Efficacy, safety, and quality of life 5 years after valoctocogene roxaparvovec gene transfer

Introduction The phase 3 GENEr8-1 trial (NCT03370913) is investigating the efficacy and safety of valoctocogene roxaparvovec, a gene therapy for severe hemophilia A (HA) that enables endogenous factor VIII (FVIII) production. After 4 years, mean (median) FVIII was 16.1 (6.7) IU/dL and 27.1 (13.5) IU/dL per chromogenic and one-stage assay, respectively. Compared with prior prophylaxis, mean annualized rate of treated bleeds and annualized FVIII infusions decreased 82.6% and 95.5% from baseline, respectively. The most common adverse events were mild, transient alanine aminotransferase (ALT) elevations. The aim of this study was to evaluate efficacy and safety of valoctocogene roxaparvovec 5 years post-treatment. Method GENEr8-1 is an open-label, multicenter, phase 3 trial that enrolled 134 adult men with severe HA (FVIII≤1 IU/dL) without FVIII inhibitors to receive a single infusion of 6x10 13 vg/kg valoctocogene roxaparvovec (intention-to-treat [ITT] population). FVIII activity was assessed in 132 human immunodeficiency virus (HIV)-negative participants. Bleeds and exogenous FVIII use were self-reported after discontinuing regular FVIII prophylaxis (planned for week 4 post-infusion). The primary analysis population for FVIII use and bleeding rates was 112 HIV-negative participants previously enrolled in a noninterventional study of FVIII prophylaxis. Safety and corticosteroid use were assessed in the ITT population. ALT elevation was defined as ALT above the upper limit of normal or≥1.5x baseline. Results Updated year-by-year and overall efficacy and safety data at least 5 years after treatment with valoctocogene roxaparvovec, reflecting ongoing endogenous FVIII expression, will be presented. Efficacy outcomes will include FVIII activity, bleeding and FVIII infusion rates, population- and participant-level return to prophylaxis data, and health-related quality of life data. Updated safety data, including adverse events and corticosteroid use, will also be presented. Conclusion Valoctocogene roxaparvovec provided improved hemostatic efficacy compared with FVIII prophylaxis through 5 years post-treatment with no new safety signals. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany