Abstract Details

Title 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

Topic Child Neurology and Developmental Neurology

Presentation(s) P1 - Poster Session 1 (5:30 PM-6:30 PM)

Poster/Presentation
Number 7-063

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.

Authors/Disclosures
Basil T. Darras, MD (Children'S Hosp Boston Harvard Med School) PRESENTER	The institution of Dr. Darras has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amicus. Dr. Darras has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Amicus. The institution of Dr. Darras has received research support from National Institutes of Health/National Institute of Neurological Disorders and Stroke,. The institution of Dr. Darras has received research support from Slaney Family Fund for SMA. The institution of Dr. Darras has received research support from Spinal Muscular Atrophy Foundation. The institution of Dr. Darras has received research support from CureSMA. The institution of Dr. Darras has received research support from Working on Walking Fund . The institution of Dr. Darras has received research support from CHERISH, CS2/CS12 . The institution of Dr. Darras has received research support from Biogen for CS11. The institution of Dr. Darras has received research support from AveXis. The institution of Dr. Darras has received research support from Sarepta Pharmaceuticals. The institution of Dr. Darras has received research support from PTC Therapeutics. The institution of Dr. Darras has received research support from Roche. The institution of Dr. Darras has received research support from Santhera. The institution of Dr. Darras has received research support from Scholar Rock. The institution of Dr. Darras has received research support from Fibrogen. The institution of Dr. Darras has received research support from Summit. Dr. Darras has received publishing royalties from a publication relating to health care. Dr. Darras has received publishing royalties from a publication relating to health care.
Michelle A. Farrar	Michelle A. Farrar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Michelle A. Farrar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Michelle A. Farrar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Michelle A. Farrar has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Michelle A. Farrar has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche.
	No disclosure on file
Claudia A. Chiriboga, MD, FAAN (Columbia University)	Dr. Chiriboga has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentec. Dr. Chiriboga has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. The institution of Dr. Chiriboga has received research support from Roche. The institution of Dr. Chiriboga has received research support from Avexis/Novartis. The institution of Dr. Chiriboga has received research support from Biogen. The institution of Dr. Chiriboga has received research support from NIH. The institution of Dr. Chiriboga has received research support from Biohaven. The institution of Dr. Chiriboga has received research support from Genentec. Dr. Chiriboga has received publishing royalties from a publication relating to health care.
	No disclosure on file
Nancy L. Kuntz, MD, FAAN (Ann & Robert H Lurie Children'S Hospital of Chicago)	Dr. Kuntz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. Dr. Kuntz has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenyx. Dr. Kuntz has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Audentes Therapeutics. Dr. Kuntz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Kuntz has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. Dr. Kuntz has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Catalyst. Dr. Kuntz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Scholar Rock. The institution of Dr. Kuntz has received research support from Argenx. The institution of Dr. Kuntz has received research support from Astellas. The institution of Dr. Kuntz has received research support from Biogen. The institution of Dr. Kuntz has received research support from Catalyst. The institution of Dr. Kuntz has received research support from Genentech. The institution of Dr. Kuntz has received research support from Scholar Rock. The institution of Dr. Kuntz has received research support from Regenx-Bio. The institution of Dr. Kuntz has received research support from Solid Biosciences. The institution of Dr. Kuntz has received research support from AMO. The institution of Dr. Kuntz has received research support from Novartis. The institution of Dr. Kuntz has received research support from BioHaven. Dr. Kuntz has received personal compensation in the range of $50,000-$99,999 for serving as a Sarepta Express post gene therapy advisor with Sarepta.
Perry Shieh, MD, PhD, FAAN (UCLA)	Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sarepta. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Argenx. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for CSL Behring. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Grifols. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Alexion. Dr. Shieh has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Biogen. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Genentech. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Argenx. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Catalyst.
	No disclosure on file
Jacqueline Montes, PT, EdD, NCS (Columbia University Medical Center)	Ms. Montes has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Ms. Montes has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for F. Hoffman LaRoche. Ms. Montes has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Scholar Rock. Ms. Montes has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. The institution of Ms. Montes has received research support from NIH/NICHD. The institution of Ms. Montes has received research support from Muscular Dystrophy Association. The institution of Ms. Montes has received research support from Cure SMA.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Wildon Farwell, MD	Dr. Farwell has received personal compensation for serving as an employee of Dyne Therapeutics. Dr. Farwell has received personal compensation for serving as an employee of Satellos Biosciences. Dr. Farwell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Paragon Therapeutics. Dr. Farwell has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Stoke Therapeutics. Dr. Farwell has stock in Dyne Therapeutics. Dr. Farwell has stock in Satellos Bioscience.
Sandra P. Reyna, MD	Dr. Reyna has received personal compensation for serving as an employee of Novartis Gene Therapies.

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