Durability of Bleeding Protection and Factor IX Activity Levels Are Demonstrated in Individuals with and without Adeno-Associated Virus Serotype 5 Neutralizing Antibodies (Titers <1:700) with Comparable Safety in the Phase 3 HOPE-B Clinical Trial of Etranacogene Dezaparvovec Gene Therapy for Hemophilia B

作者：Steven W. Pipe, Frank W.G. Leebeek, Michael Recht, Nigel S. Key, Susan Lattimore, Giancarlo Castaman, David Cooper, Stephanie Verweij, Ricardo Dolmetsch, Jacqueline Tarrant, Yanyan Li, Paul E. Monahan, Wolfgang Miesbach · 发表于：Blood · 年份：2022 · DOI：10.1182/blood-2022-166745 · 被引用次数：4 · 研究领域：CAR-T cell therapy research、Virus-based gene therapy research、Hemophilia Treatment and Research

Introduction: Pre-existing adeno-associated virus (AAV) neutralizing antibodies (NAbs) have limited the efficacy of AAV-based gene therapy in prior clinical applications, including in hemophilia. A unique aspect of the Phase 3 HOPE-B clinical trial (NCT03569891) assessing etranacogene dezaparvovec gene therapy, an AAV serotype 5 vector expressing Padua factor IX (FIX), was the enrollment of participants regardless of their baseline AAV5 NAb status. The HOPE-B clinical trial met its primary efficacy endpoint, providing hemostatic protection superior to standard of care FIX prophylaxis over 52 weeks of follow-up after stable FIX Padua expression (defined as Months 7-18). Aim: Assess efficacy and safety of etranacogene dezaparvovec in HOPE-B participants with (NAb+) and without (NAb-) pre-existing AAV5 NAbs over 18 and 24 months of follow-up. Methods: Adult male participants with severe or moderately severe hemophilia B (FIX ≤2%), NAb+ or NAb-, were treated in the Phase 3, open-label, single-arm, HOPE-B trial with a single intravenous infusion of etranacogene dezaparvovec (2x1013 gc/kg), following a ≥6-month lead-in period receiving FIX prophylaxis. FIX activity, annualized bleed rate (ABR), and use of infused replacement FIX concentrates were assessed regularly during the lead-in and the first 12 months after receiving etranacogene dezaparvovec, then every 6 months during the long-term follow-up (Years 2-5). Adverse events were recorded continuously. Although not an exclusion c...