181PAAV gene therapy with delandistrogene moxeparvovec in two-year old patients with Duchenne muscular dystrophy: clinical efficacy measured by digital endpoints

IF 2.8 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders Pub Date : 2025-09-01 DOI:10.1016/j.nmd.2025.105534

C. Grotski , L. Servais , D. Eggenspieler , E. Henricson , P. Strijbos , P. Sidiropoulos , R. Finkel , C. McDonald

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Abstract

Clinical assessment of the efficacy of AAV microdystrophin gene therapy in very young Duchenne muscular dystrophy patients below the age of 4 years is a challenge. We utilized the EMA qualified digital endpoint Stride velocity 95th centile (SV95c) measured by the Syde wearable device (SYSNAV) to assess the clinical efficacy over 12 months following administration of AAV microdystrophin gene therapy with delandistrogene moxeparvovec in very young ambulatory patients with DMD. Two patients with Duchenne muscular dystrophy (2 years and 2 years 3 months at baseline/pre-infusion) were treated with delandistrogene moxeparvovec as part of the Sarepta Therapeutics Study SRP-9001-103 (ENDEAVOR). Under a separate protocol, patients wore the Syde device for two to 4 weeks consecutively prior to treatment and at 3-, 6-, 9- and 12-months post-treatment. External comparator data were obtained from the ActiLiège-Next study (NCT05982119), a multicenter natural history study of ankle wearable technology in DMD patients <4 years. Adherence to bilateral ankle monitoring was excellent with > 50 hours of data collected at all time points. Baseline values of SV95c were 1.27 m/s and 1.13 m/s in the treated patients in comparison to a mean +SD of 1.31 (+0.25) m/s in n=13 external comparators. The 9-month change in SV95c was +0.36 m/s and +0.35 m/s in the two treated patients versus mean 9-month changes of +0.08 m/s (+ 0.14) in 3 steroid-treated and +0.23 m/s (+ 0.10) in 8 steroid naïve comparators of up to four years of age. Continued improvements in treated patients beyond that observed in natural history comparators have been seen at 12 months. Improvements were documented using SV95c in two of the youngest delandistrogene moxeparvovec treated patients with DMD to date and the improvements in mobility in the community over 9 to 12 months appear to be greater than that seen with or without steroids in very young external comparators. Use of ankle wearable technology providing the SV95c digital endpoint appears promising as an approach to assessing clinical efficacy of gene therapy in very young patients with DMD ages two years and above.

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181PAAV基因治疗2岁Duchenne型肌营养不良患者的数字终点临床疗效

临床评估AAV微营养不良蛋白基因治疗4岁以下非常年轻的杜氏肌营养不良症患者的疗效是一个挑战。我们利用Syde可穿戴设备（SYSNAV）测量的EMA合格数字终点Stride - velocity 95百分位（SV95c）来评估在非常年轻的动态DMD患者中使用delandistrogene moxparvovec进行AAV微营养不良蛋白基因治疗后12个月的临床疗效。作为Sarepta治疗研究SRP-9001-103 （ENDEAVOR）的一部分，2例Duchenne肌营养不良患者（基线/输注前2年和2年3个月）接受delandistrogene moxeparvovec治疗。在一个单独的方案下，患者在治疗前和治疗后3、6、9和12个月连续佩戴Syde装置2至4周。外部比较数据来自actili - next研究（NCT05982119），这是一项为期4年的DMD患者踝关节可穿戴技术多中心自然历史研究。双侧踝关节监测的依从性非常好，在所有时间点收集了50小时的数据。在接受治疗的患者中，SV95c的基线值分别为1.27 m/s和1.13 m/s，而在n=13个外部比较者中，平均+SD为1.31 (+0.25)m/s。在两名接受治疗的患者中，SV95c的9个月变化分别为+0.36 m/s和+0.35 m/s，而在3名接受类固醇治疗的患者中，SV95c的9个月平均变化为+0.08 m/s(+ 0.14)，在8名年龄不超过4岁的类固醇naïve比较者中，SV95c的9个月平均变化为+0.23 m/s（+ 0.10）。在12个月时，治疗患者的持续改善超过了在自然史比较中观察到的。迄今为止，在两名最年轻的delandistrogene moxparvovec治疗的DMD患者中，使用SV95c有改善记录，并且在9至12个月内，社区活动能力的改善似乎大于在非常年轻的外部比较者中使用或不使用类固醇。使用提供SV95c数字端点的脚踝可穿戴技术，作为评估年龄在2岁及以上的非常年轻的DMD患者基因治疗临床疗效的方法，似乎很有希望。

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来源期刊

Neuromuscular Disorders 医学-临床神经学

CiteScore

4.60

自引率

3.60%

发文量

543

审稿时长

53 days

期刊介绍： This international, multidisciplinary journal covers all aspects of neuromuscular disorders in childhood and adult life (including the muscular dystrophies, spinal muscular atrophies, hereditary neuropathies, congenital myopathies, myasthenias, myotonic syndromes, metabolic myopathies and inflammatory myopathies). The Editors welcome original articles from all areas of the field: • Clinical aspects, such as new clinical entities, case studies of interest, treatment, management and rehabilitation (including biomechanics, orthotic design and surgery). • Basic scientific studies of relevance to the clinical syndromes, including advances in the fields of molecular biology and genetics. • Studies of animal models relevant to the human diseases. The journal is aimed at a wide range of clinicians, pathologists, associated paramedical professionals and clinical and basic scientists with an interest in the study of neuromuscular disorders.