Up to 24 months durability of functional cure in response to bepirovirsen plus Peg-IFN sequential therapy in B-Together responders: results from the B-Sure study

초록

Background and aims: Bepirovirsen (BPV) is an unconjugated antisense oligonucleotide in Phase 3 development for chronic hepatitis B virus (HBV) infection. In the Phase 2b study B-Together (NCT04676724), a subset of participants (pts) on nucleos(t)ide analogs (NAs) achieved a virological response following 12 or 24 weeks of BPV and 24 weeks of pegylated interferon α-2a (Peg-IFN) sequential therapy, which was sustained for 24 weeks following the end of Peg-IFN treatment. Pts with a complete response (CR) or partial response (PR) at the end of B-Together were eligible for the BSure long-term durability study (NCT04954859; ongoing). Here we present up to 33 months of follow-up data on the durability of response for B-Together complete responders (CRs) and partial responders (PRs) enrolled in B-Sure. Method: CR was defined as both hepatitis B surface antigen (HBsAg) < 0.05 IU/mL and HBV DNA < lower limit of quantification (LLOQ; < 20 IU/mL), and PR as 0.05 ≤ HBsAg < 100 IU/mL and HBV DNA < LLOQ, both for 24 weeks off BPV + Peg-IFN sequential therapy in B-Together. If eligible, pts discontinued NA treatment 3 months (mo) into B-Sure (≥ 9 mo from the end of BPV + Peg-IFN sequential therapy) and were followed to determine the achievement and durability of functional cure (FC; sustained HBsAg < 0.05 IU/mL and HBV DNA < LLOQ at 24 weeks off all HBV treatment). Adverse events (AEs) were recorded at each visit. Results: In total, 23 On-NA pts (13 CRs, 8 PRs and 2 non-responders) from B-Together were enrolled into B-Sure. Of the CRs, 12/13 discontinued NAs 3 mo into B-Sure; 9/12 maintained CR to 6 mo post–NA cessation, thus achieving FC. Of these, 7/7 (100%) have maintained 18 mo FC and 4/4 (100%) who reached the 33 mo B-Sure visit have maintained 24 mo FC (follow-up ongoing); no CRs restarted NAs during B-Sure. Of the PRs, 3/8 discontinued NAs 3 months into B-Sure; 1 PR achieved delayed FC at 18 mo post–NA cessation and has maintained 12 mo FC; 1 has maintained PR up to 24 mo post–NA cessation; 1 lost PR due to virological relapse and restarted NA treatment. Of all pts who discontinued NAs, none had alanine aminotransferase (ALT) ≥ 2x upper limit of normal. Post–NA cessation, no pt reported AEs of severe ALT flare. There was no indication that prior use of BPV had any latent adverse effects. Conclusion: FC is achieved after discontinuation of all HBV treatments and is durable for up to 24 mo in CRs in response to sequential BPV + Peg-IFN therapy, and no long-term safety signals were reported. Funding: GSK (206882).