Abstract Details

Title Longer-term Assessment of the Safety and Efficacy of Nusinersen for the Treatment of Infantile-onset Spinal Muscular Atrophy (SMA): An Interim Analysis of the SHINE Study

Topic Child Neurology and Developmental Neurology

Presentation(s) ES1 - (-)

Poster/Presentation
Number 003

Objective

Background Nusinersen is an antisense oligonucleotide approved for the treatment of SMA. It 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 time to death or permanent ventilation (EFS) in infantile-onset SMA.

Design/Methods SHINE is an open-label extension study for infants/children who participated in the ENDEAR, CHERISH, CS12 or CS3A nusinersen trials. Nusinersen doses were administered according to the regimen and participant’s cohort from the previous trial. Primary endpoint is safety/tolerability; secondary endpoints include achievement of HINE Section 2 motor milestones, and EFS.

Results The cutoff date was June 30, 2017; 89 patients transitioned from ENDEAR, 65/81 previously randomized to nusinersen and 24/41 to sham-control. Within SHINE only, 83 patients had an adverse event (AE). There were no treatment-related serious AEs. The most frequent AEs were pyrexia and upper respiratory tract infection. Mean (95% CI) change in HINE-2 total score from nusinersen initiation to last observed visit was 1.1 (0.20–1.90) for patients who received sham-control in ENDEAR and nusinersen in SHINE (n=20/24) and 5.8 (4.58–7.04) for those who received nusinersen in ENDEAR and SHINE (n=74/81; pooled ENDEAR/SHINE data). Median (95% CI) EFS time among patients treated with sham-control in ENDEAR was 22.6 (13.6–31.3) weeks versus 73.0 (36.3–NA) weeks among those who received nusinersen in ENDEAR and SHINE.

Conclusions Improvements in motor function and EFS continued among patients who initiated nusinersen in ENDEAR and motor function improved among those who initiated nusinersen in SHINE. Further analysis of SHINE data will provide additional information on the long-term safety/tolerability and efficacy of repeated nusinersen doses across multiple SMA populations.

Authors/Disclosures
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.
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.
	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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