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Abstract Details

Phase 1 Study of Intrathecal Administration of AVXS-101 Gene-Replacement Therapy (GRT) for Spinal Muscular Atrophy Type 2 (SMA2) (STRONG)
Child Neurology and Developmental Neurology
P1 - Poster Session 1 (5:30 PM-6:30 PM)
7-059
To describe STRONG, a multicenter, open-label, phase 1 study (NCT03381729) of the safety, tolerability, optimal dose, and efficacy of onasemnogene abeparvovec (AVXS-101) in patients with SMA2.
SMA is a rapidly progressing neurodegenerative disease causing loss of motor and respiratory function. The genetic root cause is bi-allelic deletion/mutation of the survival motor neuron 1 gene (SMN1). Disease severity is modified by SMN2 copy number. AVXS-101 comprises an adeno-associated virus serotype 9-encapsulated transcript of human SMN that crosses the blood-brain barrier. In a phase 1 study (NCT02122952) in patients with SMA1, intravenous AVXS-101 demonstrated unprecedented improvements in survival, motor function, and motor milestone achievement
 
In STRONG, SMA2 patients (bi-allelic SMN1 mutations/deletions, 3 copies of SMN2) who could sit but not stand or walk independently were enrolled in 2 cohorts by age (cohort 1: ≥6 to <24 months; cohort 2: ≥24 to <60 months), received one-time intrathecal AVXS-101 at the highest acceptably safe dose, and were followed for 12 months. Three patients in cohort 1 received dose A. Based on demonstrated acceptable safety, three additional patients in cohort 2 received dose B. Given ongoing demonstration of acceptable safety, 13 additional patients in cohort 1 and 9 in cohort 2 were treated with dose B. Primary endpoints were safety/tolerability, optimal dose, ability to stand unsupported ≥3 sec (cohort 1), and Hammersmith Functional Motor Scale-Expanded score (cohort 2).
As of October 12, 2018, 28 patients have been enrolled at 11 sites. Enrollment is complete. To date, no safety or tolerability concerns have been identified. A study update will be provided.
Results from STRONG show intrathecal delivery of AVXS-101 in infants is feasible and well tolerated, with no safety concerns to date, and may support AVXS-101 as a promising treatment option for patients with SMA2.
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.
John W. Day, MD, PhD (Stanford University School of Medicine) Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis Gene Therapy. Dr. Day 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. Day has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Day 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. Day has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avidity. Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PepGen. Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Epirium Bio. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Solid Biosciences. Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Muscular Dystrophy Association. The institution of Dr. Day has received research support from Astellas Pharma. The institution of Dr. Day has received research support from Novartis Gene Therapy. The institution of Dr. Day has received research support from Biogen. The institution of Dr. Day has received research support from Roche/Genentech. The institution of Dr. Day has received research support from Sanofi/Genzyme. The institution of Dr. Day has received research support from Sarepta. The institution of Dr. Day has received research support from Scholar Rock. The institution of Dr. Day has received research support from AMO Pharma. The institution of Dr. Day has received research support from AnnJi. Dr. Day has received research support from CureSMA. The institution of Dr. Day has received research support from Muscular Dystrophy Association. The institution of Dr. Day has received research support from Ionis Pharmaceuticals. The institution of Dr. Day has received research support from NMD Pharma. The institution of Dr. Day has received research support from SMA Foundation. Dr. Day has received intellectual property interests from a discovery or technology relating to health care.
Basil T. Darras, MD (Children'S Hosp Boston Harvard Med School) The institution of Dr. Darras has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amicus. Dr. Darras has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Amicus. The institution of Dr. Darras has received research support from National Institutes of Health/National Institute of Neurological Disorders and Stroke,. The institution of Dr. Darras has received research support from Slaney Family Fund for SMA. The institution of Dr. Darras has received research support from Spinal Muscular Atrophy Foundation. The institution of Dr. Darras has received research support from CureSMA. The institution of Dr. Darras has received research support from Working on Walking Fund . The institution of Dr. Darras has received research support from CHERISH, CS2/CS12 . The institution of Dr. Darras has received research support from Biogen for CS11. The institution of Dr. Darras has received research support from AveXis. The institution of Dr. Darras has received research support from Sarepta Pharmaceuticals. The institution of Dr. Darras has received research support from PTC Therapeutics. The institution of Dr. Darras has received research support from Roche. The institution of Dr. Darras has received research support from Santhera. The institution of Dr. Darras has received research support from Scholar Rock. The institution of Dr. Darras has received research support from Fibrogen. The institution of Dr. Darras has received research support from Summit. Dr. Darras has received publishing royalties from a publication relating to health care. Dr. Darras has received publishing royalties from a publication relating to health care.
Nancy L. Kuntz, MD, FAAN (Ann & Robert H Lurie Children'S Hospital of Chicago) 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.
Anne M. Connolly, MD, FAAN (Nationwide Children's Hospital) Dr. Connolly has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Edgewise Therapeutics. Dr. Connolly has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Octapharma. Dr. Connolly has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. Dr. Connolly has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avidity. The institution of Dr. Connolly has received research support from Muscular Dystrophy Association. The institution of Dr. Connolly has received research support from NIH.
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.
Russell Butterfield, MD, PhD, BS (University of Utah) Dr. Butterfield has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. Dr. Butterfield 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. Butterfield has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Reata. The institution of Dr. Butterfield has received research support from NIH. The institution of Dr. Butterfield has received research support from Ionis. The institution of Dr. Butterfield has received research support from CDC.
Perry Shieh, MD, PhD, FAAN (UCLA) Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sarepta. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Argenx. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for CSL Behring. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Grifols. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Alexion. Dr. Shieh has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Biogen. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Genentech. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Argenx. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Catalyst.
Gihan Tennekoon, MD (Children's Hosp of Philadelphi) No disclosure on file
Susan T. Iannaccone, MD, FAAN (Department of Pediatrics) Dr. Iannaccone has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AveXis. Dr. Iannaccone has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Iannaccone has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sarepta. Dr. Iannaccone has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AveXis. Dr. Iannaccone 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. Iannaccone has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Catabasis. The institution of Dr. Iannaccone has received research support from AveXis. The institution of Dr. Iannaccone has received research support from Biogen. The institution of Dr. Iannaccone has received research support from Sarepta. The institution of Dr. Iannaccone has received research support from PTC Therapeutics. The institution of Dr. Iannaccone has received research support from FibroGen. The institution of Dr. Iannaccone has received research support from ReveraGen. The institution of Dr. Iannaccone has received research support from MDA. The institution of Dr. Iannaccone has received research support from PPMD. The institution of Dr. Iannaccone has received research support from NIH. Dr. Iannaccone has received personal compensation in the range of $0-$499 for serving as a grant reviewer with NIH.
Matthew N. Meriggioli, MD, FAAN (Novartis Biomedical Research) Dr. Meriggioli has received personal compensation for serving as an employee of Novartis Gene Therapies. Dr. Meriggioli has received stock or an ownership interest from Novartis.
Sidney A. Spector, MD, PhD (Harding Ave) No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Douglas Feltner No disclosure on file
Jerry R. Mendell, MD, FAAN (The Research Institute at Nationwide Children's Hospital) Dr. Mendell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vertex. Dr. Mendell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Mendell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sarepta Therapeutics . The institution of Dr. Mendell has received research support from Sarepta.