Safety and efficacy of nusinersen in spinal muscular atrophy: The EMBRACE study

Muscle Nerve. 2021 May;63(5):668-677. doi: 10.1002/mus.27187. Epub 2021 Feb 16.


Introduction: The EMBRACE study (Clinical Trials No. NCT02462759) evaluated nusinersen in infants/children with infantile- or later-onset spinal muscular atrophy (SMA) who were ineligible for the ENDEAR and CHERISH studies.

Methods: Participants were randomized to intrathecal nusinersen (12-mg scaled equivalent dose; n = 14) or sham procedure (n = 7) in part 1 (~14 months) and subsequently received open-label nusinersen for ~24 months in part 2 of the study.

Results: Part 1 was stopped early after the demonstration of motor function benefit with nusinersen in ENDEAR. There were no nusinersen-related adverse events (AEs) and no study discontinuations due to nusinersen-related AEs. The most common AEs included pyrexia, cough, pneumonia, and upper respiratory tract infections. Motor milestone responder rates were higher in those receiving nusinersen at last available assessment (93%) than in those receiving sham procedure in part 1 (29%) or transitioned from sham to nusinersen in part 2 (83%). This functional improvement was observed despite the small sample size and shortened part 1 trial duration that undermined the power of the study to demonstrate such treatment effects at a significant level.

Discussion: Nusinersen demonstrated a favorable long-term benefit-risk profile in this broad population of individuals with infantile- or later-onset SMA.

Keywords: clinical tria; nusinersen; safety; spinal muscular atrophy; therapeutic use.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Child, Preschool
  • Double-Blind Method
  • Female
  • Humans
  • Infant
  • Injections, Spinal
  • Male
  • Oligonucleotides / adverse effects
  • Oligonucleotides / therapeutic use*
  • Spinal Muscular Atrophies of Childhood / drug therapy*
  • Treatment Outcome


  • Oligonucleotides
  • nusinersen

Associated data