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

Acsadi, Gyula; Crawford, Thomas O.; Mueller-Felber, Wolfgang; Shieh, Perry B.; Richardson, Randal; Natarajan, Niranjana; Castro, Diana; Ramirez-Schrempp, Daniela; Gambino, Giulia; Sun, Peng und Farwell, Wildon (2021): Safety and efficacy of nusinersen in spinal muscular atrophy: The EMBRACE study. In: Muscle & Nerve, Bd. 63, Nr. 5: S. 668-677

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 (similar to 14 months) and subsequently received open-label nusinersen for similar to 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0148-639X
• Sprache: Englisch