OBJECTIVE: To report the safety and efficacy of valoctocogene roxaparvovec 7 years after dosing in a phase 1/2 clinical study (NCT02576795).
METHODS: Males ≥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 × 1013 vg/kg; n = 7) and 6 (4 × 1013 vg/kg; n = 6) years.
RESULTS: In the last year, one participant in each cohort reported treatment-related adverse events (AEs): grade 1 (G1) hepatomegaly (6 × 1013), and G1 splenomegaly and G1 hepatic steatosis (4 × 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 × 1013 (n = 5) and 4 × 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 × 1013 and 4 × 1013 cohorts, respectively. Two participants (6 × 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.
CONCLUSIONS: The safety and efficacy of valoctocogene roxaparvovec remain generally consistent with previous reports, with good haemostatic control for most participants. Two participants returned to prophylaxis.
目的:在1/2期临床研究(NCT02576795)中,报告在给药7年后使用roxaparvovovec的安全性和有效性。
方法:患有重度HA(因子VIII[FVIII]≤1国际单位[IU]/dL)的男性≥18岁,先前接受过外源性FVIII且没有FVIII抑制剂或抗-AAV5抗体的病史,接受了valoctocogeneroxapavovec治疗,并随访7(6×1013vg/kg;n=7)和6(4×1013
结果:去年,每个队列中的一名参与者报告了治疗相关不良事件(AE):1级(G1级)肝肿大(6×1013),和G1脾肿大和G1肝脂肪变性(4×1013)。在所有后续行动中,平均年化治疗出血和外源性FVIII输注率比基线值低≥88%.在第7年和第6年,在6×1013(n=5)和4×1013(n=4)队列中,平均(中位数)FVIII活性(显色测定)为16.2(10.3)和6.7(7.2)IU/dL,分别,对应于轻度血友病。对6×1013和4×1013队列的FVIII活动的去年估计变化率的回归分析为-0.001和-0.07IU/dL/周,分别。两名参与者(6×1013)在第7年恢复预防:一名在自发性颈内动脉出血的非治疗相关的G4严重AE后,另一个管理出血和FVIII活动。
结论:Valoccogeneroxaparvovec的安全性和有效性与以前的报道基本一致,对大多数参与者有良好的止血控制。两名参与者恢复了预防。