Abstract Details

Title Interim Report on the Safety and Efficacy of Longer-Term Treatment With Nusinersen in Infantile-Onset Spinal Muscular Atrophy (SMA): Updated Results From the SHINE Study

Topic Child Neurology and Developmental Neurology

Presentation(s) S25 - Child Neurology: Spinal Muscular Atrophy: Treatments and Outcomes (1:33 PM-1:44 PM)

Poster/Presentation
Number 004

Background Nusinersen has demonstrated a favorable benefit:risk profile and shown significant and clinically meaningful efficacy on motor function across a broad spectrum of SMA populations and on event-free survival (EFS; time to death or permanent ventilation) in infantile-onset SMA. SHINE is an open-label extension study for infants/children who previously participated in nusinersen clinical trials.

Objective To report interim results from the SHINE study (NCT02594124) for individuals with infantile-onset SMA (most likely to develop Type I) who transitioned from ENDEAR.

Design/Methods Nusinersen doses were initially administered according to participant’s previous trial cohort/regimen. The primary endpoint is safety/tolerability; secondary endpoints include achievement of HINE-2 motor milestones and EFS.

Results The cutoff date for the previous interim analyses was June 30, 2017; 89 infants transitioned from ENDEAR, 65/81 were previously randomized to nusinersen and 24/41 to sham-control. Within SHINE only, 83 infants had an adverse event (AE). Infants who received sham-control in ENDEAR and nusinersen in SHINE (n=20/24) and those who received nusinersen in ENDEAR and SHINE (n=74/81; pooled ENDEAR/SHINE data) demonstrated continued improvements in HINE-2 total score from nusinersen initiation to last observed visit (mean [95%CI] change: 1.1 [0.20–1.90] and 5.8 [4.58–7.04], respectively). Median (95%CI) EFS time among sham-control infants in ENDEAR was 22.6 (13.6–31.3) weeks vs 73.0 (36.3–NA) weeks for those who received nusinersen in ENDEAR and SHINE. Results from an interim analysis with an October 15, 2018 cutoff date will be presented.

Conclusions At the time of the previous data cutoff, motor function and EFS continued to improve in infants who initiated nusinersen in ENDEAR and motor function stabilized or started to show improvement in those who initiated nusinersen in SHINE. Data from more recent analyses will provide additional information on the long-term efficacy and safety of nusinersen in infantile-onset SMA.

Authors/Disclosures
Richard S. Finkel, MD, FAAN (St. Jude Children's Research Hospital) PRESENTER	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.
Diana Castro, MD (Neurology Rare Disease Center)	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 .
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
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.
Sandra P. Reyna, MD	Dr. Reyna has received personal compensation for serving as an employee of Novartis Gene Therapies.

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