Three-year outcomes of valoctocogene roxaparvovec gene therapy for hemophilia A.
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Author
Madan, BellaOzelo, Margareth C
Raheja, Priyanka
Symington, Emily
Quon, Doris V
Leavitt, Andrew D
Pipe, Steven W
Lowe, Gillian
Kenet, Gili
Reding, Mark T
Mason, Jane
Wang, Michael
von Drygalski, Annette
Klamroth, Robert
Shapiro, Susan
Chambost, Hervé
Dunn, Amy L
Oldenburg, Johannes
Chou, Sheng-Chieh
Peyvandi, Flora
Millar, Carolyn M
Osmond, Dane
Yu, Hua
Dashiell-Aje, Ebony
Robinson, Tara M
Mahlangu, Johnny
Publication date
2024-04-12Subject
Haematology
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Background: Valoctocogene roxaparvovec transfers a human factor (F)VIII coding sequence into hepatocytes of people with severe hemophilia A to provide bleeding protection. Objectives: To present 3-year efficacy and safety in the multicenter, open-label, single-arm, phase 3 GENEr8-1 trial. Methods: GENEr8-1 enrolled 134 adult males with severe hemophilia A who were receiving FVIII prophylaxis. Efficacy endpoints included annualized bleeding rate, annualized FVIII utilization, FVIII activity (chromogenic substrate assay; imputed as 1 IU/dL at baseline and 0 IU/dL after discontinuation), and the Haemophilia-Specific Quality of Life Questionnaire for Adults. Safety was assessed by adverse events (AEs). Results: At week 156, 131 of 134 participants remained in the study; overall, 17 of 134 resumed prophylaxis. Mean annualized bleeding rate for treated bleeds decreased from 4.8 (SD, 6.5) bleeds/y at baseline to 0.8 (SD, 2.3; P < .0001) bleeds/y after prophylaxis (prophylaxis cessation to last follow-up) and 0.97 (SD, 3.48) bleeds/y during year 3. Annualized FVIII utilization decreased 96.8% from baseline after prophylaxis and 94.2% during year 3. At week 156, mean and median FVIII activity were 18.4 (SD, 30.8) and 8.3 IU/dL, respectively. FVIII activity decrease was lower between years 2 and 3 than between years 1 and 2. At the end of year 3, clinically meaningful improvements in the Haemophilia-Specific Quality of Life Questionnaire for Adults Total Score were observed (mean change from baseline, 6.6; 95% CI, 4.24-8.87; P < .0001). Mild alanine aminotransferase elevations remained the most common AE during year 3 (23.7% of participants). A serious AE of B-cell acute lymphoblastic leukemia was considered unrelated to treatment. Conclusion: Hemostatic efficacy was maintained, and safety remained unchanged from previous years.Citation
Madan B, Ozelo MC, Raheja P, Symington E, Quon DV, Leavitt AD, Pipe SW, Lowe G, Kenet G, Reding MT, Mason J, Wang M, von Drygalski A, Klamroth R, Shapiro S, Chambost H, Dunn AL, Oldenburg J, Chou SC, Peyvandi F, Millar CM, Osmond D, Yu H, Dashiell-Aje E, Robinson TM, Mahlangu J. Three-year outcomes of valoctocogene roxaparvovec gene therapy for hemophilia A. J Thromb Haemost. 2024 Jul;22(7):1880-1893. doi: 10.1016/j.jtha.2024.04.001. Epub 2024 Apr 12.Type
ArticleAdditional Links
http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1538-7836PMID
38614387Publisher
Elsevierae974a485f413a2113503eed53cd6c53
10.1016/j.jtha.2024.04.001