Three-year outcomes of valoctocogene roxaparvovec gene therapy for hemophilia A.
J Thromb Haemost
; 22(7): 1880-1893, 2024 Jul.
Article
de En
| MEDLINE
| ID: mdl-38614387
ABSTRACT
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.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Qualité de vie
/
Facteur VIII
/
Thérapie génétique
/
Hémophilie A
/
Hémorragie
Limites:
Adolescent
/
Adult
/
Humans
/
Male
/
Middle aged
Langue:
En
Journal:
J Thromb Haemost
/
J. thromb. haemost
/
Journal of thrombosis and haemostasis
Sujet du journal:
HEMATOLOGIA
Année:
2024
Type de document:
Article
Pays de publication:
Royaume-Uni