AVXS-101 (Onasemnogene Abeparvovec) for SMA 1: Comparative Study with a Prospective Natural History Cohort

被引：139

作者：

Al-Zaidy, Samiah A. ^{[1
,2
]}

Kolb, Stephen J. ^{[3
,4
]}

Lowes, Linda ^{[1
,2
]}

Alfano, Lindsay N. ^{[1
,2
]}

Shell, Richard ^{[2
]}

Church, Kathleen R. ^{[1
]}

Nagendran, Sukumar ^{[5
]}

Sproule, Douglas M. ^{[5
]}

Feltner, Douglas E. ^{[5
]}

Wells, Courtney ^{[5
]}

Ogrinc, Francis ^{[5
]}

Menier, Melissa ^{[5
]}

L'Italien, James ^{[5
]}

Arnold, W. David ^{[3
]}

Kissel, John T. ^{[2
]}

Kaspar, Brian K. ^{[5
]}

Mendell, Jerry R. ^{[1
,2
,3
]}

机构：

[1] Nationwide Childrens Hosp, Ctr Gene Therapy Res Inst, Columbus, OH 43205 USA

[2] Ohio State Univ, Dept Pediat, Wexner Med Ctr, Columbus, OH 43210 USA

[3] Ohio State Univ, Dept Neurol, Wexner Med Ctr, Columbus, OH 43210 USA

[4] Ohio State Univ, Dept Biol Chem & Pharmacol, Wexner Med Ctr, Columbus, OH 43210 USA

[5] AveXis Inc, Bannockburn, IL USA

来源：

JOURNAL OF NEUROMUSCULAR DISEASES | 2019年 / 6卷 / 03期

关键词：

Gene therapy; spinal muscular atrophy; natural history; neuromuscular diseases;

D O I：

10.3233/JND-190403

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

100204 [神经病学];

摘要：

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.

引用

页码：307 / 317

页数：11

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