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. Finkel
1  Nemours Children’s Health System, Orlando, Florida, United States
,
N. Kuntz
2  Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois, United States
,
E. Mercuri
3  Università Cattolica del Sacro Cuore, Rome, Italy
,
F. Muntoni
4  University College London, London, United Kingdom
,
C. A. Chiriboga
5  Columbia University, New York, New York, United States
,
B. Darras
6  Boston Children’s Hospital, Boston, Massachusetts, United States
,
H. Topaloglu
7  Hacettepe University, Ankara, Turkey
,
J. Montes
5  Columbia University, New York, New York, United States
,
J. Su
8  Ionis Pharmaceuticals, Inc., Carlsbad, California, United States
,
Z. J. Zhong
9  Biogen, Cambridge, Massachusetts, United States
,
S. Gheuens
9  Biogen, Cambridge, Massachusetts, United States
,
C. F. Bennett
8  Ionis Pharmaceuticals, Inc., Carlsbad, California, United States
,
E. Schneider
8  Ionis Pharmaceuticals, Inc., Carlsbad, California, United States
,
W. Farwell
9  Biogen, Cambridge, Massachusetts, United States
› Author Affiliations
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.