Abstract Details

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

Topic Child Neurology and Developmental Neurology

Presentation(s) S25 - Child Neurology: Spinal Muscular Atrophy: Treatments and Outcomes (1:00 PM-1:11 PM)

Poster/Presentation
Number 001

Objective To present interim results from the ongoing NURTURE study (NCT02386553) examining efficacy/safety of intrathecal nusinersen, initiated prior to symptom onset, in infants most likely to develop SMA Type I/II.

Background Nusinersen is the first approved treatment for SMA, supported by safety and meaningful efficacy in multiple clinical trials of affected populations across a broad spectrum of SMA severity.

Design/Methods

Enrolled infants were age ≤6 weeks at first dose, clinically presymptomatic, and genetically diagnosed with SMA with 2 or 3 SMN2 copies. The primary endpoint is time to death or respiratory intervention (≥6 hours/day continuously for ≥7 days or tracheostomy). The data cutoff date was May 15, 2018.

Results Twenty-five infants (2 copies SMN2, n=15; 3 copies, n=10) were enrolled. Median (range) age at last visit was 26.0 (14.0–34.3) months. All infants were alive and none required permanent ventilation including tracheostomy. Four infants (4/15 with 2 SMN2 copies; 0/10 with 3 SMN2 copies) required respiratory intervention, meeting the primary endpoint; all 4 initiated respiratory support during an acute, reversible illness. All (25/25) participants achieved the WHO motor milestone sitting without support and 22/25 (88%) achieved walking with assistance; 17/22 (77%) were walking alone. All infants had the ability to suck and swallow at their last observed visit. Plasma pNF-H levels rapidly declined during the loading phase of nusinersen and then stabilized. AEs were reported in all 25 infants; most (20/25; 80%) had AEs mild/moderate in severity; 9 had serious AEs. AEs of 6 infants were possibly related to study drug that resolved despite continued treatment, with the exception of one participant with proteinuria that was ongoing at data cutoff. No new safety concerns were identified.

Conclusions

These data demonstrate continued benefit to infants who initiated nusinersen in the presymptomatic stage of SMA and emphasize the value of early treatment.

Study support: Biogen

Authors/Disclosures
PRESENTER	No disclosure on file
Haluk Topaloglu, MD	No disclosure on file
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
Thomas O. Crawford, MD (Johns Hopkins Hospital)	Dr. Crawford has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen.
	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 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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