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15.33 AVXS-101 in presymptomatic spinal muscular atrophy (SMA)
  1. Kevin A Strauss1,
  2. Kathryn J Swoboda2,
  3. Michelle A Farrar3,
  4. Hugh J McMillan4,
  5. Julie Parsons5,
  6. Jena M Krueger6,
  7. Susan T Iannaccone7,
  8. Claudia A Chiriboga8,
  9. Jennifer M Kwon9,
  10. Kayoko Saito10,
  11. Mariacristina Scoto11,
  12. Imran Kausar12,
  13. Meredith Schultz12,
  14. Elaine Kernbauer12,
  15. Marcia Farrow12,
  16. Francis G Ogrinc12,
  17. Sarah Kavanagh12,
  18. Douglas E Feltner12,
  19. Bryan E McGill12,
  20. Sidney A Spector12,
  21. James L’Italien12,
  22. Douglas M Sproule12,
  23. Francesco Muntoni11,13
  1. 1Clinic for Special Children, Strasburg, PA, USA
  2. 2Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
  3. 3Department of Neurology, Sydney Children’s Hospital Network, Randwick, NSW, Australia
  4. 4Department of Pediatrics, Children’s Hospital of Eastern Ontario, Ottawa, Canada
  5. 5Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA
  6. 6Department of Neurology, Helen DeVos Children’s Hospital, Grand Rapids, MI, USA
  7. 7Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA
  8. 8Division of Pediatric Neurology, Columbia University Medical Center, New York, NY, USA
  9. 9Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
  10. 10Institute of Medical Genetics, Tokyo Women’s Medical University, Tokyo, Japan
  11. 11The Dubowitz Neuromuscular Centre, University College London, Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, UK
  12. 12AveXis, Inc., Bannockburn, IL, USA
  13. 13National Institute of Health Research, Great Ormond Street Hospital Biomedical Research Centre, London, UK


Background Onasemnogene abeparvovec (AVXS-101) is a gene-replacement therapy that treats the genetic root cause of SMA, biallelic survival motor neuron 1 gene (SMN1) deletion/mutation. In a phase 1 study, AVXS-101 improved survival and motor function of symptomatic SMA type 1 patients. In SPR1NT (NCT03505099), AVXS-101 is being evaluated in presymptomatic newborns with SMA.

Methods SPR1NT is a multicenter, open-label, phase 3 study enrolling ≥27 SMA patients with 2xSMN2 or 3xSMN2. Asymptomatic infants aged ≤6 weeks receive a one-time, intravenous AVXS-101 infusion. Safety and efficacy are assessed through 18 or 24 months for patients with 2x or 3xSMN2, respectively. Primary outcomes are independent sitting ≥30 seconds (2xSMN2) or assisted standing (3xSMN2).

Results As of 8 March 2019, 18 infants aged 8–40 days received AVXS-101 (11 female; 8 with 2xSMN2; 9 with 3xSMN2; 1 with 4xSMN2). Among patients with 2xSMN2, mean CHOP-INTEND at baseline was 44.0 points, which increased by 14.4 points at 3 months (n=7); 6/8 patients scored ≥60 points; 3/8 reached maximum score. 4/8 patients sat unassisted; all ages of sitting milestone achievements were within the WHO range (1st–99th percentile: 3.8–9.2 months).

Conclusions Preliminary data from SPR1NT show rapid motor function improvements in presymptomatic SMA patients.

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