Bepirovirsen in Hepatitis B: Who May Qualify, 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 cleared 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, how the drug differs from current therapy, and which patients may be candidates in an interview with HCPLive.

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

“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.² They were randomized 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 Among patients with baseline HBsAg ≤1000 IU/mL, a key secondary endpoint, the rates were 25% and 28%.²

How Bepirovirsen Differs From Nucleos(t)ide Analog Therapy

Bepirovirsen is an antisense oligonucleotide designed to block HBV messenger RNA.² According to Terrault, the drug acts within hepatocytes to reduce production of the viral proteins, including HBsAg, that the virus needs to make new virions. NA therapy acts on HBV DNA replication.

Terrault described the two mechanisms as complementary. She said HBsAg levels may fall sharply early in treatment, often becoming undetectable while patients are still receiving the drug.

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 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 Roche Elecsys HBsAg II quant II RxDx assay was authorized alongside the drug as a companion diagnostic for patient selection and monitoring.¹

Terrault said clinicians will likely start by looking at 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 for bepirovirsen.

Editors’ Note: Disclosures for Norah Terrault include GSK, Genentech-Roche, Helio Health, Durect Corp, Eiger Pharmaceuticals, and ImmunoCore.

References

1. FDA approves first-of-its-kind chronic hepatitis B treatment. US Food and Drug Administration. Published October 20, 2026. Accessed October 29, 2026.

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 October 29, 2026.

4. Bepirovirsen achieves 19% functional cure in chronic hepatitis B. HCPLive. Published May 29, 2026. Accessed October 29, 2026.

5. Liver Lineup: bepirovirsen and the push toward functional cure in hepatitis B. HCPLive. Published July 9, 2026. Accessed October 29, 2026.