The investigational antisense medicine bepirovirsen produced a study-defined “functional cure” in about one in five selected adults with chronic hepatitis B in two Phase 3 trials published in the New England Journal of Medicine.
Bepirovirsen is an antisense oligonucleotide. It is designed to bind to hepatitis B virus RNA, reducing production of viral proteins and viral replication while potentially helping the immune system regain control.
The B-Well 1 and B-Well 2 trials enrolled people already receiving nucleoside or nucleotide analogue therapy and with hepatitis B surface antigen levels of 3,000 IU/mL or lower. Participants received weekly bepirovirsen injections or placebo for 24 weeks alongside their existing antiviral medicine.
At week 72, functional cure was reported in 127 of 650 participants given bepirovirsen in B-Well 1 (20%) and 106 of 570 in B-Well 2 (19%), compared with none in the placebo groups.
In these studies, functional cure meant sustained loss of hepatitis B surface antigen with undetectable HBV DNA after treatment was stopped. It does not mean sterilising cure or elimination of every trace of hepatitis B genetic material from liver cells.
The result is clinically important because sustained surface-antigen loss after a finite course of treatment is uncommon with current long-term antiviral therapy. It is equally important that about 80%—the majority of treated participants—did not reach the functional-cure endpoint.
Adverse events were reported more often with bepirovirsen than placebo. Grade 3 or higher events during treatment occurred in 16% versus 3%, and raised alanine aminotransferase, a liver enzyme, was the most common grade 3 event with bepirovirsen. The trials excluded some groups, including people with cirrhosis, so the findings do not apply to everyone with chronic hepatitis B.
Bepirovirsen remains investigational and is not currently an approved hepatitis B treatment. Regulatory review and longer follow-up are needed to define durability, safety and which patients are most likely to benefit.