Bepirovirsen is an investigational antisense oligonucleotide (ASO) therapy being developed for chronic hepatitis B. It targets all HBV messenger RNAs through a triple-action mechanism: (1) by reducing HBV replication, (2) by suppressing hepatitis B surface antigen (HBsAg) levels, and (3) by stimulating the immune system to potentially achieve a functional cure.

​In the Phase IIb B-Clear trial, approximately 10% of participants achieved sustained HBsAg and HBV DNA loss after 24 weeks of treatment. Efficacy was observed in both nucleos(t)ide analogue (NA)-treated and untreated patients. The ongoing Phase III B-Well program aims to further evaluate bepirovirsen’s potential, focusing on patients with HBsAg ≤3,000 IU/mL. HBV cure occurs rarely with monotherapy, and combination therapies are being evaluated. Cure rates are significantly higher in persons with lower HBsAg levels. The FDA has recognized bepirovirsen with fast-track designation, highlighting its status as the only single agent in Phase III showing promise for finite-duration therapy for HBV, with the possibility of functional cure in some patients. This represents a potential breakthrough in chronic viral hepatitis B treatment.

​GSK in-licensed bepirovirsen from Ionis (formerly Isis) Pharmaceuticals in 2019. Ionis holds the primary patent on bepirovirsen, which has been filed in many low- and middle-income countries (LMICs) and is expected to expire in 2032.​