P.352Interim report on the safety and efficacy of longer-term treatment with nusinersen in later-onset spinal muscular atrophy (SMA): results from the SHINE study

Abstract

Nusinersen is the first approved treatment for SMA. Several clinical trials demonstrated a favorable benefit-to-risk profile and established clinically meaningful efficacy on motor function across a broad spectrum of SMA populations; a significant effect on event-free survival was observed in infantile-onset SMA. Our objective is to present baseline and interim results from the SHINE study (NCT02594124) for participants with later-onset SMA (most likely to develop Type II or III SMA) who transitioned from CHERISH. SHINE is an open-label extension for previous nusinersen study participants. Safety/tolerability is the primary endpoint; secondary endpoints include achievement of WHO motor milestones, Hammersmith Functional Motor Scale - Expanded (HFMSE), and Revised Upper Limb Module. These integrated analyses focus on children treated with nusinersen or sham control in CHERISH who transitioned to SHINE. In CHERISH, 84 participants received nusinersen and 83 transitioned to SHINE; all 42 participants in the sham control group transitioned. Baseline data are presented for 3 groups: previous sham control (CHERISH data; n=42); previous sham control/SHINE data (n=42); previous nusinersen in CHERISH/SHINE data (n=84). Median (range) age at first dose/sham procedure was 43.3 (25-90), 58.2 (40-107) and 49.7 (25-111) months, and median age at symptom onset was 11.0 (6-20), 11.0 (6-20), and 10.0 (6-20) months; 50%, 50% and 55% were female, respectively. Mean baseline (SD) WHO motor milestones was 1.5 (1.02), 1.4 (1.11) and 1.4 (0.96); mean (SD) HFMSE score was 19.9 (7.23), 19.8 (8.39), and 22.4 (8.33), in the 3 groups respectively. Results from an interim analysis with a 15 October 2018 data cutoff will be presented. Continued analysis of data from children treated with nusinersen via the SHINE study will increase the information available on the long-term safety/tolerability and efficacy of repeated nusinersen doses.