Abstract Details

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

Topic General Neurology

Presentation(s) S12 - General Neurology: Neurotherapeutics and Clinical Trials (4:54 PM-5:06 PM)

Poster/Presentation
Number 008

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

Authors/Disclosures
Diana Castro, MD (Neurology Rare Disease Center) PRESENTER	Dr. Castro has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Castro has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Castro has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PTC. Dr. Castro 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. Castro has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Castro has received research support from Biogen. The institution of Dr. Castro has received research support from Sarepta. The institution of Dr. Castro has received research support from Fibrogen .
Richard S. Finkel, MD, FAAN (St. Jude Children's Research Hospital)	Dr. Finkel has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AveXis. Dr. Finkel 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. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Catabasis. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Capricor. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ReveraGen. Dr. Finkel has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Finkel 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. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. Finkel has received research support from AveXis. The institution of Dr. Finkel has received research support from Biogen. The institution of Dr. Finkel has received research support from Capricor. The institution of Dr. Finkel has received research support from Catabasis. The institution of Dr. Finkel has received research support from ReveraGen. The institution of Dr. Finkel has received research support from Roche. The institution of Dr. Finkel has received research support from Scholar Rock. Dr. Finkel has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Finkel has received intellectual property interests from a discovery or technology relating to health care. Dr. Finkel has received personal compensation in the range of $0-$499 for serving as a Speaker in workshop with National Academy of Sciences. Dr. Finkel has a non-compensated relationship as a advisor with n-Lorem Foundation that is relevant to AAN interests or activities. Dr. Finkel has a non-compensated relationship as a Board Member with EveryLife Foundation that is relevant to AAN interests or activities.
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
	No disclosure on file
Kayoko Saito	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Janice Wong, MD	Dr. Wong has received personal compensation for serving as an employee of Janssen Research & Development. Dr. Wong has received personal compensation for serving as an employee of Biogen. Dr. Wong has stock in Biogen. Dr. Wong has stock in Janssen Research & Development.
Boris Kandinov	No disclosure on file
Wildon Farwell, MD	Dr. Farwell has received personal compensation for serving as an employee of Biogen. Dr. Farwell has received stock or an ownership interest from Biogen.

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