P.378 - Efficacy and safety of nusinersen in children with later-onset spinal muscular atrophy (SMA): end of study results from the phase 3 CHERISH study

Abstract

The efficacy and safety of nusinersen, an antisense oligonucleotide, in children with later-onset SMA was assessed in CHERISH, a phase 3, multicenter, randomized, double-blind, sham-procedure controlled study (NCT02292537). Children aged 2–12 years with onset of SMA clinical symptoms at age >6 months and confirmed 5q SMA were enrolled and randomized (2:1 intrathecal nusinersen 12 mg vs sham-control, stratified based on screening age <6 versus ≥6 years; 4 dosing events over 15 months). Primary endpoint: change from baseline to month 15 in the Hammersmith Functional Motor Scale–Expanded (HFMSE) total score. Secondary endpoints include: proportion of children achieving a ≥ 3-point increase from baseline in HFMSE score and achieving any new WHO motor milestones, and the change in revised Upper Limb Module (RULM) test score at month 15. Safety and tolerability were assessed. A pre-specified interim analysis of CHERISH was conducted on August 31, 2016 (n = 126). The least square mean (LSM) treatment difference (95% CI) in motor function assessed by mean HFMSE score at 15 months between the nusinersen and sham-control groups: 5.9 (3.7, 8.1) points; P = 0.0000002. 57.3% of nusinersen-treated vs 20.5% of sham-treated children had a ≥ 3 point increase in HFMSE score, and 17.1% vs 10.5% achieved new WHO motor milestones. The nusinersen group also showed greater improvement in RULM score vs the sham-control group: LSM treatment difference=3.4 points. A favorable safety profile, with no study or treatment discontinuations, consistent with other published results was demonstrated. At interim analysis, statistically and clinically significant improvements in motor function were observed in nusinersen- versus sham-treated children. Additional end of study results will be reported. Children from CHERISH and other trials of nusinersen are being transitioned into the SHINE (NCT02594124) open-label extension study.