Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Department of Veterans Affairs Medical Center, Pittsburgh, PA, USA.
J Neuromuscul Dis. 2023;10(3):439-447. doi: 10.3233/JND-221656.
Duchenne muscular dystrophy (DMD) is caused by DMD gene mutations, resulting in absence of functional dystrophin protein. Viltolarsen, an exon 53 skipping therapy, significantly increased dystrophin levels in patients with DMD. Presented here are completed study results of > 4 years of functional outcomes in viltolarsen-treated patients compared to a historical control group (Cooperative International Neuromuscular Research Group Duchenne Natural History Study [CINRG DNHS]).
To evaluate the efficacy and safety of viltolarsen for an additional 192 weeks in boys with DMD.
This phase 2, open-label, 192-week long-term extension (LTE) study (NCT03167255) evaluated the efficacy and safety of viltolarsen in participants aged 4 to < 10 years at baseline with DMD amenable to exon 53 skipping. All 16 participants from the initial 24-week study enrolled into this LTE. Timed function tests were compared to the CINRG DNHS group. All participants received glucocorticoid treatment. The primary efficacy outcome was time to stand from supine (TTSTAND). Secondary efficacy outcomes included additional timed function tests. Safety was continuously assessed.
For the primary efficacy outcome (TTSTAND), viltolarsen-treated patients showed stabilization of motor function over the first two years and significant slowing of disease progression over the following two years compared with the CINRG DNHS control group which declined. Viltolarsen was well tolerated, with most reported treatment-emergent adverse events being mild or moderate. No participants discontinued drug during the study.
Based on the results of this 4-year LTE, viltolarsen can be an important treatment strategy for DMD patients amenable to exon 53 skipping.
杜氏肌营养不良症（DMD）是由 DMD 基因突变引起的，导致功能性肌营养不良蛋白缺失。Viltolarsen 是一种外显子 53 跳跃治疗方法，可显著提高 DMD 患者的肌营养不良蛋白水平。这里介绍了 viltolarsen 治疗患者与历史对照组（合作国际神经肌肉研究组 Duchenne 自然史研究[CINRG DNHS]）相比，经过 4 年以上功能结果的完成研究结果。
评估 viltolarsen 在 DMD 男孩中额外治疗 192 周的疗效和安全性。
这项为期 2 年、开放标签、192 周的长期扩展（LTE）研究（NCT03167255）评估了 viltolarsen 在基线时年龄为 4 至<10 岁、适合外显子 53 跳跃的 DMD 患者中的疗效和安全性。最初的 24 周研究中的所有 16 名参与者都参加了这个 LTE。定时功能测试与 CINRG DNHS 组进行比较。所有参与者均接受糖皮质激素治疗。主要疗效终点为从仰卧位到站立的时间（TTSTAND）。次要疗效终点包括其他定时功能测试。安全性持续评估。
对于主要疗效终点（TTSTAND），与 CINRG DNHS 对照组相比，viltolarsen 治疗的患者在最初两年内稳定了运动功能，随后两年内疾病进展明显放缓。viltolarsen 耐受性良好，大多数报告的治疗相关不良事件为轻度或中度。在研究期间没有参与者停止用药。
基于这项 4 年的 LTE 研究结果，viltolarsen 可能是适合外显子 53 跳跃的 DMD 患者的重要治疗策略。
