Abstract Details

Title Baseline Characteristics and Interim Safety in RESPOND: A Phase 4 Study in Children with Spinal Muscular Atrophy (SMA) Treated With Nusinersen After Onasemnogene Abeparvovec

Topic Child Neurology and Developmental Neurology

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

Poster/Presentation
Number 4-003

Objective To provide baseline characteristics and interim safety findings in RESPOND (NCT04488133), a single-arm study evaluating nusinersen in children with SMA previously treated with onasemnogene abeparvovec (OA).

Background OA is an adeno-associated viral (AAV) vector gene therapy for SMA in children age <2 years. Animal models and limited human postmortem studies have demonstrated incomplete transduction of motor neurons by the AAV9 vector. Nusinersen has potential to increase SMN protein in untransduced motor neurons, which may provide additional clinical benefit to SMA patients.

Design/Methods

In RESPOND, children ≤36 months old with SMA and ≥1 SMN2 copy who are nusinersen-naïve and have suboptimal clinical status following OA administered ≥2 months previously, receive the approved 12-mg nusinersen regimen: 4 loading doses followed by maintenance doses every 4 months. Suboptimal clinical status (investigator-determined) includes ≥1 of these domains: motor function, respiratory support, swallowing/feeding ability, other. Recruitment is ongoing.

Results As of 15 August 2022, 34 children were enrolled and dosed. Median time from OA treatment to first nusinersen dose was 6.9 (range: 3–31) months. At baseline, 28/34 children demonstrated suboptimal clinical status in ≥2 domains after OA treatment; motor function (n=33) and respiratory function (n=22) were most common. Baseline mean±SD HINE-2 total score was 6.7±5.7 (n=33). Median duration on nusinersen was 183 (range: 1–540) days. Thirty of 34 participants had 2 SMN2 copies. AEs were typical of SMA; the most common were upper respiratory tract infection (n=6) and viral upper respiratory tract infection (n=5). Two participants had mild proteinuria considered nusinersen-related, which resolved. Nine participants had serious AEs; all were considered unrelated to nusinersen and resolved. No deaths or post-lumbar puncture syndrome events occurred. Additional data will be presented.

Conclusions In RESPOND, the majority of enrolled children had suboptimal clinical status in ≥2 domains at baseline after OA treatment. Interim safety findings were overall consistent with nusinersen’s safety profile.

Authors/Disclosures
Nancy L. Kuntz, MD, FAAN (Ann & Robert H Lurie Children'S Hospital of Chicago) PRESENTER	Dr. Kuntz 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. Kuntz has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenyx. Dr. Kuntz has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Audentes Therapeutics. Dr. Kuntz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Kuntz 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. Dr. Kuntz has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Catalyst. Dr. Kuntz 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. The institution of Dr. Kuntz has received research support from Argenx. The institution of Dr. Kuntz has received research support from Astellas. The institution of Dr. Kuntz has received research support from Biogen. The institution of Dr. Kuntz has received research support from Catalyst. The institution of Dr. Kuntz has received research support from Genentech. The institution of Dr. Kuntz has received research support from Scholar Rock. The institution of Dr. Kuntz has received research support from Regenx-Bio. The institution of Dr. Kuntz has received research support from Solid Biosciences. The institution of Dr. Kuntz has received research support from AMO. The institution of Dr. Kuntz has received research support from Novartis. The institution of Dr. Kuntz has received research support from BioHaven. Dr. Kuntz has received personal compensation in the range of $50,000-$99,999 for serving as a Sarepta Express post gene therapy advisor with Sarepta.
Julie A. Parsons, MD	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.
John Brandsema, MD (Children's Hospital of Philadelphia, Division of Neurology)	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 $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 as a Consultant for Scholar Rock. 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. Dr. Brandsema has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for CureSMA. 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 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.
Crystal M. Proud, MD (CSG Child & Adolescent Neurology)	Dr. Proud has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Avexis. Dr. Proud has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Proud has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sarepta. Dr. Proud has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Avexis. Dr. Proud has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. The institution of Dr. Proud has received research support from Biogen. The institution of Dr. Proud has received research support from Sarepta. The institution of Dr. Proud has received research support from Avexis. The institution of Dr. Proud has received research support from PTC. The institution of Dr. Proud has received research support from CSL Behring. The institution of Dr. Proud has received research support from Scholar Rock. The institution of Dr. Proud has received research support from Catabasis.
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
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.

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