Bepirovirsen (GSK3228836) in chronic hepatitis B infection: an evaluation of phase II progress

Chronic hepatitis B infection is a major global health issue associated with significant liver-related morbidity and mortality. While existing treatments can suppress the virus effectively, they are incapable of inducing functional cure, as defined by hepatitis B surface antigen (HBsAg) seroclearance. Currently, numerous novel compounds are being developed, including bepirovirsen, an antisense oligonucleotide (ASO).

This review summarizes the mechanism of action, pharmacokinetics, clinical efficacy and safety data collected from phase I and II studies of bepirovirsen. The data were extracted from publications relevant to the pivotal trials of bepirovirsen, in either full manuscript or conference abstracts.

Bepirovirsen, a 20-mer ASO, has already entered phase III clinical evaluation using the optimal dosing regimen of 300 mg subcutaneous injection weekly for 24 weeks in nucleoside analogue-treated HBeAg-negative non-cirrhotic patients with low (<3000 IU/mL) baseline HBsAg. The durability and long-term clinical outcomes among Bepirovirsen responders will need to be evaluated. The stop-to-cure approach in those reaching HBsAg < 100 IU/mL should also be explored. In the long run, Bepirovirsen has the potential to facilitate viral hepatitis elimination.