Abstract Details

Title Outcomes in Patients with Spinal Muscular Atrophy and Four or More SMN2 Copies Treated with Onasemnogene Abeparvovec: Findings from RESTORE

Topic Child Neurology and Developmental Neurology

Presentation(s) P7 - Poster Session 7 (8:00 AM-9:00 AM)

Poster/Presentation
Number 4-007

Objective We sought to describe clinical outcomes after onasemnogene abeparvovec (OA) monotherapy for patients with ≥4 SMN2 copies in RESTORE, a comprehensive, noninterventional spinal muscular atrophy (SMA) registry.

Background OA is a one-time gene replacement therapy for SMA. While clinical trials of OA included patients with two or three SMN2 gene copies, patients with ≥4 copies may be treated in clinical practice. Natural history and outcomes following SMA treatment have not been well-characterized for these patients.

Design/Methods We evaluated baseline characteristics, and post-treatment motor function, motor milestone achievement, use of ventilatory/nutritional support, and adverse events (AEs) (as of May 23, 2022, data cut). Patients evaluable for motor function or milestone achievement had ≥2 assessments, with ≥1 after OA.

Results Nine children with four SMN2 copies and five with ≥4 copies were included. All 14 cases were identified by newborn screening in the United States and treated presymptomatically. Median age at OA administration was 3.5 (range, 1–11) months. All six children with evaluable motor milestone assessments achieved new milestones. All four children evaluable for CHOP INTEND maintained/achieved the maximum score of 64 points. One child was evaluable for HINE-2 and achieved a ≥2-point increase. One child was evaluable for HFMSE and achieved a ≥3-point increase. Six children with recorded AE data had ≥1 treatment-emergent AE. Two children reported AEs ≥Grade 3 (one had otitis media and one with history of fetal stroke had seizure ~3.5 months post-OA). No deaths or use of ventilatory/nutritional support were reported.

Conclusions Patients with ≥4 SMN2 gene copies attained improvements in motor function and achieved new milestones after treatment with OA. SMA presentation with ≥4 SMN2 copies is heterogeneous, and laboratory determination of SMN2 copy number may be unreliable, highlighting the importance of early identification and intervention to optimize outcomes for all SMA patients.

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.
Kamal Benguerba	Kamal Benguerba has received personal compensation for serving as an employee of Novartis Gene Therapies. Kamal Benguerba has stock in Novartis Gene Therapies.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Nicole LaMarca	Ms. LaMarca has received personal compensation for serving as an employee of Novartis Gene Therapies.
Laurent Servais (John Radcliffe Hospital)	Laurent Servais has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Laurent Servais has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Laurent Servais has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Laurent Servais has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas. Laurent Servais has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer. Laurent Servais has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sarepta. The institution of Laurent Servais has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Evox. Laurent Servais has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PTC. Laurent Servais has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sysnav. Laurent Servais has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BioHaven. Laurent Servais has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dyne. Laurent Servais has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zentech. Laurent Servais has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MitoRx. Laurent Servais has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lupin. Laurent Servais has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Fibrogen. Laurent Servais has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alltrana. Laurent Servais has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Illumina. Laurent Servais 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. The institution of Laurent Servais has received research support from Roche. The institution of Laurent Servais has received research support from Novartis. The institution of Laurent Servais has received research support from Biogen. The institution of Laurent Servais has received research support from Zentech. The institution of Laurent Servais has received research support from BioHaven. The institution of Laurent Servais has received research support from PerkinHalmers. The institution of Laurent Servais has received research support from Scholar Rock.

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