PMID- 33501671 OWN - NLM STAT- MEDLINE DCOM- 20210610 LR - 20210703 IS - 1097-4598 (Electronic) IS - 0148-639X (Print) IS - 0148-639X (Linking) VI - 63 IP - 5 DP - 2021 May TI - Safety and efficacy of nusinersen in spinal muscular atrophy: The EMBRACE study. PG - 668-677 LID - 10.1002/mus.27187 [doi] AB - 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. CI - (c) 2021 The Authors. Muscle & Nerve published by Wiley Periodicals LLC. FAU - Acsadi, Gyula AU - Acsadi G AD - Division of Pediatric Neurology, Connecticut Children's Medical Center, University of Connecticut School of Medicine, Farmington, Connecticut, USA. FAU - Crawford, Thomas O AU - Crawford TO AUID- ORCID: 0000-0003-0916-2797 AD - Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. FAU - Muller-Felber, Wolfgang AU - Muller-Felber W AD - Department of Neuropediatrics, Developmental Neurology and Social Pediatrics, LMU Campus Innenstadt, University of Munich, Munich, Germany. FAU - Shieh, Perry B AU - Shieh PB AUID- ORCID: 0000-0001-7145-7663 AD - Department of Neurology, UCLA Clinical and Translational Research Center, Los Angeles, California, USA. FAU - Richardson, Randal AU - Richardson R AD - Pediatric Neurology, Gillette Children's Specialty Healthcare, St Paul, Minnesota, USA. FAU - Natarajan, Niranjana AU - Natarajan N AD - Department of Neurology, Seattle Children's Research Institute, Seattle, Washington, USA. FAU - Castro, Diana AU - Castro D AD - Department of Pediatrics, Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, Texas, USA. FAU - Ramirez-Schrempp, Daniela AU - Ramirez-Schrempp D AD - Biogen, Cambridge, Massachusetts, USA. FAU - Gambino, Giulia AU - Gambino G AD - Biogen, Maidenhead, UK. FAU - Sun, Peng AU - Sun P AD - Biogen, Cambridge, Massachusetts, USA. FAU - Farwell, Wildon AU - Farwell W AD - Biogen, Cambridge, Massachusetts, USA. LA - eng SI - ClinicalTrials.gov/NCT02462759 PT - Journal Article PT - Randomized Controlled Trial DEP - 20210216 PL - United States TA - Muscle Nerve JT - Muscle & nerve JID - 7803146 RN - 0 (Oligonucleotides) RN - 5Z9SP3X666 (nusinersen) SB - IM MH - Child, Preschool MH - Double-Blind Method MH - Female MH - Humans MH - Infant MH - Injections, Spinal MH - Male MH - Oligonucleotides/adverse effects/*therapeutic use MH - Spinal Muscular Atrophies of Childhood/*drug therapy MH - Treatment Outcome PMC - PMC8248061 OTO - NOTNLM OT - clinical tria OT - nusinersen OT - safety OT - spinal muscular atrophy OT - therapeutic use COIS- G.A. has participated in advisory boards for AveXis/Novartis, Biogen, Genentech, and Sarepta; and has participated in consultation and speaker engagements for Biogen. T.O.C. has been an advisor/consultant for AveXis/Novartis, Biogen, Catalyst, Cure SMA, Cytokinetics, Marathon, Novartis, Roche, Sarepta, and the SMA Foundation. W.M.-F. has participated in advisory boards for AveXis/Novartis, Biogen, PTC, Roche, and Sarepta; has received honoraria from AveXis/Novartis, Biogen, and PTC; has received research funding from BMBF; and has clinical trial research contracts with Biogen, Santhera, and Sarepta. P.B.S. has participated in advisory boards for Biogen and, outside of the submitted work, has participated in advisory boards for AveXis/Novartis, PTC, and Sarepta. R.R. has participated in advisory boards for AveXis/Novartis and Biogen, and has clinical trial research contracts with Biogen. N.N. has received research funding from Biogen for execution of clinical trial projects and National Institutes of Health funding for site principal investigator work on the HEAL-EEG study. D.C. has participated in advisory board for AveXis/Novartis, Biogen, PTC, and Sarepta; has received research funding from AveXis/Novartis, Biogen, FibroGen, PTC, ReveraGen, and Sarepta; and has participated in medical advisory boards for GBS-CIDP Foundation, Myasthenia Gravis Foundation, and the Cure SMA Care Center Network. D.R.-S., G.G., P.S., and W.F. are employees of and hold stock/stock options in Biogen. EDAT- 2021/01/28 06:00 MHDA- 2021/06/11 06:00 PMCR- 2021/07/01 CRDT- 2021/01/27 05:56 PHST- 2021/01/19 00:00 [revised] PHST- 2020/08/28 00:00 [received] PHST- 2021/01/24 00:00 [accepted] PHST- 2021/01/28 06:00 [pubmed] PHST- 2021/06/11 06:00 [medline] PHST- 2021/01/27 05:56 [entrez] PHST- 2021/07/01 00:00 [pmc-release] AID - MUS27187 [pii] AID - 10.1002/mus.27187 [doi] PST - ppublish SO - Muscle Nerve. 2021 May;63(5):668-677. doi: 10.1002/mus.27187. Epub 2021 Feb 16.