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dc.contributor.authorPasi, K John
dc.contributor.authorLaffan, Michael
dc.contributor.authorRangarajan, Savita
dc.contributor.authorRobinson, Tara M
dc.contributor.authorMitchell, Nina
dc.contributor.authorLester, Will
dc.contributor.authorSymington, Emily
dc.contributor.authorMadan, Bella
dc.contributor.authorYang, Xinqun
dc.contributor.authorKim, Benjamin
dc.contributor.authorPierce, Glenn F
dc.contributor.authorWong, Wing Yen
dc.date.accessioned2021-11-08T17:25:16Z
dc.date.available2021-11-08T17:25:16Z
dc.date.issued2021-11
dc.date.submitted2021-03-02
dc.identifier.issn1351-8216
dc.identifier.otherhae14391
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/330454
dc.description.abstractINTRODUCTION: Valoctocogene roxaparvovec is an investigational AAV5-based factor VIII (FVIII) gene therapy that has demonstrated sustained clinical benefit in people with severe haemophilia A. AIM: To report safety, tolerability, efficacy, and quality of life (QOL) among participants who received valoctocogene roxaparvovec in a phase 1/2 clinical study (NCT02576795). METHODS: Men ≥18 years of age with severe haemophilia A (FVIII ≤1 IU/dl) without history of FVIII inhibitors or anti-AAV5 antibodies received a single infusion of valoctocogene roxaparvovec and were followed for 5 years (6 × 1013 vg/kg dose, n = 7) and 4 years (4 × 1013 vg/kg dose, n = 6). RESULTS: Over the past 2 years, few adverse events and no FVIII inhibitors were reported. Per chromogenic substrate (CSA) assay at years 5 and 4, four of seven and three of six participants in the 6 × 1013 and 4 × 1013 vg/kg cohorts, respectively, maintained median FVIII levels >5 IU/dl, corresponding to mild haemophilia. By regression analysis, rate of change in FVIII activity was -0.14 (95% confidence interval [CI]: -.32 to .03) IU/dl/wk in the 6 × 1013 vg/kg cohort in year 5 and -.06 (95% CI: -.14 to .01) IU/dl/wk in the 4 × 1013 vg/kg cohort in year 4. No participants resumed FVIII prophylaxis, and eight of 13 participants reported zero bleeds in the past 2 years. Improved QOL from baseline persisted in the 6 × 1013 vg/kg cohort; all six Haemo-QOL-A domain scores increased. For the 4 × 1013 vg/kg cohort, high baseline Haemo-QOL-A scores persisted. CONCLUSION: These results demonstrate transgene expression and haemostatic response for up to 5 years in individuals with haemophilia A.
dc.languageen
dc.publisherWiley
dc.subjectORIGINAL ARTICLE
dc.subjectORIGINAL ARTICLES
dc.subjecthaemophilia A
dc.subjectfactor VIII
dc.subjectgenetic therapy
dc.subjecthaemostasis
dc.subjectquality of life
dc.titlePersistence of haemostatic response following gene therapy with valoctocogene roxaparvovec in severe haemophilia A.
dc.typeArticle
dc.date.updated2021-11-08T17:25:15Z
prism.endingPage956
prism.issueIdentifier6
prism.publicationNameHaemophilia
prism.startingPage947
prism.volume27
dc.identifier.doi10.17863/CAM.77898
dcterms.dateAccepted2021-07-25
rioxxterms.versionofrecord10.1111/hae.14391
rioxxterms.versionAO
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.identifier.eissn1365-2516
cam.issuedOnline2021-08-11


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