GSK’s antisense oligonucleotide bepirovirsen achieved functional cure in pivotal Phase 3 chronic hepatitis B trials, with 19% of patients meeting the primary endpoint and regulatory decisions expected in Q3 2026.
Written By: Sanika Komwar, BDS
Reviewed By: Pharmacally Editorial Team
GSK reported positive pivotal Phase 3 results for bepirovirsen, its investigational antisense oligonucleotide (ASO) therapy for chronic hepatitis B (CHB), demonstrating clinically meaningful functional cure rates after finite treatment. Findings from the B-Well 1 (NCT05630807) and B-Well 2 (NCT05630820) trials were presented at the EASL Congress 2026 and published in the New England Journal of Medicine.
Primary Endpoint Met
Pooled data from the two global studies showed that 19% of patients treated with bepirovirsen achieved functional cure at Week 72, compared with 0% in the placebo arm. Functional cure was defined as sustained loss of detectable hepatitis B surface antigen (HBsAg) and HBV DNA after stopping therapy, assessed 24 weeks post-treatment. Among patients with baseline HBsAg ≤1000 IU/mL, cure rates increased to 26%, identifying a subgroup with stronger response potential.
Exploratory Outcomes
Nearly half of treated patients achieved quantitative HBsAg ≤100 IU/mL at follow-up, a threshold associated with improved long-term immune control. In addition, 23% of participants achieved sustained suppression of HBV DNA below the lower limit of quantification at Week 72.
Clinical Context
Chronic HBV affects more than 240 million people worldwide and remains a major driver of cirrhosis and hepatocellular carcinoma. Current nucleos(t)ide analogue therapies suppress HBV replication but rarely eliminate surface antigen, leaving most patients on lifelong treatment. Updated international guidelines now recognize functional cure as a central therapeutic goal, given its association with substantially lower risks of liver cancer and mortality.
Mechanism and Safety
Bepirovirsen is an ASO that targets HBV RNA, reducing production of viral proteins and surface antigen while supporting restoration of immune control. Safety findings were consistent with earlier studies, with the most common adverse events being injection-site erythema, injection-site pain, and transient liver enzyme elevations.
Expert and Regulatory Outlook
Tony Wood, GSK’s Chief Scientific Officer, said the data mark “a major advance in efforts to improve long-term outcomes for patients living with chronic hepatitis B, particularly given the disease’s strong association with liver cancer.”
Lead investigator Professor Jinlin Hou added that functional cure offers a path beyond the substantial burden of lifelong therapy.
Bepirovirsen is under Priority Review by the U.S. FDA, with Breakthrough Therapy and Fast Track designations. Regulatory reviews are also ongoing in Europe, Japan, and China, with first regulatory decisions expected in Q3 2026. GSK has begun launch preparations, including a commercialization collaboration with Sino Biopharmaceutical in China.
Reference
About the Writer
Sanika Santosh Komawar (LinkedIn) is a healthcare writer and third-year BDS student at KBH Dental College under Maharashtra University of Health Sciences, with a strong interest in dentistry, healthcare communication, and continuous learning. She has participated in various conference poster presentations and has developed effective communication and leadership skills through her academic and extracurricular activities.