背景：Valoctocogeneroxapavovec是一种腺相关病毒载体血清型5（AAV5）介导的基因疗法，已被批准用于严重的A型血友病（HA）。
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。
BACKGROUND: Valoctocogene roxaparvovec is an adeno-associated virus vector serotype 5 (AAV5)-mediated gene therapy approved for severe haemophilia A (HA).
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.
