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 language | English (US) |
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Pages (from-to) | 668-677 |
Number of pages | 10 |
Journal | Muscle and Nerve |
Volume | 63 |
Issue number | 5 |
DOIs | |
State | Published - 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)