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Liver Lineup: Bepirovirsen and the Push Toward Functional Cure in Hepatitis B
Tatyana Kushner, MD, joins Kim Brown, MD, and Nancy Reau, MD, to unpack bepirovirsen's phase 3 data and its implications for HBV care.
Welcome back to Liver Lineup: Updates & Unfiltered Insights!
Hepatitis B has gone decades without a finite treatment option, but that may be about to change. On this episode of Liver Lineup, hosts Nancy Reau, MD, and Kimberly Brown, MD, are joined by Tatyana Kushner, MD, a hepatologist at Weill Cornell Medicine, to discuss bepirovirsen, an investigational antisense oligonucleotide from GSK and Ionis Pharmaceuticals that recently became the first agent to demonstrate functional cure as a phase 3 primary endpoint in chronic hepatitis B (CHB).
Bepirovirsen Phase 3 Data in Chronic Hepatitis B
The conversation centers on data from the B-Well 1 and B-Well 2 trials, presented at the European Association for the Study of the Liver (EASL) Congress and simultaneously published in the New England Journal of Medicine in May 2026. The 2 replicate, double-blind, placebo-controlled trials enrolled 1834 participants across 29 countries with non-cirrhotic CHB who were on stable nucleos(t)ide analogue (NA) therapy and had baseline HBV DNA below 90 IU/mL and HBsAg between 100 and 3000 IU/mL, randomized 2:1 to weekly subcutaneous bepirovirsen 300 mg or placebo alongside standard NA therapy for 24 weeks.
Functional cure at week 72 was achieved in 20% of bepirovirsen-treated patients versus none of the placebo recipients in B-Well 1, and 19% versus 0% in B-Well 2, with response rates climbing further in patients with lower baseline HBsAg — up to 28% among those with baseline HBsAg of 1000 IU/mL or less. Sustained HBV DNA suppression after NA discontinuation, a key secondary endpoint, was reported in 23% of bepirovirsen-treated patients in both studies.
HBsAg Quantification and Patient Selection for Bepirovirsen
Kushner frames HBsAg quantification as the practical starting point for clinicians. She notes that she has begun routinely checking quantitative surface antigen in her own CHB patients, a test she previously considered non-actionable, because it will likely determine eligibility if bepirovirsen is approved. She cites discussion at a Coalition for Hepatitis Elimination conference suggesting roughly 50% to 60% of patients may fall under the HBsAg 3000 IU/mL threshold, though she, Reau, and Brown all note their own clinical experience suggests a lower proportion, complicated by limited access to quantitative, rather than qualitative, assays at some institutions.
Much of the discussion also addresses what functional cure means relative to spontaneous HBsAg loss and continued NA therapy; the group converges on sustained off-treatment HBsAg loss as the accepted endpoint, given its association with reduced HCC and cirrhosis progression risk, while acknowledging open questions about durability beyond the trial window.
Bepirovirsen Dosing, Monitoring, and Safety Considerations
The panel works through practical rollout questions: the drug's weekly injection schedule and potential for at-home administration, and the intensive monitoring likely required in the first 12 weeks given signals for ALT elevation and renal effects. The group agrees cirrhotic and decompensated patients, who were not studied, are unlikely candidates.
Brown highlights a discontinuation rate around 3% in the trials as reassuring relative to older interferon-based regimens, while Kushner cautions that real-world tolerance of ALT flares may differ from the closely monitored trial setting.
What's Next for Bepirovirsen in Hepatitis B Care
The conversation closes on access and uptake — whether primary care practices managing large hepatitis B populations, particularly in Asian American communities, will be positioned to administer and monitor this therapy, or whether care will concentrate in specialized centers. All 3 agree that regardless of uptake, an approval would likely drive renewed attention to hepatitis B screening and treatment linkage, areas where diagnosis and treatment rates in the US remain low.
Bepirovirsen is not yet approved; the FDA has accepted the New Drug Application for priority review and set a PDUFA goal date of October 26, 2026.
References
Hou J, et al. Phase 3 results of bepirovirsen treatment for chronic hepatitis B virus infection. N Engl J Med. 2026;394. doi:10.1056/NEJMoa2515131
Lok A. A major step toward a cure for hepatitis B infection. N Engl J Med. 2026;394:2471-2472. doi:10.1056/NEJMe2605575
Brooks A. FDA Grants Bepirovirsen Breakthrough Therapy Designation, Priority Review for Chronic Hepatitis B. HCPLive. April 28, 2026. Accessed July 8, 2026. https://www.hcplive.com/view/fda-grants-bepirovirsen-breakthrough-therapy-designation-priority-review-for-chronic-hepatitis-b
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