Japan's Ministry of Health, Labour and Welfare (MHLW) has approved Hibsago (bepirovirsen) for chronic hepatitis B (CHB) in adults who have received at least six months of prior nucleos(t)ide analogue (NA) therapy and meet pre-defined viral markers — marking the first global approval for the antisense oligonucleotide (ASO) and the first approval for a CHB therapy capable of achieving functional cure in patients. GSK licensed bepirovirsen from Ionis Pharmaceuticals and led its development.
The approval covers adult patients with baseline hepatitis B surface antigen (HBsAg) levels of 3,000 IU/ml or below and hepatitis B virus (HBV) DNA below 90 IU/ml at treatment initiation. Bepirovirsen is administered as a six-month subcutaneous injection course. The MHLW review was accelerated under Japan's SENKU designation, which is granted to innovative medicines addressing high unmet medical need. As an ASO, bepirovirsen targets HBV RNA to suppress production of viral proteins including HBsAg, with the goal of enabling immune-mediated control without ongoing antiviral therapy.
Approval was supported by pooled data from the Phase III B-Well 1 and B-Well 2 trials, global randomized, double-blind, placebo-controlled studies conducted across 29 countries in NA-treated adults with baseline HBsAg of 3,000 IU/ml or below. The primary endpoint was the proportion of participants achieving functional cure — defined as undetectable HBsAg and HBV DNA below the lower limit of quantification for at least 24 weeks after stopping all treatment. Pooled results showed a 19% functional cure rate with bepirovirsen (233 of 1,220 participants) versus 0% with placebo (p<0.001 in both trials); in the subgroup with baseline HBsAg of 1,000 IU/ml or below, the rate reached 26% (200 of 768). Current NA therapy typically achieves less than 1% functional cure, as noted by GSK.