Nusinersen in Infantile-onset Spinal Muscular Atrophy: Results from Longer-term Treatment from the Open-label SHINE Extension Study (1640)

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 Disclosure: Dr. Castro has nothing to disclose. Dr. Finkel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisor fees from Biogen and Ionis Pharmaceuticals, Inc. during ENDEAR and CHERISH; advisor to AveXis, Novartis, and Roche; data safety monitoring board for the AveXis AVX-101 Phase 1 gene transfer study and Roche Moonfish Phase 1b study; advisory capacit. Dr. Finkel has received compensation for serving on the Board of Directors of Royalty payments from Children9s Hospital of Philadelphia for licensing fees obtained for use of the CHOP INTEND motor function scale. Dr. Finkel has received royalty, license fees, or contractual rights payments from Royalty payments from Children9s Hospital of Philadelphia for licensing fees obtained for use of the CHOP INTEND motor function scale. Dr. Finkel has received research support from grants from Biogen and Ionis Pharmaceuticals, Inc. during ENDEAR and CHERISH; grants from AveXis, Cytokinetics, and Roche. Dr. Farrar has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisory board for AveXis, Biogen, and Roche. Dr. Farrar has received research support from Research grant from Biogen; Principal Investigator for ongoing AveXis, Roche and Biogen clinical trials. Dr. Tulinius has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisory boards for AveXis, Biogen, and PTC.. Dr. Tulinius has received research support from Principal investigator for Ionis Pharmaceuticals Inc./Biogen trials in Sweden.. Dr. Krosschell has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisory boards for Biogen and Roche; advisor/consultant for CureSMA; grant subcontracts to Lurie Children9s Hospital from AveXis, Biogen, Ionis Pharmaceuticals, Inc., and Scholar Rock.. Dr. Krosschell has received research support from Grant subcontracts to Lurie Children9s Hospital from AveXis, Biogen, Ionis Pharmaceuticals, Inc., and Scholar Rock.. Dr. Saito has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisory boards for Biogen, Roche/Chugai and Novartis Pharma; Consultant for AveXis.. Dr. Saito has received research support from Research funding from Biogen, Roche/Chugai and AveXis.. Dr. Gambino has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Gambino holds stock and/or stock options in Biogen. Dr. Foster has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities as an employee of Biogen. Dr. Foster holds stock and/or stock options in Holds stock/stock options in Biogen. Dr. Bhan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Bhan holds stock and/or stock options in Holds stock/stock options in Biogen. Dr. Wong has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Kandinov has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Kandinov holds stock and/or stock options in Holds stock/stock options in Biogen. Dr. Farwell has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Farwell holds stock and/or stock options in Biogen.