Adults with severe or moderately severe haemophilia B receiving etranacogene dezaparvovec in the HOPE-B phase 3 trial experience a stable increase in mean Factor IX activity levels and durable haemostatic protection after 24 months’ follow-up

作者：W S Pipe, WG F Leebeek, Michael Recht, S N Key, Susan Lattimore, Giancarlo Castaman, M Coppens, David Cooper, Robert Gut, Sergio Slawka, Stephanie Verweij, Ricardo Dolmetsch, Y Li, PE Monahan, Wolfgang Miesbach · 发表于：Hämostaseologie · 年份：2023 · DOI：10.1055/s-0042-1760523 · 被引用次数：1 · 研究领域：Hemophilia Treatment and Research、Virus-based gene therapy research

Introduction Etranacogene dezaparvovec (formerly AMT-061) is an investigational gene therapy for haemophilia B comprising an adeno-associated virus serotype 5 (AAV5) vector and a codon-optimised factor IX (FIX) Padua R338L transgene with a liver-specific promoter. The Phase 3 HOPE-B trial (NCT03569891) aims to assess the efficacy and safety of etranacogene dezaparvovec. Method In this open-label, single-arm trial, adult males with severe/moderately severe haemophilia B (FIX ≤2%), with/without pre-existing AAV5 neutralising antibodies (NAbs), received etranacogene dezaparvovec (single dose; 2x1013 gc/kg) following a ≥6-month lead-in period on FIX prophylaxis. FIX activity, annualised bleed rate (ABR), and FIX infusions were assessed frequently during the lead-in and first 12 months after dosing, then every 6 months during long-term follow-up (Years 2–5). Adverse events (AEs) were recorded. Results Of the 54 participants, 53 received the full dose and 52 completed 24 months of follow-up. At 464 days (~15 months) post-infusion, one 75-year-old participant died from cardiogenic shock, preceded by a urinary tract infection (unrelated to treatment). Of the 54 participants, 52 (96.3%) discontinued and remained free of continuous FIX prophylaxis from Day 21 to Months 7–24, including 20 participants with baseline AAV5 NAb titres <1:700. One participant with a markedly higher AAV5 NAbs titre (1:3212) and one participant who received a partial vector dose (due to an infusion-related rea...