Long-Term Functional Efficacy and Safety of Viltolarsen in Patients with Duchenne Muscular Dystrophy.
Long-Term Functional Efficacy and Safety of Viltolarsen in Patients with Duchenne Muscular Dystrophy.
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DOI：
10.3233/jnd-220811
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发表时间：
2022
影响因子：
3.3
通讯作者：
Hoffman, Eric P.
中科院分区：
文献类型：
--
作者：
Clemens, Paula R.;Rao, Vamshi K.;Connolly, Anne M.;Harper, Amy D.;Mah, Jean K.;McDonald, Craig M.;Smith, Edward C.;Zaidman, Craig M.;Nakagawa, Tomoyuki;Hoffman, Eric P.
Duchenne肌营养不良症(DMD)是一种罕见的遗传性疾病，其原因是DMD基因突变导致缺乏功能性肌营养不良蛋白。Viltolarsen是一种外显子53跳过疗法，已被证明可以增加内源性dystrophin水平。在这里，维托拉森治疗的患者的长期(两年)功能结果与匹配的历史对照组进行了比较。目的：评价反义寡核苷酸维拉生治疗53号外显子跳跃治疗的DMD的远期疗效和安全性。这项试验(NCT03167255)是先前在北美发表的一项为期24周的试验(NCT02740972)的延伸，该试验检查了dystrophin水平、计时功能测试与匹配的历史对照组(国际神经肌肉合作研究组Duchenne自然史研究，CINRG DNHS)比较，以及对接受Viltolarsen治疗的4至 <； 10年(N = 16)患有DMD且可跳过外显子53的男孩的安全性。两组均接受糖皮质激素治疗。所有16名参与者都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。在接受维托拉森治疗的参与者中，从基线到第109周，从仰卧位站立时间和跑步/步行10米的时间表现出稳定，而历史对照组则表现出下降(多个时间点的统计学显着差异)。安全性与之前24周试验中观察到的相似，主要是温和的。没有发生与治疗相关的严重不良事件，也没有中止治疗。基于这些两年多的研究结果，Viltolarsen可以成为符合外显子53跳过的DMD患者的新治疗选择。
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.