Efficacy, safety, and quality of life 4 years after valoctocogene roxaparvovec gene transfer for severe hemophilia A in the phase 3 GENEr8-1 trial

作者：Andrew D. Leavitt, Johnny Mahlangu, Priyanka Raheja, Emily Symington, Doris Quon, Adam Giermasz, María Fernanda López Fernández, Gili Kenet, Gillian Lowe, Nigel S. Key, Carolyn M. Millar, Steven W. Pipe, Bella Madan, Sheng‐Chieh Chou, Robert Klamroth, Jane Mason, Hérvè Chambost, Flora Peyvandi, Elaine M. Majerus, Dominic Pepperell, Christine Rivat, Hua Yu, Tara M. Robinson, Margareth C. Ozelo · 发表于：Research and Practice in Thrombosis and Haemostasis · 年份：2024 · DOI：10.1016/j.rpth.2024.102615 · 被引用次数：41 · 研究领域：Hemophilia Treatment and Research、Virus-based gene therapy research、Complement system in diseases

Background Valoctocogene roxaparvovec, an adeno-associated virus-mediated gene therapy for severe hemophilia A, enables endogenous factor (F)VIII expression and provides bleed protection. Objectives Determine valoctocogene roxaparvovec durability, efficacy, and safety 4 years after treatment. Methods In the phase 3 GENEr8-1 trial, 134 adult male persons with severe hemophilia A without inhibitors and previously using FVIII prophylaxis received a 6 × 10 13 vg/kg infusion of valoctocogene roxaparvovec. Efficacy endpoints included annualized bleed rate, annualized FVIII infusion rate, FVIII activity, and the Haemophilia-Specific Quality of Life Questionnaire for Adults. Adverse events and immunosuppressant use were assessed. Change from baseline was assessed after participants discontinued prophylaxis (scheduled for week 4). Results Median follow-up was 214.3 weeks; 2 participants discontinued since the previous data cutoff. Declines from baseline in mean treated annualized bleed rate (−82.6%; P < .0001) and annualized FVIII infusion rate (−95.5%; P < .0001) were maintained from previous years in the primary analysis population of 112 participants who enrolled from a noninterventional study. During year 4, 81 of 110 rollover participants experienced 0 treated bleeds. Week 208 mean and median chromogenic FVIII activity were 16.1 IU/dL and 6.7 IU/dL, respectively, in 130 modified intention-to-treat participants. Seven participants resumed prophylaxis since the previous data cutoff...