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Long-term safety and efficacy of zilucoplan in patients with generalized myasthenia gravis: interim analysis of the RAISE-XT open-label extension study Howard, James Bresch, Saskia Farmakidis, Constantine freimer, miriam genge, angela Hewamadduma, Channa Juntas Morales, Raúl Institut Català de la Salut [Howard JF Jr] Department of Neurology, UNC School of Medicine, The University College of North Carolina at Chapel Hill, Chapel Hill, NC, USA. [Bresch S] Service de Neurologie, Hospital Pasteur, Centre Hospitalier Universitaire de Nice, Nice, France. [Farmakidis C] Neuromuscular Division, Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA. [Freimer M] Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, USA. [Genge A] Clinical Research Unit, Montreal Neurological Institute, Montreal, QC, Canada. [Hewamadduma C] Academic Neuroscience Unit, Sheffield Teaching Hospitals Foundation Trust, Sheffield, UK. Sheffield Institute for Translational Neurosciences (SITRAN), University of Sheffield, Sheffield, UK. [Juntas-Morales R] Servei de Neurologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain Vall d'Hebron Barcelona Hospital Campus Avaluació de resultats (Assistència sanitària) Miastènia greu pseudoparalítica - Tractament Malalties neuromusculars - Tractament Complement (Immunologia) Medicaments immunosupressors - Tractament ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome DISEASES::Nervous System Diseases::Autoimmune Diseases of the Nervous System::Myasthenia Gravis Other subheadings::Other subheadings::Other subheadings::/drug therapy CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Immunologic Factors::Immunosuppressive Agents::Complement Inactivating Agents TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento ENFERMEDADES::enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::miastenia gravis Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::efectos fisiológicos de los fármacos::factores inmunitarios::inmunosupresores::inactivadores del complemento C5 inhibitor; Myasthenia gravis; Zilucoplan Inhibidor de C5; Miastenia gravis; Zilucoplan Inhibidor de C5; Miastènia gravis; Zilucoplan Background: Generalized myasthenia gravis (gMG) is a chronic, unpredictable disease associated with high treatment and disease burdens, with a need for more effective and well-tolerated treatments. Objectives: To evaluate the long-term safety, tolerability, and efficacy of zilucoplan in a mild-to-severe, acetylcholine receptor autoantibody-positive (AChR+) gMG population. Design: Ongoing, multicenter, phase III open-label extension (OLE) study. Methods: Eligible patients had completed a qualifying randomized, placebo-controlled phase II or phase III zilucoplan study and received daily, self-administered subcutaneous 0.3 mg/kg zilucoplan. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs). Secondary efficacy endpoints included change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) score. Results: In total, 200 patients enrolled. At the cut-off date (8 September 2022), median (range) exposure to zilucoplan in RAISE-XT was 1.2 (0.11–4.45) years. Mean age at OLE baseline was 53.3 years. A total of 188 (94%) patients experienced a TEAE, with the most common being MG worsening (n = 52, 26%) and COVID-19 (n = 49, 25%). In patients who received zilucoplan 0.3 mg/kg in the parent study, further improvements in MG-ADL score continued through to Week 24 (least squares mean change [95% confidence interval] from double-blind baseline −6.06 [−7.09, −5.03]) and were sustained through to Week 60 (−6.04 [−7.21, −4.87]). In patients who switched from placebo in the parent study, rapid improvements in MG-ADL score were observed at the first week after switching to zilucoplan; further improvements were observed at Week 24, 12 weeks after switching (−6.46 [−8.19, −4.72]), and were sustained through to Week 60 (−6.51 [−8.37, −4.65]). Consistent results were observed in other efficacy endpoints. Conclusion: Zilucoplan demonstrated a favorable long-term safety profile, good tolerability, and sustained efficacy through to Week 60 with consistent benefits in a broad AChR+ gMG population. Additional long-term data will be available in future analyses. Trial registration: ClinicalTrials.gov identifier: NCT04225871 (https://clinicaltrials.gov/ct2/show/NCT04225871) The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was funded by UCB Pharma. The funding source contributed to the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication. 2024-04-24T11:05:23Z 2024-04-24T11:05:23Z 2024-04-17 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion James F. Howard J, Bresch S, Farmakidis C, Freimer M, Genge A, Hewamadduma C, et al. Long-term safety and efficacy of zilucoplan in patients with generalized myasthenia gravis: interim analysis of the RAISE-XT open-label extension study. Ther Adv Neurol Disord. 2024 Apr 17;17:1–16. 1756-2856 https://hdl.handle.net/11351/11367 10.1177/17562864241243186 38638673 http://hdl.handle.net/11351/11367 eng Therapeutic Advances in Neurological Disorders;17 https://doi.org/10.1177/17562864241243186 Attribution-NonCommercial 4.0 International http://creativecommons.org/licenses/by-nc/4.0/ info:eu-repo/semantics/openAccess application/pdf SAGE Publications Scientia