Bepirovirsen (IONIS-HBVRx/GSK3228836): An Investigational Antisense Oligonucleotide Therapy for Chronic Hepatitis B

Executive Summary

Bepirovirsen (also known as IONIS-HBVRx and GSK3228836) is an investigational antisense oligonucleotide (ASO) therapy representing a potentially transformative approach for the treatment of chronic hepatitis B (CHB). Developed by Ionis Pharmaceuticals and licensed to GSK for late-stage development, bepirovirsen is distinguished by a unique triple-action mechanism that combines direct antiviral activity with immune stimulation. It is designed to degrade all hepatitis B virus (HBV) RNA transcripts, thereby suppressing viral replication and the production of viral proteins, most notably the hepatitis B surface antigen (HBsAg), which is central to the virus's ability to evade the host immune system. Concurrently, bepirovirsen functions as an agonist of Toll-like receptor 8 (TLR8), stimulating innate immune responses. This dual-pronged attack on the virus—reducing its immunosuppressive shield while simultaneously boosting the host's immune response—positions bepirovirsen as a leading candidate in the global pursuit of a "functional cure" for CHB.