Interim Efficacy and Safety Results from the Phase 3 ENDEAR Study of Nusinersen in Infants Diagnosed with Spinal Muscular Atrophy (SMA)

作者：R. Finkel, N. Kuntz, Eugenio Mercuri, Francesco Muntoni, Claudia A. Chiriboga, Basil T. Darras, Haluk Topaloğlu, Jacqueline Montes, John Q. Su, Zhi-Qun Zhong, Sarah Gheuens, C. Frank Bennett, Eugene Schneider, Wildon Farwell · 发表于：Neuropediatrics · 年份：2017 · DOI：10.1055/s-0037-1602912 · 被引用次数：3 · 研究领域：Neurogenetic and Muscular Disorders Research、Fuel Cells and Related Materials

Background/Purpose: Nusinersen is an antisense oligonucleotide that modifies SMN2 pre-mRNA splicing. Interim results of the phase 3, randomized, double-blind, sham procedure-controlled ENDEAR study (NCT02193074) evaluating nusinersen in infants with SMA are reported. Methods: Symptomatic infants diagnosed with SMA (with clinical features consistent with Type 1 SMA) were randomized (2:1) to receive intrathecal nusinersen (12-mg scaled equivalent dose) or sham procedure. Key eligibility criteria included genetic diagnosis of SMA, 2 SMN2 gene copies, and age ≤7 months with no hypoxemia at screening. The interim analysis primary endpoint was the proportion of motor milestone responders using modified section 2 of the Hammersmith Infant Neurological Examination (HINE; defined as more HINE categories improving [≥2-point increase/maximal score in kicking ability, or ≥1-point increase in head control, rolling, sitting, crawling, standing, or walking] than worsening). A predefined interim efficacy analysis was conducted after approximately 80 participants were expected to complete Day 183 visit. Results: 80 and 41 patients were treated with nusinersen or sham procedure, respectively. Baseline demographics were similar except for age and geographic region. A significantly greater proportion of motor milestone responders was observed in nusinersen-treated versus control patients ( p < 0.0001). No adverse events (AEs) were considered related by the investigator; 11% of nusinersen-treated...