Abstract | BACKGROUND: METHODS: RESULTS: At week 104, a total of 132 participants, including 112 with data that were prospectively collected at baseline, remained in the study. The mean annualized treated bleeding rate decreased by 84.5% from baseline (P<0.001) among the participants. From week 76 onward, the trajectory of the transgene-derived factor VIII activity showed first-order elimination kinetics; the model-estimated typical half-life of the transgene-derived factor VIII production system was 123 weeks (95% confidence interval, 84 to 232). The risk of joint bleeding was estimated among the trial participants; at a transgene-derived factor VIII level of 5 IU per deciliter measured with chromogenic assay, we expected that participants would have 1.0 episode of joint bleeding per year. At 2 years postinfusion, no new safety signals had emerged and no new serious adverse events related to treatment had occurred. CONCLUSIONS: The study data show the durability of factor VIII activity and bleeding reduction and the safety profile of valoctocogene roxaparvovec at least 2 years after the gene transfer. Models of the risk of joint bleeding suggest that the relationship between transgene-derived factor VIII activity and bleeding episodes is similar to that reported with the use of epidemiologic data for persons with mild-to-moderate hemophilia A. (Funded by BioMarin Pharmaceutical; GENEr8-1 ClinicalTrials.gov number, NCT03370913.).
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Authors | Johnny Mahlangu, Radoslaw Kaczmarek, Annette von Drygalski, Susan Shapiro, Sheng-Chieh Chou, Margareth C Ozelo, Gili Kenet, Flora Peyvandi, Michael Wang, Bella Madan, Nigel S Key, Michael Laffan, Amy L Dunn, Jane Mason, Doris V Quon, Emily Symington, Andrew D Leavitt, Johannes Oldenburg, Hervé Chambost, Mark T Reding, Kala Jayaram, Hua Yu, Reena Mahajan, Konstantia-Maria Chavele, Divya B Reddy, Joshua Henshaw, Tara M Robinson, Wing Yen Wong, Steven W Pipe, GENEr8-1 Trial Group |
Journal | The New England journal of medicine
(N Engl J Med)
Vol. 388
Issue 8
Pg. 694-705
(02 23 2023)
ISSN: 1533-4406 [Electronic] United States |
PMID | 36812433
(Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2023 Massachusetts Medical Society. |
Chemical References |
- Factor VIII
- Recombinant Fusion Proteins
- Valoctocogene Roxaparvovec
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Topics |
- Humans
- Male
- Factor VIII
(therapeutic use)
- Gene Transfer Techniques
- Half-Life
- Hemophilia A
(complications, drug therapy)
- Hemorrhage
(etiology, prevention & control)
- Recombinant Fusion Proteins
(therapeutic use)
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