Bepirovirsen Shows Breakthrough Potential for Functional Cure in Chronic Hepatitis B

In the pivotal phase 3 global, multi-center, randomized, double-blind, placebo-controlled B-Well 1 (NCT05630807) and B-Well 2 (NCT05630820), bepirovirsen (GSK) demonstrated a statistically significant and clinically meaningful functional cure rate for the treatment of chronic hepatitis B (CHB).^1-3

“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 from GSK, said in a news release.¹

What is CHB?

Hepatitis B is a serious liver infection caused by the hepatitis B virus (HBV). It can be acute and last less than 6 months or chronic and last longer, with chronic infection increasing the risk of liver failure, liver cancer, and cirrhosis.^1,4

For acute hepatitis B, symptoms can range from mild to severe and usually appear 1 to 14 months after infection, though they may occur as early as 2 weeks. Some individuals, especially young children, may not present symptoms, while others could experience abdominal pain, dark urine, fever, joint pain, loss of appetite, nausea and vomiting, extreme tiredness, and jaundice. CHB can go undetected for many years and may only be discovered when an individual becomes seriously ill from liver disease.⁴

The current standard treatment for CHB uses nucleos(t)ide analogues, which often require lifelong therapy and have low functional cure rates of about 1%. A functional cure rate means the virus is no longer detectable in the blood, shown by sustained loss of hepatitis B surface antigen and undetectable HBV DNA for at least 24 weeks after treatment ends.^1,4

Understanding the Role of Bepirovirsen for CHB

As a triple-action investigational antisense oligonucleotide (ASO), bepirovirsen targets and destroys HBV RNA, which aims to help the immune system regain control of the infection. It works by inhibiting viral DNA replication, lowering hepatitis B surface antigen levels in the blood, and stimulating the immune system to support a sustained response.¹

Bepirovirsen Advances Treatment for CHB in Phase 3 Trials

The B-Well trials evaluated the effectiveness, safety, pharmacokinetics, and durability of functional cure in nucleos(t)ide analogue-treated patients with CHB and baseline hepatitis B surface antigen (HBsAg) levels of 3000 IU/ml or less. The primary end point was to measure how many participants achieved a functional cure and undetectable HBV DNA for at least 24 weeks after treatment. The study authors noted that additional analysis was conducted in those with HBsAg levels of 1000 IU/ml or less.¹

Data from the B-Well trials demonstrated that both met their primary end point and displayed a statistically significant and clinically meaningful functional cure rate among individuals that were treated with bepirovirsen alone or in combination with standard of care, compared to standard of care alone.¹

The results were statistically significant across all key end points, with an even greater effect observed in patients with baseline HBsAg levels of 1000 IU/ml or less. The trials also showed acceptable safety and tolerability profiles that were consistent with previous studies.¹

In a previously conducted phase 2b trial (NCT04449029), published in the New England Journal of Medicine, researchers assessed weekly 300 mg doses of bepirovirsen for 24 weeks and found that they led to sustained HBsAg and HBV DNA loss in 9% to 10% of participants with CHB.^5,6

“Today’s result supports our plans to progress bepirovirsen as a treatment and also continue its development as a backbone in future sequential therapies. We’re pleased by this major advance in our expanding hepatology pipeline, aimed at transforming outcomes in liver disease,” Wood said.¹

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 8, 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 identifier: NCT05630807. Updated December 15, 2025. Accessed January 9, 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 identifier: NCT05630820. Updated December 12, 2025. Accessed January 8, 2026. https://clinicaltrials.gov/study/NCT05630820

4. Mayo Clinic Staff. Hepatitis B. News release. Mayo Clinic. December 9, 2025. Accessed January 8, 2026. https://www.mayoclinic.org/diseases-conditions/hepatitis-b/symptoms-causes/syc-20366802

5. Yuen M, Lim S, Plesniak R, et al. Efficacy and Safety of Bepirovirsen in Chronic Hepatitis B Infection. N Engl J Med 2022;387:1957-1968. doi:10.1056/NEJMoa2210027

6. A Study of GSK3228836 in Participants With Chronic Hepatitis B (CHB) (B-Clear). ClinicalTrials.gov identifier: NCT04449029. Updated May 16, 2023. Accessed January 8, 2026. https://clinicaltrials.gov/study/NCT04449029