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014 AVXS-101 gene-replacement therapy (GRT) in presymptomatic spinal muscular atrophy (SMA): study update
  1. Michelle Farrar1,
  2. Kathryn J Swoboda2,
  3. Meredith Schultz3,
  4. Hugh McMillan4,
  5. Julie Parsons5,
  6. Ian E Alexander6,
  7. Elaine Kernbauer3,
  8. Marcia Farrow3,
  9. Francis G Ogrinc3,
  10. Douglas E Feltner3,
  11. Bryan E McGill3,
  12. Sidney A Spector3,
  13. James L’Italien3,
  14. Douglas M Sproule3,
  15. Kevin A Strauss7
  1. 1Department of Neurology, Sydney Children’s Hospital, Randwick, NSW, Australia
  2. 2Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
  3. 3AveXis, Inc., Bannockburn, IL, USA
  4. 4Department of Pediatrics, Canada Children’s Hospital of Eastern Ontario, Ontario, Ottawa, Canada
  5. 5Department of Neurology, Children’s Hospital Colorado, Aurora, CO, USA
  6. 6Gene Therapy Research Unit, Children’s Medical Research Institute and The Children’s Hospital at Westmead, Sydney, NSW, Australia
  7. 7Clinic for Special Children, Strasburg, PA, USA


Introduction SMA is a neurodegenerative disease caused by biallelic deletion/mutation of the survival motor neuron 1 gene (SMN1). Copies of a similar gene (SMN2) modify disease severity. In a phase 1 study, SMN GRT onasemnogene abeparvovec (AVXS-101) improved outcomes of symptomatic SMA patients with two SMN2 copies (2xSMN2) dosed ≤6 months. Because motor neuron loss can be insidious and disease progression is rapid, early intervention is critical. This study evaluates AVXS-101 in presymptomatic SMA newborns.

Methods SPR1NT is a multicenter, open-label, phase 3 study (NCT03505099) enrolling ≥27 SMA patients with 2–3xSMN2. Asymptomatic infants ≤6 weeks receive a one-time intravenous AVXS-101 infusion (1.1×1014 vg/kg). Safety and efficacy are assessed through study end (18 [2xSMN2] or 24 months [3xSMN2]). Primary outcomes: independent sitting for ≥30 seconds (18 months [2xSMN2]) or assisted standing (24 months [3xSMN2]).

Results From April–September 2018, 7 infants received AVXS-101 (4 female; 6 with 2xSMN2) at ages 8–37 days. Mean baseline Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score was 41.7 (n=6), which increased by 6.8, 11.0, 18.0, and 22.5 points at day 14 (n=4), month 1 (n=3), 2 (n=3), and 3 (n=2). As of January 31, 2019, 15 asymptomatic infants have been enrolled in SPR1NT and dosed with AVXS-101. Updated data available at the time of the congress will be presented.

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

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