GSK plc has announced positive results from two pivotal phase 3 clinical trials evaluating bepirovirsen, its investigational Antisense Oligonucleotide (ASO) therapy for the treatment of Chronic Hepatitis B (CHB). Findings from the B-Well 1 and B-Well 2 studies were simultaneously published in the New England Journal of Medicine and presented at the European Association for the Study of the Liver (EASL) Congress.

Pooled data from both trials demonstrated that six months of treatment with bepirovirsen achieved a statistically significant and clinically meaningful functional cure response rate of 19 percent in the overall study population, compared to no responses in the placebo group. The studies enrolled adult CHB patients with hepatitis B surface antigen (HBsAg) levels of 3,000 IU/ml or higher.

In a key secondary endpoint, patients with baseline HBsAg levels of 1,000 IU/ml or lower achieved a functional cure rate of 26 percent following treatment with bepirovirsen. This subgroup represents nearly 45 percent of diagnosed chronic hepatitis B cases globally. Current standard treatments for chronic hepatitis B generally require lifelong antiviral therapy and deliver functional cure rates in less than 1 percent of patients.

Functional cure is defined as the sustained absence of hepatitis B virus DNA and hepatitis B surface antigen in the blood for at least six months after stopping all treatment, indicating that the immune system is able to control the disease without medication. Clinical evidence has shown that loss of HBsAg is associated with a significant reduction in liver cancer risk and overall mortality.

The studies also showed encouraging secondary outcomes. Nearly half of patients treated with bepirovirsen achieved low levels of quantitative HBsAg one year after treatment completion, a marker associated with stronger immune control and improved long-term outcomes. In addition, a substantial proportion of patients maintained undetectable HBV DNA levels 72 weeks after treatment discontinuation.

The trials demonstrated an acceptable safety and tolerability profile consistent with previous studies of bepirovirsen. The most frequently reported adverse events included injection site redness, localised pain and temporary elevations in liver enzyme levels.

Tony Wood, Chief Scientific Officer at GSK, said chronic hepatitis B remains a major global health burden affecting more than 240 million people worldwide and contributing to more than half of global liver cancer cases. He stated that bepirovirsen offers the possibility of significantly improving functional cure rates compared to current standard therapies while potentially reducing the risk of long-term liver complications.

Professor Jinlin Hou, Director of the Guangdong Institute of Hepatology and lead author of the New England Journal of Medicine publication, noted that existing chronic hepatitis B treatments place a significant burden on both patients and healthcare systems while rarely achieving functional cure. He added that the new data may represent an important advancement in disease management as treatment guidelines increasingly prioritise functional cure as a key objective.

Bepirovirsen is currently under priority review by the US Food and Drug Administration with both Fast Track and Breakthrough Therapy designations. Regulatory reviews are also ongoing in Europe, Japan and China, where the therapy has received accelerated review designations. GSK expects the first regulatory decisions in the third quarter of 2026 and has already initiated launch preparations.

The B-Well 1 and B-Well 2 studies were global multicentre, randomised, double-blind, placebo-controlled trials conducted across 29 countries. The studies evaluated the efficacy, safety and durability of functional cure in nucleos(t)ide analogue-treated adult patients with chronic hepatitis B.

Chronic hepatitis B is a viral infection that can progress to long-term liver disease, cirrhosis and liver cancer. The condition affects more than 240 million people globally, including approximately 75 million people in China and 1.7 million in the United States. The disease is responsible for nearly 1.1 million deaths annually.

Bepirovirsen is designed to inhibit the production of hepatitis B viral RNA, thereby reducing viral proteins and suppressing hepatitis B surface antigen levels in the blood. The therapy is intended to help restore immune control over the virus and improve the likelihood of a durable treatment response.

GSK licensed bepirovirsen from Ionis Pharmaceuticals and collaborated on its development. The company continues to expand its hepatology pipeline, focusing on chronic hepatitis B and other fibro-inflammatory liver diseases, including metabolic dysfunction-associated steatohepatitis (MASH) and alcohol-associated liver disease.