Hepatitis B Functional Cure Persists Off Treatment After Bepirovirsen

A hepatitis B functional cure achieved with 24 weeks of bepirovirsen (Hibsago; GSK) was maintained by about 9 in 10 responders through 48 weeks after stopping all hepatitis B virus (HBV) treatment, according to end-of-study results from the phase 3 B-Well 1 and 2 trials presented at The Liver Meeting 2026.¹ Two other presentations at the meeting modeled response in patients with lower antigen levels and laid out a US care pathway for delivering finite therapy.^2,3

The data arrive weeks after the FDA approved bepirovirsen on October 20, 2026, as the first antisense oligonucleotide for chronic HBV infection.⁴ It is indicated in combination with nucleos(t)ide analogue (NA) therapy for adults without cirrhosis who have received NA therapy for at least 6 months, have suppressed HBV DNA, and have hepatitis B surface antigen (HBsAg) levels of 3000 IU/mL or less as determined by an FDA-authorized test.⁴

About 1.7 million people in the United States live with chronic HBV, according to GSK.⁴ Standard NA therapy suppresses the virus but is typically taken indefinitely. Functional cure, defined in the B-Well trials as at least 24 weeks of sustained undetectable HBV DNA and HBsAg loss after finite therapy, is described by the investigators as the treatment goal in chronic HBV.¹ “Current care pathways for chronic hepatitis B (CHB) relying on long-term viral suppression deliver minimal functional cure (FC) rates,” wrote the authors of the US care pathway.³

B-Well End-of-Study Results Show Durable Functional Cure

B-Well 1 (NCT05630807) and B-Well 2 (NCT05630820) were global, double-blind trials in adults without cirrhosis whose HBV was suppressed on NA therapy and whose HBsAg was above 100 IU/mL and at or below 3000 IU/mL.¹ Patients were randomly assigned 2:1 to bepirovirsen 300 mg or placebo weekly for 24 weeks, and eligible patients discontinued NAs at week 48. The primary outcome was functional cure at week 72. The pivotal results were previously presented at the European Association for the Study of the Liver Congress 2026 and published in the New England Journal of Medicine.⁵

At week 72, 20% (127 of 650) of patients receiving bepirovirsen in B-Well 1 and 19% (106 of 570) in B-Well 2 achieved functional cure, compared with no patients receiving placebo.¹ About 24% of patients receiving bepirovirsen entered the durability stage after week 72. Among patients who stopped NAs, achieved functional cure at week 72, and completed week 96, 90% (114 of 127) in B-Well 1 and 92% (97 of 105) in B-Well 2 had a durable response, and similar durability was seen among those with baseline HBsAg of 1000 IU/mL or less. One patient who stopped NAs had a viral relapse and restarted NA therapy after week 72.

From weeks 73 to 96, the most common adverse events (AEs) were upper respiratory tract infection (4%), decreased creatinine renal clearance (2%), and nasopharyngitis (2%). Treatment-related AEs in that period occurred in 2% of patients and were single events. The investigators said bepirovirsen “had an acceptable safety profile without any evidence of latent safety concerns associated with prior [bepirovirsen] treatment.”

Modeling Response in Patients With Low HBsAg

Because the B-Well trials did not enroll patients with HBsAg below 100 IU/mL, GSK investigators used model-based extrapolation from 1194 B-Well participants benchmarked against 2067 patients in the real-world Everest study of pegylated interferon to estimate response in that group.² Functional cure rates in B-Well rose as baseline HBsAg fell, reaching 40% in the 100 to 200 IU/mL subgroup.

The final model predicted mean functional cure rates of approximately 46% to 53% with 24 weeks of bepirovirsen in NA-treated patients with baseline HBsAg below 100 IU/mL, with the lower bound of the model’s 95% CI suggesting at least a 34% rate of functional cure in this patient population.

Notably, the low-HBsAg estimates are model predictions, not trial results, and were produced by GSK, the drug’s manufacturer.

An 8-Step US Care Pathway for Finite HBV Therapy

A multidisciplinary panel of US clinicians, pharmacists, and advocates used a nominal group technique across 2 consensus meetings in 2026 to adapt a 9-step global care pathway proposed in 2025.³ The first meeting, mainly of nonspecialists, produced a 6-step pathway, and the second, mainly of specialists, expanded it to 8 steps, each with 100% consensus.

The final pathway separates shared decision-making at the start and end of treatment and adds detail to monitoring. Panelists identified quantitative HBsAg testing, access to functional cure treatment, patient engagement and adherence tools, provider education, care coordinators, and community awareness as priorities for implementation.

“The new 8-step US FC pathway and implementation priorities may help guide the paradigm shift in CHB management from chronic viral suppression to finite FC therapy,” the authors concluded.³

References

1. Hou J, Yuen MF, Lim SG, et al. Rates of functional cure in participants with chronic hepatitis B virus (HBV) infection treated with bepirovirsen: B-Well phase 3 trials end of study results. Paper presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, Colorado. Abstract 0266.

2. Whittaker D, Desikan R, Renardy M, Paff M, Theodore D, Nader A. Predicting functional cure response with bepirovirsen in patients with baseline HBsAg levels < 100 IU/mL. Late-breaking abstract presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, Colorado. Abstract 5024.

3. Ahn J, Caracostis A, Choi C, et al. New clinical care pathway in era of HBV functional cure: a US multidisciplinary expert consensus. Poster presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, Colorado. Abstract 4144.

4. Hibsago (bepirovirsen) approved in the US for the treatment of chronic hepatitis B (CHB). News release. GSK. October 20, 2026. Accessed November 6, 2026. https://www.gsk.com/media/alvmln3q/final-2-_bepi_us_approval_sea_201026.pdf

5. Steinzor P. Bepirovirsen achieves clinically meaningful functional cure rates in chronic hepatitis B. AJMC^®. May 28, 2026. Accessed November 6, 2026. https://www.ajmc.com/view/bepirovirsen-achieves-clinically-meaningful-functional-cure-rates-in-chronic-hepatitis-b