Evidence of durable response to bepirovirsen in B-Clear On-NA responders: B-Sure second report

초록

Introduction Bepirovirsen (BPV) is an unconjugated antisense oligonucleotide, for the treatment of chronic hepatitis B (HBV) infection. Data from a Phase 2b study (B-Clear) indicated that a subset of participants (pts) achieved a response at the end of treatment, sustained for 24 weeks. This occurred in pts on and not on nucleos(t)ide analog (NA) therapy. Pts who had a complete (CR) or partial (PR) response at the end of B-Clear were eligible for this long-term durability study (B-Sure). Aim Here, we present data on the durability of response for B-Clear On-NA CRs and PRs who entered B-Sure. Methods CR defined as hepatitis B surface antigen (HBsAg) <0.05 IU/mL and HBV DNA <lower limit of quantification (LLOQ), and PR as HBsAg <100 IU/mL and HBV DNA <LLOQ. If eligible, pts discontinued NA treatment 3 months into B-Sure and were followed to determine the durability of response off all HBV therapy. Adverse events were recorded. Results 11 CRs and 29 PRs entered B-Sure (Figure). In B-Clear, 77% of pts were HBeAg negative, 19/44 (43%, and 32/44 (73%) had HBsAg ≤1000 IU/mL. For CR pts, 9/11 (82%) discontinued NAs 3 months after rollover into B-Sure; 7/9 (78%) maintained a CR to 6 months post NA cessation, thus achieving functional cure (FC). For PR pts, 23 pts discontinued NAs 3 months after rollover into B-Sure. 8/23 of PR pts either maintained PR status (5/23) or had achieved and maintained a CR (3/23) 6 months post NA cessation (i.e. FC). None of the 9 CRs who discontinued NAs had restarted NA therapy by 9 months post NA cessation. Of the PRs who discontinued NAs, 8 had restarted NAs within 6 months post NA cessation due to virological breakthrough. Conclusions These data provide evidence of the durability of FC, particularly in CRs. Presented originally at The Liver Meeting - 74th Annual Meeting of the American Association for the Study of Liver Diseases, 10-14 November 2023.