Longer-term treatment with nusinersen: Results in later-onset spinal muscular atrophy from the SHINE study

Objective: To present results from the SHINE open-label extension study (NCT02594124) for participants with later-onset SMA. 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 CS2/12, CHERISH and EMBRACE could enroll in SHINE. Following protocol amendment, all participants transitioned to the Modified Maintenance Dosing Regimen (MMDR; 12mg nusinersen every 4 months). Participants initiated the MMDR at the end of the loading dose period or 120 days after date of last visit. Endpoints were assessed from MMDR Day 1. Results: 83 participants from the CHERISH nusinersen and 42 from the sham-procedure group transitioned to SHINE; 24 transitioned from CS2/12. Using the SHINE 15 October 2018 interim data cut, mean (±SD) Hammersmith Functional Motor Scale-Expanded (HFMSE) score at MMDR Day 1 (for participants with a MMDR Day 240 visit) was 26.0 (11.01) for those who received nusinersen in CHERISH/SHINE (n=61), and 21.2 (7.75) for those randomized to sham-procedure in CHERISH/nusinersen in SHINE (n=36). Mean (±SD) Revised Upper Limb Module (RULM) scores at MMDR Day 1 for these groups were 23.4 (5.54; n=61), and 21.2 (4.31; n=36), respectively. Mean (±SD) HFMSE at MMDR Day 1 (for participants with a MMDR Day 240 visit) was 33.2 (12.26) for those with SMA Type II who transitioned from CS2/12 (n=9) and 56.2 (6.85) for those with SMA Type III (n=13). Mean (±SD) RULM at MMDR Day 1 were 26.4 (4.81; Type II; n=8) and 36.7 (0.58; Type III; n=3), respectively. Data from the 2019 SHINE data cut for these cohorts and those who transitioned from EMBRACE, as well as an updated safety profile, will be presented. Conclusions: 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 later-onset SMA. Study Supported by: Biogen Disclosure: Dr. Chiriboga has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisory boards for SMA studies for AveXis, Biogen, Cytokinetics, Genentech, Ionis Pharmaceuticals, Inc., and Roche; educational speaker fees from Biogen.. Dr. Chiriboga has received research support from Grants from AveXis, Biogen, Ionis Pharmaceuticals, Inc., Roche, National Institutes of Health, and SMA Foundation.. 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. and Biogen, AveXis, Cytokinetics, Fibrogen, PTC Th. 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. Mercuri has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisory boards for SMA studies for AveXis, Biogen, Ionis Pharmaceuticals, Inc., Novartis, and Roche.. Dr. Mercuri has received research support from Principal Investigator for ongoing Biogen/Ionis Pharmaceuticals, Inc. and Roche clinical trials; support from Biogen for a natural history registry; funding from Famiglie SMA Italy, Italian Telethon, and SMA Europe.. Dr. Kirschner has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisory boards for SMA studies for AveXis, Biogen, Ionis Pharmaceuticals, Inc., Novartis, and Roche.. Dr. Kirschner has received research support from Research grant from Avexis, Biogen, PTC, Roche, Santhera, and Sarepta.. Dr. Kuntz has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisory boards for Argenyx, Audentes, AveXis, Biogen, Cytokinetics, PTC, Roche, and Sarepta.. Dr. Kuntz has received research support from Clinical trial research contracts with Audentes, AveXis, Biogen, Pfizer, Roche, and Sarepta.. Dr. Acsadi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AveXis, Biogen, Genentech, and Sarepta.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. Montes has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisory boards for Biogen, Cytokinetics, Roche, Scholar Rock, and SMA Foundation; consultant for Biogen and Ionis Pharmaceuticals, Inc.; research support from Eunice Kennedy Shriver National Institute for Child Health and Human Development and Muscular D. Dr. Montes has received research support from Research support from Eunice Kennedy Shriver National Institute for Child Health and Human Development and Muscular Dystrophy Association. 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.