Background: Nusinersen is the first approved treatment for spinal muscular atrophy (SMA).
Objectives: Report 2019 interim results from the ongoing NURTURE study (NCT02386553).
Approach: Enrolled infants were ≤6 wks at first dose, clinically presymptomatic, and genetically diagnosed with SMA. Primary endpoint is time to death or respiratory intervention (≥6 hrs/d continuously for ≥7 d or tracheostomy).
Results: 25 infants (2 copies SMN2, n=15; 3 copies, n=10) were enrolled. As of 29 March 2019, the median (range) age at last visit was 34.8 (25.7–45.4) mo. All infants were alive; none required permanent ventilation. Median time to death or respiratory intervention could not be estimated because of too few events. 4 infants (all 2 SMN2 copies) required respiratory intervention for ≥6 hrs/d continuously for ≥7 d, with all cases initiated during acute, reversible illness. All 25 infants achieved WHO motor milestone sitting without support, 23/25 (92%) walking with assistance, and 22/25 (88%) walking alone. Among these, 84% (21/25) achieved sitting without support, 65% (15/23) walking with assistance, and 73% (16/22) independent walking within the WHO 99th percentile age window. Nearly all reached the CHOP INTEND maximum score. Phosphorylated neurofilament heavy chain (pNF-H) levels rapidly declined during the loading phase of nusinersen and then stabilized. Among characteristics analyzed, baseline plasma pNF-H level was the strongest predictor of age of achievement of WHO motor milestone walking alone (Spearman's r=0.55;p=0.0147;n=19). Plasma pNF-H levels at Day 64 were significantly correlated with the age walking alone was achieved (Spearman's r=0.64;p=0.0025;n=20) with lower pNF-H levels corresponding to earlier achievement. No new safety concerns were identified.
Conclusions: Findings show continued benefit in infants who initiated nusinersen before symptom onset, emphasizing the value of newborn screening and early treatment.
Study Support: Biogen; encore submission; previously presented