Abstract Details

Fourteen presymptomatic patients (biallelic SMN1 deletions, two SMN2 copies) were enrolled. Primary endpoint was independent sitting for ≥30 seconds (Bayley-III #26) by 18 months. Secondary endpoints were survival (no death/permanent ventilation) at 14 months and maintaining body weight (≥3rd WHO percentile) without feeding support at any visit. Exploratory endpoints included CHOP INTEND and Bayley-III motor scale assessments. Safety evaluations included adverse events (AEs), concomitant medications, physical examinations, vital signs, cardiac indices, and laboratory data. Primary and secondary outcomes were compared with a cohort from the Pediatric Neuromuscular Clinical Research (PNCR) natural history data set.

All primary and secondary endpoints were statistically significant compared with the PNCR cohort (p<0.001). All 14 patients sat independently (11/14 within WHO-MGRS developmental window), all survived without permanent ventilation, and 13 (93%) maintained body weight without feeding support. No patient used nutritional/respiratory support (including cough assist). Eleven patients stood (Bayley-III #40) and nine walked (Bayley-III #43) (7/11 and 5/9 within WHO-MGRS developmental windows, respectively). All patients achieved CHOP INTEND score of ≥58 (maximum score=64) during at least one follow-up visit. All 14 demonstrated ≥15-point improvement in Bayley-III motor scale scores. All patients had AEs. Pyrexia, upper respiratory tract infection, and constipation were most common. Ten patients (71%) had at least one treatment-related AE. No serious AEs were considered treatment-related by investigator.