GSK reports positive Phase III B-Well 1 and B-Well 2 trial results for bepirovirsen, showing clinically meaningful functional cure rates and supporting its potential as a first-in-class treatment for chronic hepatitis B.
Written By: Pharmacally Medical News Desk
GlaxoSmithKline (GSK) announced positive results from its pivotal phase III trials, B-Well 1 and B-Well 2, evaluating bepirovirsen, an investigational antisense oligonucleotide designed to treat chronic hepatitis B (CHB) and potentially achieve functional cure. The company said both studies met their primary endpoints and demonstrated statistically significant and clinically meaningful improvements in functional cure rates compared with standard of care alone.
Topline Results and Functional Cure Outcomes
In the global, multi-center, randomized, double-blind, placebo-controlled B-Well 1 [NCT05630807] and B-Well 2 trials [NCT 05630820], bepirovirsen met its primary endpoint, showing that patients receiving the investigational therapy achieved higher functional cure rates than those on standard nucleos(t)ide analogue therapy alone. The effect was statistically significant across ranked endpoints, including an even greater benefit in patients with lower baseline hepatitis B surface antigen (HBsAg) levels (<=1000 IU/m).
Functional cure in hepatitis B is defined as sustained loss of HBsAg and undetectable hepatitis B virus DNA for at least 24 weeks after a finite course of treatment. This outcome, if achieved, indicates that patients can maintain viral control without ongoing antiviral drugs, a major shift from the current lifelong suppression approach.
Investigational Drug Profile: Bepirovirsen’s Mechanism and Potential
Bepirovirsen is a triple-action antisense oligonucleotide licensed by GSK from Ionis Pharmaceuticals. It is designed to target hepatitis B virus RNA, inhibiting viral replication, reducing surface antigen levels, and stimulating the immune response to improve sustained control of the infection.
The trials enrolled more than 1,800 adults with CHB across 29 countries, including participants on existing standard of care therapy. Besides efficacy, bepirovirsen showed an acceptable safety and tolerability profile consistent with prior studies.
Comments From GSK and Clinical Significance
Tony Wood, Chief Scientific Officer at GSK, highlighted the potential for bepirovirsen to “transform treatment goals for people living with CHB by achieving significant functional cure rates,” noting the global burden of chronic hepatitis B and the limitations of current therapies.
Chronic hepatitis B affects more than 250 million people worldwide and is a leading cause of liver cancer almost 56% and liver-related mortality. Most existing treatments suppress viral replication but rarely lead to a functional cure, leaving a significant unmet need in patient care.
Next Steps: Presentation and Regulatory Filings
GSK plans to submit the full dataset for presentation at an upcoming scientific congress and for publication in a peer-reviewed journal. Based on these pivotal results, the company intends to pursue regulatory filings in key markets starting in the first quarter of 2026.
If approved, bepirovirsen could become the first finite course therapy with the potential to achieve functional cure in CHB, offering a meaningful change in disease management and long-term outcomes for millions of patients.
Background: Chronic Hepatitis B and Treatment Landscape
Hepatitis B virus infection can lead to chronic liver inflammation, cirrhosis, and hepatocellular carcinoma if not controlled. Standard therapy with nucleos(t)ide analogues effectively suppresses viral replication but rarely leads to functional cure. A therapy that reliably achieves sustained antigen loss and undetectable viral DNA after a defined treatment course could reduce the need for lifelong therapy and lower the risk of liver complications.
This result places bepirovirsen among the most advanced investigational treatments for CHB and a potential new standard if regulatory agencies grant approval based on the B-Well data.
References
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, 07 January 2026, 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 | GSK
Study of Bepirovirsen in Nucleos(t)Ide Analogue-treated Participants with Chronic Hepatitis B (B-Well 1) (B-Well 1), ClinicalTrials.gov ID NCT05630807, https://clinicaltrials.gov/study/NCT05630807
Study of Bepirovirsen in Nucleos(t)Ide Analogue-treated Participants with Chronic Hepatitis B (B-Well 2) (B-Well 2), ClinicalTrials.gov ID NCT05630820, https://clinicaltrials.gov/study/NCT05630820