Valoctocogene roxaparvovec gene therapy provides durable haemostatic control for up to 7 years for haemophilia A

IntroductionValoctocogene roxaparvovec is an adeno-associated virus vector serotype 5 (AAV5)-mediated gene therapy approved for severe haemophilia A (HA).AimTo report the safety and efficacy of valoctocogene roxaparvovec 7 years after dosing in a phase 1/2 clinical study (NCT02576795).MethodsMales >= 18 years with severe HA (factor VIII [FVIII] <= 1 international unit [IU]/dL) who were previously receiving exogenous FVIII and had no history of FVIII inhibitors or anti-AAV5 antibodies received valoctocogene roxaparvovec treatment and were followed for 7 (6 x 1013 vg/kg; n = 7) and 6 (4 x 1013 vg/kg; n = 6) years.ResultsIn the last year, one participant in each cohort reported treatment-related adverse events (AEs): grade 1 (G1) hepatomegaly (6 x 1013), and G1 splenomegaly and G1 hepatic steatosis (4 x 1013). During all follow-up, mean annualized treated bleeds and exogenous FVIII infusion rates were >= 88% lower than baseline values. At years 7 and 6, mean (median) FVIII activity (chromogenic assay) was 16.2 (10.3) and 6.7 (7.2) IU/dL in the 6 x 1013 (n = 5) and 4 x 1013 (n = 4) cohorts, respectively, corresponding to mild haemophilia. Regression analyses of the last year estimated rate of change in FVIII activity was -0.001 and -0.07 IU/dL/week for the 6 x 1013 and 4 x 1013 cohorts, respectively. Two participants (6 x 1013) resumed prophylaxis in year 7: one after a non-treatment-related G4 serious AE of spontaneous internal carotid artery bleed, and the other to manage bleeds and FVIII activity.ConclusionsThe safety and efficacy of valoctocogene roxaparvovec remain generally consistent with previous reports, with good haemostatic control for most participants. Two participants returned to prophylaxis.