SMA1 is a rapidly progressing and debilitating neurodegenerative disease resulting from bi-allelic survival motor neuron 1 (SMN1) gene deletion/mutation and subsequent motor neuron loss, muscle weakness, respiratory failure, hospitalization, poor quality of life, and early death.

Twelve SMA1 patients (enrolled: December 2014 – December 2015) were treated with a one-time intravenous proposed therapeutic dose of AVXS-101 (CL-101; NCT02122952; cohort 2). Patients were followed for 2 years post-treatment for event-free survival (composite endpoint of time-to-death or permanent ventilation), pulmonary/nutritional interventions, swallow function, hospitalization rates, motor function, CHOP-INTEND, and safety.

All 12 patients survived; none required permanent ventilation. Seven infants did not require noninvasive ventilation 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 (SD=0.41, range=0-4.8) respiratory hospitalizations/year. The mean proportion of time hospitalized was 4.4% (range=0-18.3%); mean unadjusted rate of hospitalization/year was 2.1 (range=0-7.6), with a mean length of stay/hospitalization of 6.7 (range=3-12.1) days. Rapid increases in CHOP-INTEND of 9.8 (SD=3.9) and 15.4 (SD=6.4) points were observed at 1- and 3-months post-treatment, respectively. At long-term follow-up, 11 patients sat unassisted, 4 stood with assistance, and 2 walked independently. Adverse events included elevated serum aminotransferase levels, which were attenuated by prednisolone. 

A single dose of AVXS-101 in CL-101 study resulted in rapid and sustained improvement in CHOP-INTEND scores, leading to dramatic survival and motor function improvements at long-term follow-up (NCT03421977), viewed as a clinical demonstration of continuous SMN expression. The reduced healthcare utilization in treated infants could decrease cost and potentially alleviate patient, caregiver, and societal burden, suggesting an overall improved quality of life.