Bepirovirsen Achieves 19% Functional Cure in Chronic Hepatitis B

GSK has announced pivotal phase 3 data for bepirovirsen, an investigational antisense oligonucleotide (ASO), showing a statistically significant functional cure rate of 19% in adults with chronic hepatitis B (CHB).

Results were simultaneously published in the New England Journal of Medicine and presented at the European Association for the Study of the Liver (EASL) congress on May 28, 2026.

“Today’s standard of care for CHB imposes a heavy burden on patients and healthcare systems, and rarely delivers a functional cure. With recent guidelines now prioritising functional cure, these new data could represent an important advance,” Jinlin Hou, Director of Guangdong Institute of Hepatology, China, and lead author of the New England Journal of Medicine’s manuscript, said in a statement. “Combined with improved testing and diagnosis, this innovation has the potential to improve the lives of millions living with CHB.”

Existing nucleos(t)ide analogue (NA) therapy suppresses viral replication but requires lifelong administration, with functional cure achieved in < 1% of treated patients. Bepirovirsen's phase 3 readout positions it as a potential first-in-class finite-duration regimen capable of inducing durable, treatment-free disease control.

In April 2026, the US Food and Drug Administration accepted for Priority Review the New Drug Application (NDA) for the investigational antisense oligonucleotide (ASO) for the treatment of adults with CHB. The Agency simultaneously granted bepirovirsen Breakthrough Therapy designation and established a PDUFA target action date of October 26, 2026.

The NDA was supported by results from a pair of global phase 3 trials: B-Well 1 and B-Well 2. Both were multicenter, randomized, double-blind, placebo-controlled trials conducted across 29 countries. Enrolled participants were adults with CHB who were receiving nucleos(t)ide analogue (NA) therapy and had baseline hepatitis B surface antigen (HBsAg) levels of ≤3000 IU/mL.

Participants received 6 months of bepirovirsen plus standard of care or placebo plus standard of care, with the primary endpoint assessed at week 72 — 24 weeks after discontinuing all treatment.

In pooled data from both trials, 19% of bepirovirsen recipients achieved functional cure, defined as undetectable HBV DNA and undetectable HBsAg for ≥ 24 weeks after stopping all treatment (233 of 1220 vs 0 of 614 in the placebo group; P <.001 in both trials), meeting the primary confirmatory endpoint. Results were consistent across both individual trials: 20% in B-Well 1 and 19% in B-Well 2.

In a key ranked secondary endpoint, the functional cure rate rose to 26% among participants with baseline HBsAg of ≤ 1000 IU/mL (200 of 768 vs 0 of 393 in the placebo group; P <.001 in both trials). This lower-antigen subgroup represents approximately 45% of diagnosed CHB cases globally.

Sustained HBV DNA suppression to below the lower limit of quantification at week 72 was achieved in 23% of all bepirovirsen recipients (283 of 1220 vs 0 of 614 in the placebo group; P <.001 in both trials) and in 31% of those with baseline HBsAg of ≤ 1000 IU/mL (237 of 768 vs 0 of 393; P <.001 in both trials). In an exploratory analysis, 49% of bepirovirsen recipients reached a quantitative HBsAg level of ≤ 100 IU/mL one year after the end of treatment, a threshold associated in the medical literature with enhanced immune control and improved outcomes.

The clinical significance of HBsAg clearance extends to long-term liver outcomes. HBsAg loss has been associated with an 89% reduction in the risk of liver cancer and a 62% reduction in all-cause mortality in a separate retrospective cohort analysis.

The safety and tolerability profile in the B-Well trials was consistent with prior bepirovirsen studies. The three most frequently observed adverse events were injection site erythema, local pain, and transient elevation of a hepatic enzyme. GSK reported no new safety signals.¹

“CHB affects over 240 million people worldwide and accounts for over half of global liver cancer cases. For the first time, bepirovirsen offers the possibility of significantly better functional cure rates than the current standard of care, and the potential to reduce the risk of long-term liver complications, including cancer,” Tony Wood, Chief Scientific Officer, GSK, said in a statement. “This is a major step forward in our growing pipeline to treat liver disease to help transform outcomes for patients.”

References

1. GSK. Bepirovirsen achieves unprecedented functional cure rates with potential to redefine treatment for chronic hepatitis B. Published May 28, 2026. Accessed May 29, 2026. https://www.gsk.com/en-gb/media/press-releases/bepirovirsen-achieves-unprecedented-functional-cure-rates-with-potential-to-redefine-treatment-for-chronic-hepatitis-b/

2. Hou JL, Lim SG, Buti M, et al. Phase 3 results of bepirovirsen treatment for chronic hepatitis B virus infection. N Engl J Med. 2026. doi:10.1056/NEJMoa2515131

3. Drysdale M, et al. Association of hepatitis B surface antigen loss with long-term clinical outcomes among patients with chronic hepatitis B infection. Z Gastroenterol. 2025;63(08):e481. doi:10.1055/s-0045-1810830