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@article{Ozelo:2022:10.1056/NEJMoa2113708,
author = {Ozelo, MC and Mahlangu, J and Pasi, KJ and Giermasz, A and Leavitt, AD and Laffan, M and Symington, E and Quon, DV and Wang, J-D and Peerlinck, K and Pipe, SW and Madan, B and Key, NS and Pierce, GF and O'Mahony, B and Kaczmarek, R and Henshaw, J and Lawal, A and Jayaram, K and Huang, M and Yang, X and Wong, WY and Kim, B and GENEr8-1, Trial Group},
doi = {10.1056/NEJMoa2113708},
journal = {The New England journal of medicine},
pages = {1013--1025},
title = {Valoctocogene roxaparvovec gene therapy for hemophilia A.},
url = {http://dx.doi.org/10.1056/NEJMoa2113708},
volume = {386},
year = {2022}
}

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TY  - JOUR
AB  - BACKGROUND: Valoctocogene roxaparvovec (AAV5-hFVIII-SQ) is an adeno-associated virus 5 (AAV5)-based gene-therapy vector containing a coagulation factor VIII complementary DNA driven by a liver-selective promoter. The efficacy and safety of the therapy were previously evaluated in men with severe hemophilia A in a phase 1-2 dose-escalation study. METHODS: We conducted an open-label, single-group, multicenter, phase 3 study to evaluate the efficacy and safety of valoctocogene roxaparvovec in men with severe hemophilia A, defined as a factor VIII level of 1 IU per deciliter or lower. Participants who were at least 18 years of age and did not have preexisting anti-AAV5 antibodies or a history of development of factor VIII inhibitors and who had been receiving prophylaxis with factor VIII concentrate received a single infusion of 6×1013 vector genomes of valoctocogene roxaparvovec per kilogram of body weight. The primary end point was the change from baseline in factor VIII activity (measured with a chromogenic substrate assay) during weeks 49 through 52 after infusion. Secondary end points included the change in annualized factor VIII concentrate use and bleeding rates. Safety was assessed as adverse events and laboratory test results. RESULTS: Overall, 134 participants received an infusion and completed more than 51 weeks of follow-up. Among the 132 human immunodeficiency virus-negative participants, the mean factor VIII activity level at weeks 49 through 52 had increased by 41.9 IU per deciliter (95% confidence interval [CI], 34.1 to 49.7; P<0.001; median change, 22.9 IU per deciliter; interquartile range, 10.9 to 61.3). Among the 112 participants enrolled from a prospective noninterventional study, the mean annualized rates of factor VIII concentrate use and treated bleeding after week 4 had decreased after infusion by 98.6% and 83.8%, respectively (P<0.001 for both comparisons). All the participants had at least one adverse event; 22 of 134 (16.4%) repor
AU  - Ozelo,MC
AU  - Mahlangu,J
AU  - Pasi,KJ
AU  - Giermasz,A
AU  - Leavitt,AD
AU  - Laffan,M
AU  - Symington,E
AU  - Quon,DV
AU  - Wang,J-D
AU  - Peerlinck,K
AU  - Pipe,SW
AU  - Madan,B
AU  - Key,NS
AU  - Pierce,GF
AU  - O'Mahony,B
AU  - Kaczmarek,R
AU  - Henshaw,J
AU  - Lawal,A
AU  - Jayaram,K
AU  - Huang,M
AU  - Yang,X
AU  - Wong,WY
AU  - Kim,B
AU  - GENEr8-1,Trial Group
DO  - 10.1056/NEJMoa2113708
EP  - 1025
PY  - 2022///
SN  - 0028-4793
SP  - 1013
TI  - Valoctocogene roxaparvovec gene therapy for hemophilia A.
T2  - The New England journal of medicine
UR  - http://dx.doi.org/10.1056/NEJMoa2113708
UR  - https://www.ncbi.nlm.nih.gov/pubmed/35294811
UR  - https://www.nejm.org/doi/pdf/10.1056/NEJMoa2113708?articleTools=true
UR  - http://hdl.handle.net/10044/1/96380
VL  - 386
ER  -

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