Neuropediatrics 2017; 48(S 01): S1-S45
DOI: 10.1055/s-0037-1602912
OP – Oral Presentations
Georg Thieme Verlag KG Stuttgart · New York

Interim Efficacy and Safety Results from the Phase 3 ENDEAR Study of Nusinersen in Infants Diagnosed with Spinal Muscular Atrophy (SMA)

R. Finkel1, N. Kuntz2, E. Mercuri3, F. Muntoni4, C. A. Chiriboga5, B. Darras6, H. Topaloglu7, J. Montes5, J. Su8, Z. J. Zhong9, S. Gheuens9, C. F. Bennett8, E. Schneider8, W. Farwell9
  • 1Nemours Children’s Health System, Orlando, Florida, United States
  • 2Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois, United States
  • 3Università Cattolica del Sacro Cuore, Rome, Italy
  • 4University College London, London, United Kingdom
  • 5Columbia University, New York, New York, United States
  • 6Boston Children’s Hospital, Boston, Massachusetts, United States
  • 7Hacettepe University, Ankara, Turkey
  • 8Ionis Pharmaceuticals, Inc., Carlsbad, California, United States
  • 9Biogen, Cambridge, Massachusetts, United States
Further Information

Publication History

Publication Date:
26 April 2017 (online)


Background/Purpose: Nusinersen is an antisense oligonucleotide that modifies SMN2 pre-mRNA splicing. Interim results of the phase 3, randomized, double-blind, sham procedure-controlled ENDEAR study (NCT02193074) evaluating nusinersen in infants with SMA are reported.

Methods: Symptomatic infants diagnosed with SMA (with clinical features consistent with Type 1 SMA) were randomized (2:1) to receive intrathecal nusinersen (12-mg scaled equivalent dose) or sham procedure. Key eligibility criteria included genetic diagnosis of SMA, 2 SMN2 gene copies, and age ≤7 months with no hypoxemia at screening. The interim analysis primary endpoint was the proportion of motor milestone responders using modified section 2 of the Hammersmith Infant Neurological Examination (HINE; defined as more HINE categories improving [≥2-point increase/maximal score in kicking ability, or ≥1-point increase in head control, rolling, sitting, crawling, standing, or walking] than worsening). A predefined interim efficacy analysis was conducted after approximately 80 participants were expected to complete Day 183 visit.

Results: 80 and 41 patients were treated with nusinersen or sham procedure, respectively. Baseline demographics were similar except for age and geographic region. A significantly greater proportion of motor milestone responders was observed in nusinersen-treated versus control patients (p < 0.0001). No adverse events (AEs) were considered related by the investigator; 11% of nusinersen-treated versus 15% of control patients had AEs considered possibly treatment related by the investigator. Additional interim results will be presented.

Conclusion: Nusinersen-treated patients demonstrated a clinically and statistically significantly greater percentage of motor milestone responders versus control, meeting the prespecified interim efficacy analysis primary endpoint. Nusinersen demonstrated a favorable safety profile.