Comparative Effectiveness of Valoctocogene Roxaparvovec and Prophylactic Factor VIII Replacement in Severe Hemophilia A

Introduction A prospective, non-interventional study (270-902) followed 294 adults with severe hemophilia A (SHA) receiving prophylactic factor VIII (FVIII). From these participants, 112 rolled over into a single-arm, multicenter, phase 3 trial (GENEr8-1; NCT03370913) that evaluated efficacy and saf...

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Bibliographic Details
Published in:Advances in therapy 2024-06, Vol.41 (6), p.2267-2281
Main Authors: Oldenburg, Johannes, Chambost, Herve, Liu, Hai, Hawes, Charles, You, Xiaojun, Yang, Xinqun, Newman, Vanessa, Robinson, Tara M., Hatswell, Anthony J., Hinds, David, Santos, Sandra, Ozelo, Margareth
Format: Article
Language:English
Subjects:
Adult
Cardiology
Endocrinology
Factor VIII - therapeutic use
Female
Genetic Therapy - methods
Hemophilia A - complications
Hemophilia A - drug therapy
Hemorrhage - prevention & control
Humans
Internal Medicine
Male
Medicine
Medicine & Public Health
Middle Aged
NCT
NCT03370913
Oncology
Original Research
Pharmacology/Toxicology
Prospective Studies
Rheumatology
Treatment Outcome
Young Adult
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Summary:Introduction A prospective, non-interventional study (270-902) followed 294 adults with severe hemophilia A (SHA) receiving prophylactic factor VIII (FVIII). From these participants, 112 rolled over into a single-arm, multicenter, phase 3 trial (GENEr8-1; NCT03370913) that evaluated efficacy and safety of valoctocogene roxaparvovec, a gene therapy that provides endogenous FVIII in individuals with SHA. Participants from 270-902 who did not roll over provide an opportunity for a contemporaneous external control. Therefore, the comparative effectiveness of valoctocogene roxaparvovec vs FVIII prophylaxis was evaluated using propensity scoring (PS). Methods This post hoc analysis compared 112 participants from GENEr8-1 (treated cohort) to 73 participants in 270-902 who did not enroll in GENEr8-1 (control cohort). The primary analysis used standardized mortality ratio weighting to re-weight baseline characteristics of the control cohort to better match the treated cohort. Mean annualized bleeding rates (ABR) for treated and all bleeds were compared between cohorts along with the proportion of participants with zero bleeds (treated and all bleeds). Sensitivity and scenario analyses were also conducted. Results PS adjustments reduced differences in baseline characteristics between cohorts. Mean treated (4.40 vs 0.85; P  
ISSN:0741-238X
1865-8652
1865-8652
DOI:10.1007/s12325-024-02834-9