Imperial College London
Alternate

ProfessorMikeLaffan

Faculty of Medicine, Department of Immunology and Inflammation

Visiting Professor
 
 
 
//

Contact

 

+44 (0)20 3313 2178m.laffan

 
 
//

Assistant

 

Mrs Lisa Pape +44 (0)20 3313 1320

 
//

Location

 

5S5bHammersmith HospitalHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Pasi:2021:10.1111/hae.14391,
author = {Pasi, KJ and Laffan, M and Rangarajan, S and Robinson, TM and Mitchell, N and Lester, W and Symington, E and Madan, B and Yang, X and Kim, B and Pierce, GF and Wong, WY},
doi = {10.1111/hae.14391},
journal = {Haemophilia},
pages = {947--956},
title = {Persistence of haemostatic response following gene therapy with valoctocogene roxaparvovec in severe haemophilia A},
url = {http://dx.doi.org/10.1111/hae.14391},
volume = {27},
year = {2021}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - IntroductionValoctocogene roxaparvovec is an investigational AAV5-based factor VIII (FVIII) gene therapy that has demonstrated sustained clinical benefit in people with severe haemophilia A.AimTo report safety, tolerability, efficacy, and quality of life (QOL) among participants who received valoctocogene roxaparvovec in a phase 1/2 clinical study (NCT02576795).MethodsMen ≥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).ResultsOver 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.ConclusionThese results demonstrate transgene expression and haemostatic response for up to 5 years in individuals with haemophilia A.
AU  - Pasi,KJ
AU  - Laffan,M
AU  - Rangarajan,S
AU  - Robinson,TM
AU  - Mitchell,N
AU  - Lester,W
AU  - Symington,E
AU  - Madan,B
AU  - Yang,X
AU  - Kim,B
AU  - Pierce,GF
AU  - Wong,WY
DO  - 10.1111/hae.14391
EP  - 956
PY  - 2021///
SN  - 1351-8216
SP  - 947
TI  - Persistence of haemostatic response following gene therapy with valoctocogene roxaparvovec in severe haemophilia A
T2  - Haemophilia
UR  - http://dx.doi.org/10.1111/hae.14391
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000683689200001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://onlinelibrary.wiley.com/doi/10.1111/hae.14391
UR  - http://hdl.handle.net/10044/1/96385
VL  - 27
ER  -
Download