Bepirovirsen Meets Primary End Point for Functional Cure Rate of Hepatitis B

GSK announces positive results for bepirovirsen, an investigational antisense oligonucleotide for the treatment of chronic hepatitis B (CHB), in 2 phase 3 trials, B-Well 1 (NCT05630807) and B-Well 2 (NCT05630820).¹

“Bepirovirsen has the potential to transform treatment goals for people living with CHB by achieving significant functional cure rates—a first for the disease. CHB affects more than 250 million people and leads to approximately 56% of liver cancer cases worldwide,” Tony Wood, chief scientific officer at GSK, said in a news release.¹ “Today’s result supports our plans to progress bepirovirsen as a treatment and also continue its development as a backbone in future sequential therapies.”

Both trials met their primary end points, demonstrating statistically significant and clinically meaningful functional cure rates. Additionally, the functional cure rates were significantly higher for the study drug with the standard of care compared with the standard of care alone. The safety and tolerability profile was consistent with previously reported data.¹

About The Trials

Both the B-Well 1 and 2 trials were used to confirm the efficacy, safety, and pharmacokinetic profiles of bepirovirsen for 24 weeks, including loading doses, compared with the placebo. There were 4 stages, which included a double-blind treatment period for 24 weeks, nucleos(t)ide analogue treatment for 24 weeks, a nucleos(t)ide analogue cessation stage or continuing nucleos(t)ide analogue for 24 weeks, and a durability of response follow-up for another 24 weeks for patients who stopped nucleos(t)ide analogue treatment at week 48.^2,3

Patients included had documentary CHB infection of 6 months or more prior to screening and currently were receiving stable nucleos(t)ide analogue therapy, had plasma or serum hepatitis B virus (HBV) surface antigen concentrations of greater than 100 IU/mL but no greater than 3000 IU/mL, and plasma or serum hepatitis B virus DNA concentrations that were adequately suppressed.^2,3

The primary outcome for both trials was the number of individuals achieving functional cure with a baseline hepatitis B virus surface antigen of 3000 IU/mL or less. Secondary end points included the number of individuals achieving functional cure with a baseline hepatitis B virus surface antigen of 1000 IU/mL or less and the number of patients achieving sustained suppression of HBV DNA with a baseline hepatitis B virus surface antigen of 3000 IU/mL or less and 1000 IU/mL or less.^2,3

Previous Data Supporting Bepirovirsen

In a phase 2b trial (NCT04449029) published in the New England Journal of Medicine, investigators found that bepirovirsen 300 mg per week for 24 weeks resulted in sustained hepatitis B virus surface antigen and HBV loss in 9% to 10% of patients with CHB.⁴

They also found that decreases in hepatitis B virus surface antigen and HBV DNA levels were dependent on the duration of the treatment, and for many patients, both levels increased following treatment discontinuation. As for safety, investigators noted that adverse events were more common in the study treatment groups compared to patients receiving the placebo. Injection-site reaction, pyrexia, fatigue, and increased alanine aminotransferase levels were reported more frequently with bepirovirsen than with the placebo.⁴

“Larger trials and longer follow-up are needed to assess the safety and efficacy of bepirovirsen,” the study authors concluded.⁴

READ MORE: Infectious Disease Resource Center

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REFERENCES

1. GSK announces positive results from B-Well 1 and B-Well 2 phase III trials for bepirovirsen, a potential first-in-class treatment for chronic hepatitis B. News release. GSK. January 7, 2026. Accessed January 7, 2026. https://www.gsk.com/en-gb/media/press-releases/gsk-announces-positive-results-from-b-well-1-and-b-well-2-phase-iii-trials-for-bepirovirsen-a-potential-first-in-class-treatment-for-chronic-hepatitis-b/

2. Study of bepirovirsen in nucleos(t)ide analogue-treated participants with chronic hepatitis B (B-Well 1) (B-Well 1). ClinicalTrials.gov identification: NCT05630807. Updated December 15, 2025. Accessed January 7, 2026. https://clinicaltrials.gov/study/NCT05630807

3. Study of bepirovirsen in nucleos(t)ide analogue-treated participants with chronic hepatitis B (B-Well 2) (B-Well 2). ClinicalTrials.gov identification: NCT05630820. Updated December 12, 2025. Accessed January 7, 2026. https://clinicaltrials.gov/study/NCT05630820

4. Yuen MF, Lim SG, Plesniak R, et al. Efficacy and Safety of Bepirovirsen in Chronic Hepatitis B Infection. N Engl J Med. 2022;387(21):1957-1968. doi:10.1056/NEJMoa2210027