Article Dans Une Revue Research and Practice in Thrombosis and Haemostasis Année : 2024

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

Andrew Leavitt
  • Fonction : Auteur
Johnny Mahlangu
  • Fonction : Auteur
Priyanka Raheja
  • Fonction : Auteur
Emily Symington
  • Fonction : Auteur
Doris Quon
  • Fonction : Auteur
Adam Giermasz
  • Fonction : Auteur
Gili Kenet
  • Fonction : Auteur
Gillian Lowe
  • Fonction : Auteur
Nigel Key
  • Fonction : Auteur
Carolyn Millar
  • Fonction : Auteur
Steven Pipe
  • Fonction : Auteur
Bella Madan
  • Fonction : Auteur
Sheng-Chieh Chou
  • Fonction : Auteur
Robert Klamroth
  • Fonction : Auteur
Jane Mason
  • Fonction : Auteur
Flora Peyvandi
  • Fonction : Auteur
Elaine Majerus
  • Fonction : Auteur
Dominic Pepperell
  • Fonction : Auteur
Christine Rivat
  • Fonction : Auteur
Hua Yu
  • Fonction : Auteur
Tara Robinson
  • Fonction : Auteur
Margareth Ozelo
  • Fonction : Auteur

Résumé

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 × 1013 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. Mean change from baseline to week 208 in Haemophilia-Specific Quality of Life Questionnaire for Adults Total Score (P < .0001) remained clinically meaningful for modified intention-to-treat participants. Alanine aminotransferase elevation was the most common adverse event during year 4 (56/131 participants); none required immunosuppressants. Conclusion Valoctocogene roxaparvovec provides persistent FVIII expression, hemostatic control, and health-related quality of life improvements with no new safety signals.

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hal-04948564 , version 1 (19-02-2025)

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Andrew Leavitt, Johnny Mahlangu, Priyanka Raheja, Emily Symington, Doris Quon, et al.. Efficacy, safety, and quality of life 4 years after valoctocogene roxaparvovec gene transfer for severe hemophilia A in the phase 3 GENEr8-1 trial. Research and Practice in Thrombosis and Haemostasis, 2024, 8 (8), pp.102615. ⟨10.1016/j.rpth.2024.102615⟩. ⟨hal-04948564⟩
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