Adults with Severe or Moderately Severe Hemophilia B Receiving Etranacogene Dezaparvovec in the HOPE-B Phase 3 Clinical Trial Continue to Experience a Stable Increase in Mean Factor IX Activity Levels and Durable Hemostatic Protection after 24 Months’ Follow-up

作者：Steven W. Pipe, Frank W.G. Leebeek, Michael Recht, Nigel S. Key, Susan Lattimore, Giancarlo Castaman, Michiel Coppens, David Cooper, Robert Gut, Sergio Slawka, Stephanie Verweij, Ricardo Dolmetsch, Yanyan Li, Paul E. Monahan, Wolfgang Miesbach · 发表于：Blood · 年份：2022 · DOI：10.1182/blood-2022-166135 · 被引用次数：11 · 研究领域：Virus-based gene therapy research、Hemophilia Treatment and Research、CAR-T cell therapy research

Introduction: Etranacogene dezaparvovec (formerly AMT-061), an investigational gene therapy for hemophilia B, is an adeno-associated virus serotype 5 (AAV5) vector, containing a codon-optimized, highly active factor IX (FIX) Padua R338L transgene under the control of a liver-specific promoter. The Phase 3 HOPE-B clinical trial (NCT03569891) of etranacogene dezaparvovec 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). However, the potential for liver-directed AAV to sustain long-term clotting factor expression remains unknown, with most human experience derived from early phase clinical trials. Aim: Efficacy and safety data is provided from the pivotal Phase 3 HOPE-B clinical trial over a period of 24 months of gene expression. Methods: In this open-label, single-arm study, adult male participants with severe or moderately severe hemophilia B (FIX≤2%), with or without pre-existing AAV5 neutralizing antibodies (NAbs), were infused with a single dose of etranacogene dezaparvovec (2x1013 gc/kg), following a ≥6-month lead-in period receiving FIX prophylaxis. FIX activity, annualized bleed rate (ABR), and FIX infusions were assessed frequently during the lead-in and first 12 months after receiving etranacogene dezaparvovec, then every 6 months during the long-term follow-up (Years 2-5). Adverse events (AEs) were recorded continuously....