Abstract Details

Title Nusinersen in Infants Who Initiate Treatment in a Presymptomatic Stage of Spinal Muscular Atrophy (SMA): Interim Results From the Phase 2 NURTURE Study

Topic General Neurology

Presentation(s) S12 - General Neurology: Neurotherapeutics and Clinical Trials (5:18 PM-5:30 PM)

Poster/Presentation
Number 010

Objective To present interim results from the ongoing NURTURE study (NCT02386553) examining the efficacy and safety of intrathecal nusinersen initiated in presymptomatic infants with 2 or 3 SMN2 copies.

Background Nusinersen is the first approved treatment for SMA.

Design/Methods Enrolled infants were ≤6 weeks at first dose, clinically presymptomatic, and genetically diagnosed with SMA. The primary endpoint is time to death or respiratory intervention (≥6 hours/day continuously for ≥7 days or tracheostomy).

Results NURTURE has enrolled 25 infants (2 copies SMN2, n=15; 3 copies, n=10). As of 29 March 2019, the median age at last visit was 34.8 (range 25.7–45.4) months. All infants were alive and none required permanent ventilation. Median time to death or respiratory intervention could not be estimated because of too few events. Four infants (all with 2 SMN2 copies) required respiratory intervention for ≥6 hours/day continuously for ≥7 days, with all cases initiated during acute, reversible illness. All 25 infants achieved the WHO motor milestone sitting without support and 23/25 (92%) achieved walking with assistance; 22/25 (88%) were walking alone. Most children achieved these motor milestones (21/25 [84%] sitting without support, 15/23 [65%] walking with assistance, and 16/22 [73%] independent walking) within the 99^th percentile age window established by the WHO for healthy children. Nearly all children reached the maximum score on the CHOP INTEND scale. Phosphorylated neurofilament heavy chain (pNF-H) levels rapidly declined during the loading phase of nusinersen and then stabilized. Plasma pNF-H levels at Day 64 were significantly correlated with the WHO motor milestone walking alone age (r_s=0.64; p=0.0025; n=20). Additional pNF-H correlation analyses will be presented. No new safety concerns were identified.

Conclusions

These data demonstrate the continued benefit to infants who initiated nusinersen before symptom onset, emphasizing the value of newborn screening and early treatment.

Study Supported by: Biogen

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.
Kathryn J. Swoboda, MD	Dr. Swoboda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Swoboda has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. The institution of Dr. Swoboda has received research support from Biogen.
Enrico S. Bertini, MD (Bambino Gesu Hospital)	Dr. Bertini has received personal compensation for serving as an employee of Bambino Gesu' Children's Resesarch Hospital.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Stephanie Fradette	Stephanie Fradette has received personal compensation for serving as an employee of Biogen. Stephanie Fradette has stock in Biogen.
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.
Darryl C. De Vivo, MD, FAAN (Columbia University)	Dr. De Vivo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen and Novartis. Dr. De Vivo has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Aspa Therapeutics.

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