Ionis Pharmaceuticals Inc. partner GSK plc announced positive results from two pivotal Phase 3 studies, B-Well 1 and B-Well 2, evaluating the safety and efficacy of bepirovirsen, an investigational antisense oligonucleotide (ASO) for the treatment of chronic hepatitis B (CHB). The studies included over 1,800 patients from 29 countries. GSK licensed bepirovirsen from Ionis and the two companies have collaborated on its development.
CHB is a major health challenge affecting over 250 million people worldwide and is the leading cause of liver cancer. The current standard of care, nucelos(t)ide analogues, often requires lifelong therapy and the functional cure rates remain low, typically only 1%. Functional cure for CHB is when the virus can no longer be detected in the blood as measured by the sustained loss of hepatitis B surface antigen (HBsAg), a viral protein that signals ongoing infection, and undetectable hepatitis B virus DNA for at least 24 weeks after a finite course of treatment.
Functional cure is associated with significant reduction in the risk of long-term liver complications, including liver cancer, as well as all-cause mortality. The B-Well studies met their primary endpoint, and bepirovirsen demonstrated a statistically significant and clinically meaningful functional cure rate. Functional cure rates were 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 baseline surface antigen (HBsAg) =1000 IU/ml where an even greater effect was demonstrated. The studies demonstrated an acceptable safety and tolerability profile consistent with what was reported in other studies. 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.
If approved, bepirovirsen has The potential to become the first finite, six-month therapeutic option for CHB and to serve as a backbone for future sequential treatment strategies. Bepirovirsen has been recognized by global regulatory authorities for its innovation and potential to address significant unmet need in hepatitis B with Fast Track designation from the US FDA, Breakthrough Therapy designation in China and SENKU designation in Japan. GSK licensed bepirvirsen from Ionis in 2019 under a collaborative development and licensing agreement.
Under the terms of the agreement, Ionis received an upfront payment, license fee and development milestone payments and is eligible to receive an additional $150 million in regulatory and sales milestone payments as well as tiered royalties of 10-12% on net sales of bepirovirsen. B-Well 1 (NCT05630807) and B-Well 2 (NCT05630820) trials are global multi-center, randomized, 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 chronic hepatitis B and baseline surface antigen (NA)-treated participants with Chronic hepatitis B and baseline surface antigen ("CHB") 3000 IU/ml.
The primary endpoint assessed the proportion of participants achieving functional cure in patients with baseline surface antigen (HBsAg) 3000 IU/ml. A key secondary endpoint evaluated functional cure in participants with baseline HBsAg 1000 IU/ml. Functional cure is defined as hepatitis B surface antigen (HBsAg) loss and undetectable HBV DNA for at least 24 weeks after a finite course of treatment.
