One-Time Intrathecal (IT) Administration of AVXS-101 IT Gene-Replacement Therapy for Spinal Muscular Atrophy: Phase 1 Study (STRONG)

Objective: To assess the safety/tolerability, optimal dose, and efficacy of AVXS-101 IT in sitting but non-ambulatory patients with spinal muscular atrophy (SMA). Background: SMA is a rapidly progressing disease causing loss of motor/respiratory functions due to survival motor neuron 1 gene (SMN1) deletion/mutation. Disease severity is modified by SMN2 copy number. AVXS-101 IT is a gene-replacement therapy that addresses the genetic root cause of SMA. Design/Methods: In STRONG (phase 1 study; NCT03381729), SMA patients (biallelic SMN1 loss, 3xSMN2) aged ≥6– Results: As of 31 May 2019, 31 patients were enrolled (dose A, complete: n=3, ≥6– Conclusions: Interim data from STRONG demonstrates early signs of efficacy in sitting but non-ambulatory patients with SMA. Disclosure: Dr. Finkel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisor fees from Biogen and Ionis Pharmaceuticals, Inc. during ENDEAR and CHERISH; advisor to AveXis, Novartis, and Roche; data safety monitoring board for the AveXis AVX-101 Phase 1 gene transfer study and Roche Moonfish Phase 1b study; advisory capacit. Dr. Finkel has received compensation for serving on the Board of Directors of Royalty payments from Children’s Hospital of Philadelphia for licensing fees obtained for use of the CHOP INTEND motor function scale. Dr. Finkel has received royalty, license fees, or contractual rights payments from Royalty payments from Children’s Hospital of Philadelphia for licensing fees obtained for use of the CHOP INTEND motor function scale. Dr. Finkel has received research support from grants from Biogen and Ionis Pharmaceuticals, Inc. during ENDEAR and CHERISH; grants from AveXis, Cytokinetics, and Roche. Dr. Day has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consultant for AMO Pharma, AveXis, Biogen, Cytokinetics, Ionis Pharmaceuticals, Inc., Pfizer, Roche, Santhera, Sarepta.. Dr. Day has received royalty, license fees, or contractual rights payments from Patents licensed to Athena Diagnostics for genetic testing of myotonic dystrophy type 2 (US patent 7442782) and spinocerebellar ataxia type 5 (US patent 7527931). Dr. Day has received research support from Grants from AMO Pharma, aTyr, AveXis, Biogen, Bristol-Myers Squibb, Cytokinetics, Ionis Pharmaceuticals, Inc., Roche, Sanofi-Genzyme, Sarepta.. Dr. Darras has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AveXis, Biogen, Bristol-Myers Squibb, Cytokinetics, Marathon, PTC Therapeutics, Roche, Santhera, and Sarepta. Dr. Darras has received research support from the National Institutes of Health/National Institute of Neurological Disorders and Stroke, the Slaney Family Fund for SMA, Working on Walking Fund, the SMA Foundation; CureSMA, Ionis Pharmaceuticals, Inc. and Biogen, AveXis, Cytokinetics, Fibrogen, PTC Th. Dr. Kuntz has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisory boards for Argenyx, Audentes, AveXis, Biogen, Cytokinetics, PTC, Roche, and Sarepta.. Dr. Kuntz has received research support from Clinical trial research contracts with Audentes, AveXis, Biogen, Pfizer, Roche, and Sarepta.. Dr. Connolly has nothing to disclose. Dr. Crawford has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AveXis, Biogen, Catalyst, Cure SMA, Cytokinetics, Marathon, Muscular Dystrophy Association, Novartis, Roche, Sarepta, Scholar Rock, and the Spinal Muscular Atrophy Foundation. Dr. Butterfield has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Avexis, Pfizer. Dr. Butterfield has received research support from Pfizer, Avexis, Biogen, PTC Therapeutics, Acceleron, Catavasis Pharmaceuticals, and Sarepta Therapeutics. Dr. Shieh has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Audentes, Sarepta, Pfizer, Genentech, Avexis, Biogen, Catalyst, Argenyx, Alexion, CSL Behring, Grifols. Dr. Shieh has received research support from Sarepta, Pfizer, Audentes, Avexis, Biogen, PTC, Roche, Sanofi, Reveragen, Acceleron.Dr. Tennekoon has nothing to disclose. Dr. Iannaccone has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sarepta, Avexis. Catabasis, Genentech, Texas Neurological Society, American Academy of Pediatrics, and Methodist Hospitals of Memphis. Dr. Iannaccone has received research support from Avexis, Biogen, Mallinckrodt, PTC therapeutics, Sarepta, Regeneron, FibroGen, Scholar Rock, and Pfizer. Dr. Meriggioli has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of AveXis, Inc., a Novartis company, and may own Novartis stock or other equities. Dr. Tauscher-Wisniewski has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of AveXis, Inc., a Novartis company, and may own Novartis stock or other equities. Dr. Shoffner has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of AveXis, Inc., a Novartis company, and may own Novartis stock or other equities. Dr. Ogrinc has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of AveXis, Inc., a Novartis company, and may own Novartis stock or other equities. Dr. Kavanagh has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of AveXis, Inc., a Novartis company, and may own Novartis stock or other equities. Has received consulting fees from UCB Pharma, Colorado Prevention Center, Zosano Pharma, Pure Tech Health, DiaMedica, Karuna Therapeutics. Dr. Kernbauer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of AveXis, Inc., a Novartis company, and may own Novartis stock or other equities. Dr. Whittle has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of AveXis, Inc., a Novartis company, and may own Novartis stock or other equities. Dr. Sproule has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of AveXis, Inc., a Novartis company, and may own Novartis stock or other equities. Dr. Sproule has received compensation for serving on the Board of Directors of AveXis, a Novartis company. Dr. Feltner has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Acadia Pharmaceuticals, AveXis, Inc., Embera Neurotherapeutics. Dr. Feltner has received compensation for serving on the Board of Directors of Embera Neurotherapeutics. Dr. Feltner holds stock and/or stock options in AveXis, Inc. which sponsored research in which Dr. Feltner was involved as an investigator. Dr. Feltner holds stock and/or stock options in AveXis, Inc.. Dr. Mendell has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with For clinical trial consulting and serving on scientific advisory boards from AveXis, Inc.. Dr. Mendell has received research support from AveXis, Inc..