions: they have taken HBV antiviral therapy for at least 6 months, they have suppressed HBV DNA, and they have hepatitis B surface antigen (HBsAg) levels of 3000 IU/mL or less on an FDA-authorized test.

The FDA also authorized the Roche Elecsys HBsAg II quant II RxDx assay as a companion diagnostic for patient selection and monitoring. Bepirovirsen received Fast Track, Breakthrough Therapy, and Priority Review designations.^1,2

"Taking patients off of continuous antiviral therapy and shifting them to a cure-based treatment is really going to impact the paradigm of care," said Mark Makhinson, PharmD, MBA, senior director of outpatient and specialty pharmacy at Mount Sinai Health System, in an interview with Pharmacy Times.

B-Well Trials Show Functional Cure in About 1 in 5 Patients

The approval rests on 2 replicate, double-blind phase 3 trials, B-Well 1 (NCT05630807) and B-Well 2 (NCT05630820). Both randomly assigned adults with noncirrhotic chronic HBV infection 2:1 to subcutaneous bepirovirsen 300 mg weekly or placebo for 24 weeks.

All patients were on stable nucleoside or nucleotide analogue (NA) therapy with HBsAg levels of more than 100 to 3000 IU/mL. Eligible patients stopped NA therapy at week 48. The primary outcome was functional cure at week 72, defined as HBsAg loss plus at least 24 weeks of HBV DNA below the lower limit of quantification.³

In B-Well 1, functional cure occurred in 127 of 650 patients (20%) receiving bepirovirsen vs none of 328 receiving placebo. In B-Well 2, it occurred in 106 of 570 (19%) versus none of 286. According to the FDA, 24% of patients receiving bepirovirsen across both trials met the requirements to stop their existing medicine, compared with none receiving placebo. GSK funded the trials.^1,3

Boxed Warning Puts Monitoring Front and Center

Bepirovirsen carries a boxed warning for serious liver reactions and low platelet counts, which can increase the risk of potentially life-threatening bleeding. Additional warnings cover worsening kidney function, serious inflammatory reactions such as vasculitis, and serious risks if the injection is not administered properly.

Patients need regular blood tests before and during treatment. The most common adverse effects, excluding laboratory abnormalities, are injection site reactions, fever, fatigue, and headache.¹

In a pooled 72-week analysis, adverse events occurred in 91% of patients receiving bepirovirsen versus 73% receiving placebo. Serious adverse events occurred in 7% versus 4%.

During treatment, grade 3 or higher events occurred in 16% vs 3%, and alanine aminotransferase (ALT) elevations were the most common grade 3 event with bepirovirsen (6%). Patients continue background antiviral therapy for at least 24 weeks after the last injection, so pharmacists can reinforce adherence, coordinate laboratory follow-up, and counsel on injection technique.^1,3

Formulary Calculus Shifts From Lifelong to Finite Therapy

Chronic hepatitis B can progress to cirrhosis and raise liver cancer risk. Health systems will therefore weigh a finite, monitored course against years of suppressive therapy and long-term disease complications.¹

"Even though the cost of treatment may be higher for this subset of patients, these improved outcomes and the reduced need for ongoing care and ongoing pharmaceutical care are valuable because the other effects of Hep B in the long term cost health systems money," Makhinson said. "By implementing a functional cure for these patients, you're avoiding the downstream effects and costs that these patients may incur."

Patient selection will shape that calculation. Only virally suppressed patients under the HBsAg threshold qualify. The companion diagnostic also adds a testing step that specialty pharmacy teams will need to build into prior authorization and referral workflows.^1,2

REFERENCES

1. FDA approves first-of-its-kind chronic hepatitis B treatment. News release. FDA. October 20, 2026. Accessed October 21, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-its-kind-chronic-hepatitis-b-treatment

2. GSK plc. Hibsago (bepirovirsen) approved in the US for the treatment of chronic hepatitis B (CHB). Form 6-K. US Securities and Exchange Commission. Accessed October 21, 2026. https://www.sec.gov/Archives/edgar/data/0001131399/000165495426009062/a7767z.htm

3. 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