Onasemnogene Abeparvovec-xioi Gene-Replacement Therapy for Spinal Muscular Atrophy Type 1 (SMA1): Phase 3 US Study (STR1VE) Update (1828)

Objective: Evaluate preliminary data from the phase 3 STR1VE (NCT03306277) study investigating efficacy and safety of one-time intravenous infusion of onasemnogene abeparvovec-xioi (formerly AVXS-101) in patients with SMA1. Background: SMA1 is caused by functional loss of SMN1, and typically results in death/permanent ventilation by 2 years if untreated. Onasemnogene abeparvovec, a one-time, AAV9-based, intravenous gene-replacement therapy addresses the genetic root cause of SMA and is designed for immediate, sustained SMN protein expression in neurons. Design/Methods: STR1VE is a multicenter, open-label, single-arm, single-dose study in symptomatic SMA1 patients aged Results: As of 31 May 2019, enrollment is complete (N=22; 2xSMN2; 10 male, 12 female). Mean age (range) at dosing: 3.7 (0.5–5.9) months. Of 19 patients who could have reached age 13.6 months at data cutoff, 17 (89.5%) were surviving without permanent ventilation (death unrelated to treatment, n=1; respiratory endpoint/withdrawal of consent, n=1) compared with 25% survival in untreated natural history. Mean (range) baseline CHOP INTEND score was 32 (18–52) and increased 6.9, 11.7, and 14.3 points at months 1, 3, and 5, respectively. 11/22 (50%) infants sat independently ≥30 sec (mean of 8.2 months post-treatment); 5/6 (83%) patients ≥18 months old sat independently ≥30 sec (co-primary endpoint). As of 8 March 2019, treatment-emergent adverse events of special interest were transient and not associated with any sequelae. Conclusions: Interim data from the ongoing STR1VE study suggests that a one-time intravenous dose of onasemnogene abeparvovec provides benefit in patients with SMA1. Final data from STR1VE will be presented. Disclosure: 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. Chiriboga has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisory boards for SMA studies for AveXis, Biogen, Cytokinetics, Genentech, Ionis Pharmaceuticals, Inc., and Roche; educational speaker fees from Biogen.. Dr. Chiriboga has received research support from Grants from AveXis, Biogen, Ionis Pharmaceuticals, Inc., Roche, National Institutes of Health, and SMA Foundation.. 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. 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. 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. Connolly 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. 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. Pena has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AveXis, Inc.. Dr. Pena has received research support from AveXis, Inc., Biogen, Roivant, and Sanofi-Genzyme. 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. Smith has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with  Biogen, Sarepta, Pfizer, Biomarin. Dr. Smith has received research support from AveXis, Inc.. Dr. Schultz 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; prior advisory board participation from AveXis, Inc., and Biogen. Dr. Schultz has received research support from AveXis, Inc.. 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. 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. 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. Shah 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. Ouyang 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. Macek 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. 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. 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. 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..