Nusinersen in Infantile-onset Spinal Muscular Atrophy: Results from Longer-term Treatment from the Open-label SHINE Extension Study
Diana Castro1, Richard S. Finkel2, Michelle A. Farrar3, Mar Tulinius4, Kristin J. Krosschell5, Kayoko Saito6, Giulia Gambino7, Richard Foster7, Ishir Bhan7, Janice Wong7, Boris Kandinov7, Wildon Farwell7
1University of Texas Southwestern Medical Center, 2Nemours Children's Hospital, 3Sydney Children’s Hospital and University of New South Wales Sydney, 4Gothenburg University, 5Northwestern University, 6Tokyo Women’s Medical University, 7Biogen
Objective:
To present interim results from the SHINE open-label extension study (NCT02594124) for participants with infantile-onset SMA who transitioned from previous nusinersen trials.
Background:
Several clinical trials have demonstrated a favorable benefit:risk profile for nusinersen and established clinically meaningful efficacy on motor function.
Design/Methods:
Participants from CS3A, ENDEAR and EMBRACE could transition to SHINE. Following protocol amendment, all are receiving the Modified Maintenance Dosing Regimen (MMDR; 12mg nusinersen every 4 months). Previous ENDEAR participants initiated the MMDR at the end of the SHINE blinded loading dose period or 120 days after date of last loading period dose. Participants from CS3A and EMBRACE directly entered the MMDR period or if already participating in SHINE transitioned to the MMDR at their next study visit. Endpoints will be assessed from MMDR Day 1. 
Results:
65 participants from the ENDEAR nusinersen-treated and 24 from the sham-procedure group transitioned to SHINE. Based on the 15 October 2018 data cut, 21/59 (36%) participants who received nusinersen in ENDEAR/SHINE achieved the World Health Organization motor milestone of sitting without support, 5 (8%) achieved standing with assistance, and 3 (5%) walking with assistance at MMDR Day 1. None of those randomized to sham-procedure in ENDEAR and nusinersen in SHINE (n=22) achieved these milestones. Mean (±SD) Hammersmith Functional Motor Scale–Expanded score at MMDR Day 1 was 7.3 (6.82) for participants who received nusinersen in ENDEAR/SHINE (n=50) and 0 for participants randomized to sham-procedure in ENDEAR/nusinersen in SHINE (n=17). Data from the 2019 SHINE data cut for this cohort and participants who transitioned from the CS3A and EMBRACE studies, as well as an updated safety profile, will be presented.
Conclusions:

Continued analysis of SHINE study data will increase the information available on the long-term safety/tolerability and efficacy of repeated nusinersen doses in patients with infantile-onset SMA.

Study Supported by: Biogen