GSK’s Hibsago (bepirovirsen) approved in Japan as first functional cure for chronic hepatitis B
- MHLW approved Hibsago (bepirovirsen) as a functional cure for adult CHB patients meeting HBsAg ≤3000 IU/ml and HBV DNA <90 IU/ml after ≥6 months on nucleos(t)ide analogue therapy.
- Pooled B‑Well phase III data: 19% functional cure (233/1,220) versus 0/614 placebo in patients with ≤3000 IU/ml HBsAg; 26% (200/768) in the ≤1000 IU/ml subgroup.
- Exploratory results: HBsAg reduced to ≤100 IU/ml in 49% overall (598/1,220) and 62% (476/768) in the ≤1000 IU/ml subgroup at week 72.
- Safety profile described as acceptable; most common adverse events were injection site erythema, local pain and transient liver enzyme rise.
Approval and indication
Japan’s Ministry of Health, Labour and Welfare approved Hibsago (bepirovirsen), an antisense oligonucleotide, as a functional cure for chronic hepatitis B in adults who received at least six months of nucleos(t)ide analogue therapy and whose HBs antigen is ≤3000 IU/ml with HBV DNA <90 IU/ml.
Clinical evidence
Pooled B‑Well phase III trials (randomised, double‑blind, placebo‑controlled, 29 countries) showed a 19% functional cure rate after six months of treatment in patients with baseline HBsAg ≤3000 IU/ml (233 of 1,220 vs 0 of 614 placebo; p<0.001). In the ≤1000 IU/ml subgroup the rate was 26% (200 of 768 vs 0 of 393; p<0.001). Functional cure is defined as HBsAg undetectable for at least 24 weeks after stopping all treatment. Exploratory analyses reported HBsAg ≤100 IU/ml in 49% overall and 62% in the ≤1000 IU/ml subgroup at week 72.
Safety
The trials reported an acceptable safety and tolerability profile consistent with prior studies; the most frequent adverse events were injection site erythema, local pain and temporary rises in a liver enzyme.
Context and next steps
Japan has nearly one million people living with chronic hepatitis B and around 4,000 related deaths annually. Approval was accelerated by SENKU designation. GSK is progressing regulatory submissions in multiple jurisdictions, with decisions including the US expected in the coming months.
Source: GSK