SMA – THERAPY: P.266 Nusinersen in infantile-onset spinal muscular atrophy: results from longer-term treatment from the open-label SHINE extension study

Abstract

We present results from the SHINE open-label extension study (NCT02594124) 27 August 2019 interim data cut for participants with infantile-onset SMA. Following protocol amendment all are receiving the Modified Maintenance Dosing Regimen (MMDR; 12 mg nusinersen every 4 months). Endpoints were assessed from MMDR Day 1. These analyses focus on participants with MMDR Day 1 data: 60 treated with nusinersen in ENDEAR/SHINE, and 22 with sham-procedure in ENDEAR/nusinersen in SHINE. Median (range) age at MMDR Day 1 was 2.57 (1.7–3.8) y for those treated with nusinersen in ENDEAR/SHINE, and 2.69 (1.8–3.7) y for those treated with sham-procedure in ENDEAR/nusinersen in SHINE. Median (range) time on study from first nusinersen dose to MMDR Day 1 was 2.08 (1.3–3.4) and 1.34 (0.5–1.9) y for these two groups. Mean (±SD) CHOP INTEND scores were 27.84 (8.09; n=60) at ENDEAR baseline, 44.6 (11.33; n=59) at MMDR Day 1, and 45.8 (13.27; n=56) at MMDR Day 480 for participants treated with nusinersen in ENDEAR/SHINE, and 29.59 (7.97; n=22) at ENDEAR baseline, 22.5 (10.07; n=22) at MMDR Day 1, and 24.5 (12.33; n=20) at MMDR Day 480 for those treated with sham-procedure in ENDEAR/nusinersen in SHINE. The WHO motor milestones of sitting unassisted, standing with assistance, and walking with assistance were achieved by 22/59 (37%), 5/59 (8%), and 3/59 (5%), respectively, of participants treated with nusinersen in ENDEAR/SHINE at MMDR Day 1, and 37/58 (64%), 11/58 (19%), and 4/58 (7%), respectively, at MMDR Day 480. None of those treated with sham-procedure in ENDEAR/nusinersen in SHINE (n=22) had achieved these milestones at MMDR Day 1; 1/20 (5%) was sitting without support at MMDR Day 480. Results for participants who transitioned from CS3A and EMBRACE and an updated safety profile will be presented. Continued analysis of SHINE data will increase the information available on the long-term safety/tolerability and efficacy of repeated nusinersen doses in patients with infantile-onset SMA.