Bepirovirsen Functional Cure Durable Through Week 96 in Chronic Hepatitis B

Functional cure achieved with 24 weeks of bepirovirsen was durable in 91% of responders with chronic hepatitis B virus (HBV) infection through Week 96, 48 weeks after stopping all HBV treatment, according to end-of-study results from the phase 3 B-Well 1 and B-Well 2 trials presented at AASLD The Liver Meeting 2026.¹

Man-Fung Yuen, MD, PhD, of the University of Hong Kong, presented the data. The US Food and Drug Administration approved bepirovirsen (Hibsago) on October 20, 2026, as the first antisense oligonucleotide for chronic HBV infection, for use with nucleos(t)ide analog (NA) therapy in adults without cirrhosis and hepatitis B surface antigen (HBsAg) of 3000 IU/mL or less.³

How Durable Was Functional Cure With Bepirovirsen?

B-Well 1 and B-Well 2 randomized noncirrhotic adults with NA-suppressed chronic HBV infection (HBV DNA <90 IU/mL) and HBsAg above 100 to 3000 IU/mL to bepirovirsen 300 mg or placebo weekly for 24 weeks.¹,² Eligible participants discontinued NAs at Week 48. Functional cure was defined as HBV DNA below the lower limit of quantification (LLOQ) and HBsAg loss sustained for at least 24 weeks off all therapy.¹

At Week 72, 19% (233/1220) of bepirovirsen recipients achieved functional cure, compared with none of 614 placebo recipients.¹,² Among those with baseline HBsAg of 1000 IU/mL or less, the rate was 26% (200/768) vs 0% (0/393). A total of 291 bepirovirsen-treated participants who stopped NAs entered the durability stage after Week 72.¹

Among responders who stopped NAs and completed Week 96, durable functional cure occurred in 90% (114/127) in B-Well 1 and 92% (97/105) in B-Well 2, for a pooled rate of 91%.¹ Durability was similar among participants with baseline HBsAg of 1000 IU/mL or less. HBV DNA suppression off all treatment was maintained through Week 96 in 96% of participants with HBV DNA below LLOQ at Week 72.¹

How Did Baseline HBsAg Affect Functional Cure Rates?

In a post hoc pooled analysis, functional cure rates declined as baseline HBsAg increased.¹ Rates at Weeks 72 and 96 were 40% and 35% among participants with baseline HBsAg below 200 IU/mL, 31% and 30% with 200 to less than 300 IU/mL, and 16% and 15% with 500 to less than 1000 IU/mL. Among those with baseline HBsAg of 2500 to 3000 IU/mL, rates were 4% at both timepoints.¹

Beyond functional cure, 49% of bepirovirsen recipients either achieved functional cure or had quantitative HBsAg of 100 IU/mL or less at Week 72.¹ In a post hoc analysis of participants with available Week 96 data, 97% had HBsAg of 100 IU/mL or less.

Among participants who stopped NAs, 5 had HBV DNA replication at Week 72, and 1 had viral relapse and reinitiated NAs.¹ During Weeks 73 to 96, the most common adverse events were upper respiratory tract infection (4%; 12/291), decreased creatinine renal clearance (2%; 5/291), and nasopharyngitis (2%; 5/291). Treatment-related adverse events after bepirovirsen cessation occurred in 2% (5/291) of participants and were single events.¹

In a recent interview with HCPLive, Norah Terrault, MD, MPH, a B-Well coauthor, discussed which patients may be candidates for bepirovirsen, with quantitative HBsAg testing central to selection.⁴

References:

1. Hou J, Yuen MF, Lim SG, et al. Rates of functional cure in participants with chronic hepatitis B virus infection treated with bepirovirsen: B-Well phase 3 trials end of study results. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO.

2. Hou J, Lim SG, Buti M, et al. 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 7, 2026. https://www.hcplive.com/view/fda-approves-bepirovirsen-for-chronic-hepatitis-b

4. Terrault N. Bepirovirsen in hepatitis B: who may qualify, with Norah Terrault, MD, MPH. HCPLive. Published October 29, 2026. Accessed November 7, 2026. https://www.hcplive.com/view/bepirovirsen-in-hepatitis-b-who-may-qualify-with-norah-terrault-md-mph