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

Gyula Acsadi, Thomas O. Crawford, Wolfgang Müller-Felber, Perry B. Shieh, Randal Richardson, Niranjana Natarajan, Diana Castro, Daniela Ramirez-Schrempp, Giulia Gambino, Peng Sun, Wildon Farwell

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)668-677
Number of pages10
JournalMuscle and Nerve
Volume63
Issue number5
DOIs
StatePublished - May 2021

Keywords

  • clinical tria
  • nusinersen
  • safety
  • spinal muscular atrophy
  • therapeutic use

ASJC Scopus subject areas

  • Physiology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Physiology (medical)

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