Abstract Details

Title Baseline Characteristics and Initial Safety Results in RESPOND: A Phase 4 Study of Nusinersen in Children with Spinal Muscular Atrophy (SMA) Who Received Onasemnogene Abeparvovec

Topic Child Neurology and Developmental Neurology

Presentation(s) P18 - Poster Session 18 (5:30 PM-6:30 PM)

Poster/Presentation
Number 6-003

Background OA is an adeno-associated viral (AAV) vector gene therapy for SMA in children age <2y. Preclinical studies demonstrated incomplete transduction of neurons by the AAV9 vector. Nusinersen has the potential to increase SMN protein in untransduced motor neurons.

Objective

To provide baseline characteristics of participants and initial safety findings in RESPOND (NCT04488133), an ongoing, single-arm study evaluating nusinersen treatment in children with SMA previously treated with onasemnogene abeparvovec (OA).

Design/Methods In RESPOND, children ≤36 months old who have ≥1 SMN2 copy, are nusinersen-naïve, and had suboptimal clinical response to OA administered ≥3 months previously, receive the approved 12mg nusinersen regimen of 4 loading doses followed by maintenance doses every 4 months. Suboptimal clinical response (investigator-determined) includes ≥1 of the following domains: motor function, respiratory support, swallowing/feeding ability, and other. Study recruitment is ongoing.

Results

As of 16 August 2021, 9 children (median [range] age 16.4 [5–30] months) were enrolled; 1 discontinued (parent/guardian decision). Most (8/9) had 2 SMN2 copies. Baseline mean±SD Hammersmith Infant Neurological Examination (HINE)-2 total score was 8.1±5.3. At baseline, all participants demonstrated suboptimal clinical status in ≥2 domains; motor and respiratory function were most common. Median duration on nusinersen and safety follow-up period was 64 days (range: 1–183 days). Most common adverse events (AEs) were infections (4 participants, 7 events [ear infection, viral gastroenteritis, parainfluenza virus infection (PIV), pneumonia, upper respiratory tract infection (URTI), viral URTI]) and vomiting (2 participants). Two participants had serious AEs: PIV (2 events in 1 participant) and URTI. No deaths or post-lumbar puncture syndrome events occurred. Additional results will be presented.

Conclusions Baseline characteristics of children in RESPOND showed suboptimal clinical status in multiple domains including motor and respiratory functions despite OA treatment. Initial safety findings indicate no AEs or serious AEs were considered related to nusinersen.

Authors/Disclosures
John Brandsema, MD (Children's Hospital of Philadelphia, Division of Neurology) PRESENTER	Dr. Brandsema has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Brandsema has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Brandsema has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for PTC Therapeutics. Dr. Brandsema has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sarepta. Dr. Brandsema has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Brandsema has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Argenx. Dr. Brandsema has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Janssen. Dr. Brandsema has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dyne. Dr. Brandsema has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Fibrogen. Dr. Brandsema has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. Dr. Brandsema has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Edgewise. The institution of Dr. Brandsema has received research support from Novartis. The institution of Dr. Brandsema has received research support from Biogen. The institution of Dr. Brandsema has received research support from Alexion. The institution of Dr. Brandsema has received research support from CSL Behring. The institution of Dr. Brandsema has received research support from Pfizer. The institution of Dr. Brandsema has received research support from PTC Therapeutics. The institution of Dr. Brandsema has received research support from Sarepta. The institution of an immediate family member of Dr. Brandsema has received research support from Argenx. The institution of Dr. Brandsema has received research support from Astellas. The institution of Dr. Brandsema has received research support from Fibrogen. The institution of Dr. Brandsema has received research support from Genentech. The institution of Dr. Brandsema has received research support from Janssen. The institution of Dr. Brandsema has received research support from Scholar Rock.
Julie A. Parsons, MD (Children's Hospital Colorado)	Dr. Parsons has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Parsons has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pfizer. Dr. Parsons has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Parsons has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ultragenex. The institution of Dr. Parsons has received research support from AveXis. The institution of Dr. Parsons has received research support from Biogen. The institution of Dr. Parsons has received research support from Scholar Rock. The institution of Dr. Parsons has received research support from Biohaven. The institution of Dr. Parsons has received research support from PTC Therapeutics. The institution of Dr. Parsons has received research support from Novartis.
Craig McDonald, MD (UC Davis Dept. of PM&R)	Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sarepta Therapeutics. Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for PTC Therapeutics. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas. Dr. McDonald has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Capricor Therapeutics. Dr. McDonald has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Catabasis. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Epirium Bio. Dr. McDonald has received personal compensation in the range of $0-$499 for serving as a Consultant for Italfarmaco. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Santhera Pharmaceuticals. Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta Therapeutics. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PTC Therapeutics. Dr. McDonald 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. McDonald has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Catabasis Pharmaceuticals. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Santhera Pharmaceuticals. The institution of Dr. McDonald has received research support from Sarepta Therapeutics. The institution of Dr. McDonald has received research support from PTC Therapeutics. The institution of Dr. McDonald has received research support from Santhera Pharmaceuticals. The institution of Dr. McDonald has received research support from Astellas. The institution of Dr. McDonald has received research support from Capricor Therapeutics. The institution of Dr. McDonald has received research support from Catabasis. The institution of Dr. McDonald has received research support from Epirium Bio. The institution of Dr. McDonald has received research support from Italfarmaco. Dr. McDonald has received research support from NS Pharma. The institution of Dr. McDonald has received research support from Pfizer. The institution of Dr. McDonald has received research support from NIH (NINDS). The institution of Dr. McDonald has received research support from NIDILRR. The institution of Dr. McDonald has received research support from Department of Defense. The institution of Dr. McDonald has received research support from Parent Project Muscular Dystrophy. The institution of Dr. McDonald has received research support from Muscular Dystrophy Association. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving as a Member National Advisory Board for Medical Rehabilitation Research with NIH.
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.
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.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Angela Paradis	Angela Paradis has received personal compensation for serving as an employee of Biogen. An immediate family member of Angela Paradis has received personal compensation for serving as an employee of Biogen. Angela Paradis has received stock or an ownership interest from Biogen. An immediate family member of Angela Paradis has received stock or an ownership interest from Biogen.
	No disclosure on file
Joanne M. Wagner, PhD, PT	Dr. Wagner has received personal compensation for serving as an employee of Xenon Pharmaceuticals. Dr. Wagner has received personal compensation for serving as an employee of Biogen. Dr. Wagner has stock in Biogen. Dr. Wagner has stock in Xenon Pharmaceuticals.
Kathleen C. Somera-Molina, PhD	Dr. Somera-Molina has received personal compensation for serving as an employee of Biogen. Dr. Somera-Molina has received stock or an ownership interest from Biogen.