Bepirovirsen Meets Function Cure Endpoint in Phase 3 B-Well Trials for Hepatitis B

GSK has announced positive results from a pair of phase 3 trials, B-Well 1 and B-Well 2, evaluating bepirovirsen, an investigational antisense oligonucleotide, for the treatment of chronic hepatitis B (CHB) in > 1800 patients from 29 countries.1

As described in the January 7, 2026, press release from the Company, the B-Well trials met their primary endpoint and bepirovirsen demonstrated a statistically significant and clinically meaningful functional cure rate. Of note, results were statistically significant across all ranked endpoints, including in patients with baseline surface antigen (HBsAg) <=1000 IU/ml where an even greater effect was demonstrated.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,” Tony Wood, Chief Scientific Officer at GSK, said in a statement.1 “CHB affects more than 250 million people and leads to approximately 56% of liver cancer cases worldwide. 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 to transform outcomes in liver disease.”

Bepirovirsen is a triple action investigational antisense oligonucleotide, designed to recognise and orchestrate the destruction of the genetic components of the hepatitis B virus that can lead to chronic disease, potentially allowing a person’s immune system to regain control. It inhibits the replication of viral DNA in the body, suppresses the level of HBsAg in the blood, and stimulates the immune system to increase the chances of a durable and sustained response.1

GSK licensed bepirovirsen from Ionis Pharmaceuticals in 2019 under a collaborative development and licensing agreement.1,2

The B-Well 1 and B-Well 2 trials are global multi-centre, randomised, double-blind, placebo-controlled trials conducted in 29 countries. They assessed the efficacy, safety, pharmacokinetic profile, and the durability of functional cure in nucleos(t)ide analogue (NA)-treated participants with CHB and HBsAg ≤3000 IU/ml.1

The primary endpoint assessed the proportion of participants achieving functional cure in patients with HBsAg ≤3000 IU/ml. A key ranked secondary endpoint evaluated functional cure in participants with baseline HBsAg ≤1000 IU/ml, defined as HBsAg loss and undetectable HBV DNA for > 24 weeks after a finite course of treatment.1

Results showed bepirovirsen demonstrated a statistically significant and clinically meaningful functional cure rate, which was significantly higher with bepirovirsen plus standard of care compared with standard of care alone. Results were statistically significant across all ranked endpoints, including in patients with HBsAg <=1000 IU/ml where an even greater effect was demonstrated. The trials demonstrated an acceptable safety and tolerability profile consistent with what was reported in other studies.1

As described in the release from GSK, full results will be submitted for presentation at an upcoming scientific congress, published in a peer-reviewed journal and used to support regulatory submissions to health authorities worldwide.1

“CHB is one of the most common, persistent viral infections in the world, with currently no approved therapy that can achieve meaningful functional cure. Bepirovirsen is uniquely positioned to effectively treat CHB based on its potential to reduce the replication of hepatitis B virus, suppress hepatitis B surface antigen and stimulate the immune system,” said Brett Monia, PhD, chief executive officer, Ionis.2 “Today’s positive results are made possible by the strategic collaboration between Ionis and GSK, and demonstrate that bepirovirsen has the potential to bring hope to the millions of people living with CHB. This is the first of five anticipated Phase 3 readouts from Ionis’ partnered programs this year, underscoring the broad applicability of our technology.”

References

1. GSK. 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. 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. Ionis Pharmaceuticals. Ionis partner GSK announces positive topline results from B-Well 1 and B-Well 2 Phase 3 studies for bepirovirsen, a potential first-in-class medicine for chronic hepatitis B. January 7, 2026. Accessed January 7, 2026. https://www.businesswire.com/news/home/20260106121974/en/Ionis-partner-GSK-announces-positive-topline-results-from-B-Well-1-and-B-Well-2-Phase-3-studies-for-bepirovirsen-a-potential-first-in-class-medicine-for-chronic-hepatitis-B