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HBsAg testing becomes central to selecting patients for bepirovirsen, a finite hepatitis B therapy given alongside NA treatment.
For patients with chronic hepatitis B virus (HBV) infection, functional cure with bepirovirsen (Hibsago) follows a stretch of intensive laboratory monitoring. The US Food and Drug Administration (FDA) approved the antisense oligonucleotide on October 20, 2026, with a boxed warning for on-treatment hepatic flares and thrombocytopenia.¹,²
In an interview with HCPLive, 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 B-Well trials, explained what functional cure may mean for patients, how clinicians can prepare for the monitoring burden, and which questions about the therapy remain open.
“They’re no longer infected, and that really means a lot for a patient,” Terrault said. “They don’t have to worry about potentially transmitting to others. They don’t have to carry the stigma of being infected.”
In the phase 3 B-Well 1 and B-Well 2 trials, functional cure was defined as HBV DNA below the lower limit of quantification with hepatitis B surface antigen (HBsAg) loss, sustained for ≥24 weeks off all HBV treatment. It was achieved by 20% and 19% of bepirovirsen recipients, compared with none receiving placebo.³,⁴
Terrault said functional cure is the clinical state in which the risk of liver cancer, cirrhosis, and liver failure is lowest. She noted that patients who have had the disease for decades may already have liver damage and may retain some risk. She added that functional cure may also mean less monitoring and no need for lifelong nucleos(t)ide analog (NA) therapy.
“Physicians need to be aware of that and have in place a system to ensure that the monitoring is being completed,” Terrault said. “It’s intense for a period of time, and then ultimately, hopefully, no monitoring required if you achieve functional cure.”
According to the prescribing information, ALT and total bilirubin should be checked before treatment and frequently during it. Treatment may need to be interrupted, dose reduced, or stopped based on liver laboratory results.⁵ Bepirovirsen is contraindicated in patients with a platelet count <100 × 10⁹/L, and platelet counts should be monitored weekly during treatment.⁵ The label also carries warnings for worsening kidney function and serious inflammatory reactions such as vasculitis.¹
Terrault said ALT flares may occur as HBsAg declines and are generally well tolerated, but they require close follow-up. By comparison, she noted that patients on stable NA therapy are often tested only every 6 months.
Ahead of the approval, Tatyana Kushner, MD, of Weill Cornell Medicine, joined Liver Lineup hosts Nancy Reau, MD, and Kimberly Brown, MD, to discuss the B-Well data and what bepirovirsen rollout could look like in practice, including ALT and renal monitoring.⁶
Listen to the full episode
Terrault said the next questions include whether bepirovirsen could be paired with other agents in the HBV pipeline. Another is whether patients who don’t reach functional cure, but finish treatment with lower HBsAg levels, could benefit from a second course. She noted that retreatment has not yet been studied.
In exploratory analyses, bepirovirsen lowered HBsAg to ≤100 IU/mL in 49% of the overall study population and in 62% of patients with baseline HBsAg ≤1000 IU/mL as of week 72.⁵ Terrault said longer-term studies are needed to understand what that lower level means for patients who did not reach functional cure, and that this group may be well suited to retreatment.
She also encouraged clinicians to begin measuring HBsAg periodically in patients on NA therapy, and to start conversations with patients about functional cure and the monitoring commitment it requires.
Editors’ Note: Disclosures for Norah Terrault include GSK, Genentech-Roche, Helio Health, Durect Corp, Eiger Pharmaceuticals, and ImmunoCore.
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