Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Department of Veterans Affairs Medical Center, Pittsburgh, Pennsylvania.
J Neuromuscul Dis. 2022;9(4):493-501. doi: 10.3233/JND-220811.
Duchenne muscular dystrophy (DMD) is a rare, genetic disease caused by mutations in the DMD gene resulting in an absence of functional dystrophin protein. Viltolarsen, an exon 53 skipping therapy, has been shown to increase endogenous dystrophin levels. Herein, long-term (>2 years) functional outcomes in viltolarsen treated patients were compared to a matched historical control group.
To evaluate long-term efficacy and safety of the anti-sense oligonucleotide viltolarsen in the treatment of patients with DMD amenable to exon 53 skipping therapy.
This trial (NCT03167255) is the extension of a previously published 24-week trial in North America (NCT02740972) that examined dystrophin levels, timed function tests compared to a matched historical control group (Cooperative International Neuromuscular Research Group Duchenne Natural History Study, CINRG DNHS), and safety in boys 4 to < 10 years (N = 16) with DMD amenable to exon 53 skipping who were treated with viltolarsen. Both groups were treated with glucocorticoids. All 16 participants elected to enroll in this long-term trial (up to 192 weeks) to continue evaluation of motor function and safety.
Time to stand from supine and time to run/walk 10 meters showed stabilization from baseline through week 109 for viltolarsen-treated participants whereas the historical control group showed decline (statistically significant differences for multiple timepoints). Safety was similar to that observed in the previous 24-week trial, which was predominantly mild. There have been no treatment-related serious adverse events and no discontinuations.
Based on these results at over 2 years, viltolarsen can be a new treatment option for patients with DMD amenable to exon 53 skipping.
杜氏肌营养不良症（DMD）是一种罕见的遗传性疾病，由 DMD 基因突变导致功能性肌营养不良蛋白缺失引起。Viltolarsen 是一种外显子 53 跳跃治疗药物，已被证明可提高内源性肌营养不良蛋白水平。在此，对接受 viltolarsen 治疗的患者进行了超过 2 年的长期（>2 年）功能结果比较，并与匹配的历史对照组进行比较。
评估抗肌萎缩蛋白反义寡核苷酸 viltolarsen 治疗可进行外显子 53 跳跃治疗的 DMD 患者的长期疗效和安全性。
本试验（NCT03167255）是之前在北美进行的为期 24 周的试验（NCT02740972）的扩展，该试验检查了肌营养不良蛋白水平、与匹配的历史对照组（CINRG DNHS）进行的定时功能测试以及 4 至<10 岁的可进行外显子 53 跳跃治疗的 DMD 男孩（N=16）的安全性，这些患者接受了 viltolarsen 治疗。两组均接受糖皮质激素治疗。所有 16 名参与者选择参加这项长期试验（长达 192 周），以继续评估运动功能和安全性。
从仰卧位到站立和从仰卧位到跑/走 10 米的时间显示，viltolarsen 治疗组从基线到第 109 周稳定，而历史对照组显示下降（在多个时间点有统计学显著差异）。安全性与之前的 24 周试验相似，主要为轻度。没有治疗相关的严重不良事件，也没有停药。
基于超过 2 年的这些结果，viltolarsen 可以成为适合外显子 53 跳跃治疗的 DMD 患者的新治疗选择。
