Background: NURTURE is an ongoing study (NCT02386553) of intrathecal nusinersen initiated in presymptomatic infants with 2 or 3 SMN2 copies. Enrolled infants were ?6 weeks of age at first dose, clinically presymptomatic, and genetically diagnosed with 5q SMA. The primary endpoint is time to death or respiratory intervention (?6 hours/day continuously for ?7 days or tracheostomy).
Objectives: To present interim results (4.9 years follow up) from the NURTURE study.
Results: NURTURE enrolled 25 infants (2 SMN2 copies, n=15; 3 SMN2 copies, n=10). As of 15 February 2021, the mean time on study was 4.9 years (range: 3.9-5.7). All infants were alive and none required permanent ventilation. Four infants (all with 2 SMN2 copies) required respiratory intervention for ?6 hours/day continuously for ?7 days, with all cases initiated during an acute reversible illness. The median time to death or respiratory intervention could not be estimated because of no or too few events, respectively. All 25 infants achieved the WHO motor milestone of sitting without support, 24/25 (96%) were able to walk with assistance, and 23/25 (92%) were walking alone. Most children achieved these motor milestones (21/25 [84%] sitting without support, 15/25 [60%] walking with assistance, and 16/25 [64%] independent walking) within the 99th percentile age window established by the WHO for healthy children. No motor skills gained were lost during the observation period. Nearly all children (22/25 [88%]) reached the maximum score on the CHOP INTEND scale. Mean (SE) change improvement from baseline (first evaluable assessment after Day 700) in HFMSE scores continued to show improvement over time (16.1 [2.4] at month 36; n=11). No new safety concerns were identified.
Conclusions: These data demonstrate the continued long-term safety and benefit of infants who initiated nusinersen before onset of SMA symptoms, emphasizing the value of newborn screening/early treatment.
Study Support: Biogen