Bepirovirsen Patient Selection in Hepatitis B: The Role of HBsAg Testing, With Norah Terrault, MD, MPH

Clinicians treating chronic hepatitis B virus (HBV) infection now have a finite therapy aimed at functional cure. The US Food and Drug Administration (FDA) approved bepirovirsen (Hibsago) on October 20, 2026, as an add-on to existing antiviral therapy for selected adults without cirrhosis, making it the first antisense oligonucleotide approved for the disease.¹,³

Norah Terrault, MD, MPH, professor of medicine and chief of gastroenterology and liver diseases at the Keck School of Medicine of USC, and a coauthor of the phase 3 B-Well 1 and B-Well 2 trials, discussed the data behind the approval and how clinicians can identify candidates in an interview with HCPLive.

B-Well 1 and B-Well 2 Functional Cure Results With Bepirovirsen

“We really have never had a therapy that, with finite treatment, gives us this rate of S antigen loss or functional cure,” Terrault said. “We now, for the first time, can talk to patients about having the ability to do a finite amount of therapy and achieve functional cure.”

The replicate, double-blind, placebo-controlled trials enrolled adults with noncirrhotic chronic HBV infection on stable nucleos(t)ide analog (NA) therapy across 29 countries. Participants had HBV DNA <90 IU/mL and hepatitis B surface antigen (HBsAg) levels between 100 and 3000 IU/mL at baseline, and were randomized 2:1 to subcutaneous bepirovirsen 300 mg weekly or placebo for 24 weeks.²

Functional cure was defined as HBsAg loss plus HBV DNA below the lower limit of quantification, sustained for ≥24 weeks after stopping all HBV treatment.² At week 72, functional cure was achieved by 20% of bepirovirsen recipients in B-Well 1 (127 of 650) and 19% in B-Well 2 (106 of 570), compared with none receiving placebo.²,⁴ In the key secondary endpoint, among patients with baseline HBsAg ≤1000 IU/mL, the rates were 25% and 28%, respectively.²

During treatment, grade ≥3 adverse events occurred in 16% of bepirovirsen recipients vs 3% of placebo recipients, with ALT elevations the most common.² Bepirovirsen carries a boxed warning for serious liver reactions and thrombocytopenia.¹ Terrault discussed the drug’s platelet, ALT, and kidney monitoring requirements in a companion interview.⁵

Quantitative HBsAg Testing to Identify Bepirovirsen Candidates

“What we’re going to have to have clinicians do, because I don’t think they’ve been doing it routinely, is to measure that level of hepatitis B surface antigen,” Terrault said.

The indication covers adults without cirrhosis who have received HBV antiviral therapy for ≥6 months, have suppressed HBV, and have HBsAg ≤3000 IU/mL as measured by an FDA-authorized test.¹ The FDA authorized the Roche Elecsys HBsAg II quant II RxDx assay alongside the drug as a companion diagnostic for patient selection.¹ Patients continue their existing antiviral therapy for ≥24 weeks after the final bepirovirsen injection and may then stop treatment if they meet specified clinical and laboratory criteria.¹

Terrault said clinicians will likely begin with patients already on NA therapy. For patients not yet on treatment, she said one option is to start NA therapy and later assess whether they qualify. Under the label, that assessment would follow ≥6 months of antiviral therapy.¹

Editor’s Note: Terrault reports relevant disclosures with GSK.

References

1. FDA approves first-of-its-kind chronic hepatitis B treatment. US Food and Drug Administration. Published October 20, 2026. Accessed November 6, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-its-kind-chronic-hepatitis-b-treatment

2. 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

3. Campbell P. FDA approves bepirovirsen for chronic hepatitis B. HCPLive. Published October 20, 2026. Accessed November 6, 2026.

4. Brooks A. Bepirovirsen achieves 19% functional cure in chronic hepatitis B. HCPLive. Published May 29, 2026. Accessed November 6, 2026.

5. HBV functional cure with bepirovirsen: platelet, ALT, kidney monitoring. HCPLive. Published October 29, 2026. Accessed November 6, 2026.

6. Liver Lineup: bepirovirsen and the push toward functional cure in hepatitis B. HCPLive. Published July 9, 2026. Accessed November 6, 2026.