Persistence of haemostatic response following gene therapy with valoctocogene roxaparvovec in severe haemophilia A.
dc.contributor.author | Pasi, K John | |
dc.contributor.author | Laffan, Michael | |
dc.contributor.author | Rangarajan, Savita | |
dc.contributor.author | Robinson, Tara M | |
dc.contributor.author | Mitchell, Nina | |
dc.contributor.author | Lester, Will | |
dc.contributor.author | Symington, Emily | |
dc.contributor.author | Madan, Bella | |
dc.contributor.author | Yang, Xinqun | |
dc.contributor.author | Kim, Benjamin | |
dc.contributor.author | Pierce, Glenn F | |
dc.contributor.author | Wong, Wing Yen | |
dc.date.accessioned | 2021-11-08T17:25:16Z | |
dc.date.available | 2021-11-08T17:25:16Z | |
dc.date.issued | 2021-11 | |
dc.date.submitted | 2021-03-02 | |
dc.identifier.issn | 1351-8216 | |
dc.identifier.other | hae14391 | |
dc.identifier.uri | https://www.repository.cam.ac.uk/handle/1810/330454 | |
dc.description.abstract | INTRODUCTION: 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.language | en | |
dc.publisher | Wiley | |
dc.subject | ORIGINAL ARTICLE | |
dc.subject | ORIGINAL ARTICLES | |
dc.subject | haemophilia A | |
dc.subject | factor VIII | |
dc.subject | genetic therapy | |
dc.subject | haemostasis | |
dc.subject | quality of life | |
dc.title | Persistence of haemostatic response following gene therapy with valoctocogene roxaparvovec in severe haemophilia A. | |
dc.type | Article | |
dc.date.updated | 2021-11-08T17:25:15Z | |
prism.endingPage | 956 | |
prism.issueIdentifier | 6 | |
prism.publicationName | Haemophilia | |
prism.startingPage | 947 | |
prism.volume | 27 | |
dc.identifier.doi | 10.17863/CAM.77898 | |
dcterms.dateAccepted | 2021-07-25 | |
rioxxterms.versionofrecord | 10.1111/hae.14391 | |
rioxxterms.version | AO | |
rioxxterms.version | VoR | |
rioxxterms.licenseref.uri | http://creativecommons.org/licenses/by-nc/4.0/ | |
dc.identifier.eissn | 1365-2516 | |
cam.issuedOnline | 2021-08-11 |
Files in this item
This item appears in the following Collection(s)
-
Jisc Publications Router
This collection holds Cambridge publications received from the Jisc Publications Router