GSK Announces Bepirovirsen Trial Data, 19% Functional Cure Rate Achieved

Ionis Pharmaceuticals (IONS) partner GSK (GSK) announced data for bepirovirsen, an investigational antisense oligonucleotide for the treatment of chronic hepatitis B. Results from the two Phase 3 trials, B-Well 1 and B-Well 2, were simultaneously published in the New England Journal of Medicine and presented at the European Association for the Study of the Liver congress. GSK licensed bepirovirsen from Ionis and the two companies have collaborated on its development. Pooled data from both trials showed that six-month treatment with bepirovirsen achieved a statistically significant and clinically meaningful 19% functional cure response rate in the overall study population, meeting the primary endpoints. In a key secondary endpoint, a functional cure rate of 26% was achieved in participants with 1000 IU/ml HBsAg level, a group that represents approximately 45% of diagnosed CHB cases globally. The current standard of care typically requires lifelong therapy, with functional cure rates achieved in less than 1% of patients. Functional cure occurs when the hepatitis B virus DNA and HBsAg are undetectable in the blood for at least six months after stopping all treatment. This indicates the disease is being controlled by the immune system without medication. Notably, in an exploratory analysis, 49% of bepirovirsen recipients achieved a quantitative hepatitis B surface antigen of 100 IU/mL one year after the end of treatment. Medical literature has linked this level of low surface antigen with increased immune control and improved patient outcomes. Moreover, 23% of all bepirovirsen recipients and 31% of bepirovirsen recipients with baseline HBsAg of 1000 IU/mL % achieved a sustained DNA lower limit of quantification at week 72 after stopping all treatment at week 48. The trials showed an acceptable safety and tolerability profile consistent with other studies of bepirovirsen. The three most frequently observed adverse events were injection site erythema, local pain and temporary rise in the blood level of a liver enzyme. Bepirovirsen is currently under priority review by the FDA with both Breakthrough and Fast Track Designation. It is also under review by regulatory authorities in Europe, Japan with SENKU designation and China with Breakthrough Therapy and Priority Review designation. GSK anticipates the first regulatory decisions in Q3 2026 and launch preparations are underway. GSK licensed bepirovirsen from Ionis in 2019 under a collaborative development and licensing agreement. Under the terms of the agreement, Ionis has received an upfront payment, license fee and development and regulatory milestone payments and is eligible to receive additional regulatory and sales milestone payments as well as tiered royalties of 10%-12% on net sales of bepirovirsen.