Interim Report on the Safety and Efficacy of Longer-term Treatment With Nusinersen in Later-onset Spinal Muscular Atrophy (SMA): Results From the SHINE Study (P1.6-063)

Objective: 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. Background: Nusinersen is the first approved treatment for SMA. Several clinical trials demonstrated a favorable benefit: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. Design/Methods: SHINE is an open-label extension for participants in previous nusinersen studies, with dosing every 120 days after protocol amendment; initially 180 days for CHERISH 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. Results: 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 an October 15, 2018 data cutoff will be presented. Conclusions: 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. Disclosure: Dr. Darras has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AveXis, Biogen, Bristol-Myers Squibb, Cytokinetics, Marathon, PTC Therapeutics, Roche, Santhera, and Sarepta. Dr. Darras has received research support from the National Institutes of Health/National Institute of Neurological Disorders and Stroke, the Slaney Family Fund for SMA, Working on Walking Fund, the SMA Foundation, CureSMA, Ionis Pharmaceuticals, Inc., Biogen, AveXis, Cytokinetics, Fibrogen, PTC Therapeutics, Roche, Santhera, Sarepta, and Summit. Dr. Farrar has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Scientific advisory board honoraria from Biogen. Dr. Farrar has received research support from Research support from Motor Neuron Diseases Research Institute of Australia, Biogen grant, principal investigator for ongoing Biogen and AveXis clinical trials. Dr. Mercuri has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with SMA studies for AveXis, Biogen, Ionis Pharmaceuticals, Inc., Novartis, and Roche. Dr. Mercuri has received research support from Ionis Pharmaceuticals, Inc./Biogen and Roche clinical trials, Famiglie SMA Italy, Italian Telethon, and SMA Europe. Dr. Chiriboga has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AveXis, Biogen, Genetech, Ionis Pharmaceuticals, Inc., and Roche. Dr. Chiriboga has received research support from AveXis, Biogen, Ionis Pharmaceuticals, Inc., the National Institute of Health, Roche, and the SMA Foundation. Dr. Kirschner has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AveXis, Biogen, Ionis Pharmaceuticals, Inc., Novartis, and Roche. Dr. Kirschner has received research support from Biogen, Roche, Santhera, and PTC Therapeutics. Dr. Kuntz has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Audentes, AveXis, Catalyst, Cytokinetics, Marathon, PTC Therapeutics, and Sarepta Therapeutics. Dr. Kuntz has received research support from AveXis, Audentes, Biogen, Pfizer, Roche and Sarepta Therapeutics. Dr. Shieh has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion, AveXis, Inc., Biogen, Grifols, PTC Therapeutics and Sarepta. Dr. Shieh has received research support from AveXis, Inc., Audentes, Biogen, Bristol-Myers Squibb, Cytokinetics, Catalyst, Fibrogen, Ionis Pharmaceuticals, Inc., Marathon, Pfizer, PTC Therapeutics, Sarepta, Santhera, Summit, Sanofi/Genzyme and Ultragenyx. Dr. Tulinius has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AveXis, Biogen, and PTC. Dr. Tulinius has received research support from Ionis Pharmaceuticals, Inc./Biogen trials in Sweden. Dr. Montes has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Astellas, Biogen, Cytokinetics, Roche, Scholar Rock, Ionis Pharmaceuticals, Inc and Biogen. Dr. Montes has received research support from MDA and NICHD / NIH. Dr. Gambino has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen Idec. Dr. Gambino holds stock and/or stock options in Biogen Idec. Dr. Foster has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Foster holds stock and/or stock options in Biogen. Dr. Bhan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Bhan holds stock and/or 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. Dr. Reyna has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Reyna holds stock and/or stock options in Biogen.