AVXS-101 (Onasemnogene Abeparvovec) for SMA 1: Comparative Study with a Prospective Natural History Cohort
AVXS-101 (Onasemnogene Abeparvovec) for SMA 1: Comparative Study with a Prospective Natural History Cohort
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DOI：
10.3233/jnd-190403
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发表时间：
2019-01-01
影响因子：
3.3
通讯作者：
Mendell, Jerry R.
中科院分区：
文献类型：
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作者：
Al-Zaidy, Samiah A.;Kolb, Stephen J.;Mendell, Jerry R.
背景：1型脊髓性肌萎缩症（SMA1）是婴儿死亡的主要遗传原因，包括AVXS-101 （onasemnogene abeparvovec, Zolgensma (R)）基因替代疗法在内的治疗方法正在出现。目的：本研究评估AVXS-101在1型脊髓性肌萎缩症（SMA1）婴儿中的有效性，并与前瞻性自然史队列和健康婴儿队列进行比较。方法：12例SMA1患儿接受建议治疗剂量的AVXS-101 （NCT02122952）。在可能的情况下，将以下结果与参加NeuroNEXT （NN101）研究（NCT01736553）的SMA1婴儿（n = 16）和健康婴儿（n = 27）的自然史队列进行比较：无事件生存期、chop - tend评分、运动里程碑成就、复合肌肉动作电位（CMAP）和不良事件。结果：AVXS-101和NN101研究中SMA1婴儿的基线特征在年龄和遗传谱上相似。与NN101研究相比，avxs -101治疗的婴儿在随访24个月后存活的比例更高（分别为100%和38%）。NN101 SMA1婴儿的平均基线chop - intent评分为20.3，到24个月时恶化至5.3；avxs -101治疗婴儿的平均基线评分为28.2，到24个月时提高到56.5。接受AVXS-101治疗的婴儿达到了运动里程碑，如独立坐着和行走。avxs -101治疗的婴儿在6个月和24个月时CMAP峰面积有所改善（平均分别为1.1和3.2 mV/s）。结论：在本研究中，AVXS-101增加了SMA1婴儿的生存概率，迅速改善了运动功能，并使运动里程碑实现。
Background: Spinal muscular atrophy type 1 (SMA1) is the leading genetic cause of infant mortality for which therapies, including AVXS-101 (onasemnogene abeparvovec, Zolgensma (R)) gene replacement therapy, are emerging.Objective: This study evaluated the effectiveness of AVXS-101 in infants with spinal muscular atrophy type 1 (SMA1) compared with a prospective natural history cohort and a cohort of healthy infants.Methods: Twelve SMA1 infants received the proposed therapeutic dose of AVXS-101 (NCT02122952). Where possible, the following outcomes were compared with a natural history cohort of SMA1 infants (n = 16) and healthy infants (n = 27) enrolled in the NeuroNEXT (NN101) study (NCT01736553): event-free survival, CHOP-INTEND scores, motor milestone achievements, compound muscle action potential (CMAP), and adverse events.Results: Baseline characteristics of SMA1 infants in the AVXS-101 and NN101 studies were similar in age and genetic profile. The proportion of AVXS-101-treated infants who survived by 24 months of follow-up was higher compared with the NN101 study (100% vs 38%, respectively). The average baseline CHOP-INTEND score for NN101 SMA1 infants was 20.3, worsening to 5.3 by age 24 months; the average baseline score in AVXS-101-treated infants was 28.2, improving to 56.5 by age 24 months. Infants receiving AVXS-101 achieved motor milestones, such as sitting unassisted and walking. Improvements in CMAP peak area were observed in AVXS-101-treated infants at 6 and 24 months (means of 1.1 and 3.2 mV/s, respectively).Conclusions: In this study, AVXS-101 increased the probability of survival, rapidly improved motor function, and enabled motor milestone achievement in SMA1 infants.