Nusinersen in infants who initiate treatment in a presymptomatic stage of spinal muscular atrophy (SMA): Interim results from the phase 2 nurture study

Abstract

Nusinersen is the first approved treatment for SMA. We present interim results from the ongoing NURTURE study (NCT02386553) examining efficacy/safety of intrathecal nusinersen, initiated prior to symptom onset, in infants with 2 or 3 SMN2 copies. Enrolled infants were age ≤ 6 weeks at first dose, clinically presymptomatic, and genetically diagnosed with SMA. Primary endpoint is time to death or respiratory intervention (≥6 h/day continuously for ≥7 days or tracheostomy). Patient consent/IRB approval were obtained. As of 15 May 2018, 25 infants (2 copies SMN2 [n = 15]; 3 copies [n = 10]) were enrolled. Median age at last visit was 26.0 (range:14.0–34.3) months. All infants were alive and none required permanent ventilation. Median time to death or respiratory intervention could not be estimated because of too few events. Four infants (all 2 SMN2 copies) required respiratory intervention for ≥6 h/day continuously for ≥7 days, with all cases initiated during acute, reversible illness. All infants achieved the WHO motor milestone sitting without support and 22/25 (88%) achieved walking with assistance; 17/22 (77%) were walking alone. Phosphorylated neurofilament heavy chain levels rapidly declined during the nusinersen loading phase and then stabilized. AEs occurred in all infants; 20/25 had mild/moderate AEs; 9 had SAEs. No new safety concerns were identified. Results from a new, Spring 2019 interim analysis, including additional assessments, will be presented. There was continued benefit to infants who initiated nusinersen before symptom onset, emphasizing the value of early treatment and newborn screening. Updated analyses will provide further information. Originally presented at CureSMA 2019.