PSY16 - HEALTH OUTCOME IMPROVEMENTS IN SPINAL MUSCULAR ATROPHY TYPE 1 PATIENTS WITH AVXS-101 GENE REPLACEMENT THERAPY

Spinal Muscular Atrophy type 1 (SMA1) is a rare genetic and life-threatening neuromuscular disease where afflicted children never sit unassisted. A natural history study reported that 75% of SMA1 patients die/require permanent-ventilation by 13.6 months. This study assessed the health outcomes of SMA1 infants treated with AVXS-101 gene replacement therapy. A cohort of 12 genetically confirmed SMA1 infants with homozygous deletions of the SMN1 gene and two SMN2 gene copies received a one-time intravenous proposed therapeutic dose of AVXS-101 gene replacement therapy in an open label study conducted between May 2014 and December 2017. Patients were followed for 2-years post-treatment for outcomes including (1) pulmonary interventions, (2) nutritional interventions, (3) swallow function, (4) hospitalization rates, and (5) motor function. All 12 patients completed the study. Seven infants did not require noninvasive ventilation (NIV) by study completion. Eleven patients had stable or improved swallowing function, demonstrated by the ability to feed orally, with 6 exclusively fed by mouth. Eleven patients were able to speak. Participants experienced on average 1.4 respiratory hospitalizations per year (SD=0.41, range 0-4.8). The mean proportion of time hospitalized was 4.4% (range=0,18.3%); the mean unadjusted annualized rate of hospitalization was 2.1 (range=0,7.6), with a mean length of stay per hospitalization of 6.7 (range=3,12.1) days. For motor abilities, 11 patients achieved full head control and sitting unassisted and two patients were walking independently. AVXS-101 treatment in SMA1 was associated with reduced pulmonary and nutritional support requirements, improved motor function, and decreased hospitalization rate over the follow-up period. This dramatically contrasts with the natural history of progressive respiratory failure and reduced survival. The reduced healthcare utilization could potentially decrease costs, alleviate patient and caregiver burden, and enable improved functional independence, suggesting an overall improved quality of life for both patients and caregivers following gene replacement therapy.