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Safety and efficacy of nusinersen in spinal muscular atrophy: The EMBRACE study
Author(s) -
Acsadi Gyula,
Crawford Thomas O.,
MüllerFelber Wolfgang,
Shieh Perry B.,
Richardson Randal,
Natarajan Niranjana,
Castro Diana,
RamirezSchrempp Daniela,
Gambino Giulia,
Sun Peng,
Farwell Wildon
Publication year - 2021
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.27187
Subject(s) - spinal muscular atrophy , sma* , medicine , milestone , adverse effect , population , motor function , randomized controlled trial , surgery , anesthesia , physical medicine and rehabilitation , mathematics , disease , archaeology , environmental health , combinatorics , history
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.