SMA – THERAPY: P.268 Nusinersen effect in infants who initiate treatment in a presymptomatic stage of SMA: NURTURE results

Abstract

We present interim results from the ongoing NURTURE study (NCT02386553) of intrathecal nusinersen initiated in presymptomatic infants with 2 or 3 SMN2 copies. Enrolled infants were ≤6 weeks at first dose, clinically presymptomatic, and genetically diagnosed with SMA. Primary endpoint is time to death or respiratory intervention (≥ 6 hours/day continuously for ≥ 7 days or tracheostomy). NURTURE has enrolled 25 infants (2 copies SMN2, n = 15; 3 copies, n = 10). As of 29 March 2019, median age at last visit was 34.8 (range 25.7–45.4) months. All infants were alive and none required permanent ventilation. Four infants (all with 2 SMN2 copies) required respiratory intervention over the course of the study, with all cases initiated during an acute reversible illness. Median time to death or respiratory intervention could not be estimated because of too few events. All 25 infants achieved the World Health Organization (WHO) motor milestone of sitting without support, 23/25 (92%) achieved walking with assistance, and 22/25 (88%) were walking alone. Most children achieved these motor milestones (21/25 [84%] sitting without support, 15/23 [65%] walking with assistance, and 16/22 [73%] independent walking) within the 99th percentile age window established by the WHO for healthy children. Nearly all children reached the maximum score on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) scale. Phosphorylated neurofilament heavy chain (pNF-H) levels rapidly declined during the loading phase of nusinersen and then stabilized. Plasma pNF-H levels at Day 64 were significantly correlated with the WHO motor milestone walking alone age (Spearman's r = 0.64; p = 0.0025; n = 20). No new safety concerns were identified. Results from a new Spring 2020 interim analysis will be presented. These data demonstrate the continued benefit to infants who initiated nusinersen before symptom onset, emphasizing the value of newborn screening/early treatment.