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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

Title: Long-term safety and efficacy of zilucoplan in patients with generalized myasthenia gravis: interim analysis of the RAISE-XT open-label extension study
Authors: Howard, JF; Bresch, S; Farmakidis, C; Freimer, M; Genge, A; Hewamadduma, C; Hinton, J; Hussain, Y; Juntas-Morales, R; Kaminski, HJ; Maniaol, A; Mantegazza, R; Masuda, M; Nowak, RJ; Sivakumar, K; Śmiłowski, M; Utsugisawa, K; Vu, T; Weiss, MD; Zajda, M; Bloemers, J; Boroojerdi, B; Brock, M; de la Borderie, G; Leite, MI
Publisher Information: SAGE Publications
Publication Year: 2025
Collection: Oxford University Research Archive (ORA)
Description: BackgroundGeneralized 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.ObjectivesTo evaluate the long-term safety, tolerability, and efficacy of zilucoplan in a mild-to-severe, acetylcholine receptor autoantibody-positive (AChR+) gMG population.DesignOngoing, multicenter, phase III open-label extension (OLE) study.MethodsEligible 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.ResultsIn 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.ConclusionZilucoplan 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 ...
Document Type: article in journal/newspaper
Language: English
Relation: https://doi.org/10.1177/17562864241243186
DOI: 10.1177/17562864241243186
Availability: https://doi.org/10.1177/17562864241243186; https://ora.ox.ac.uk/objects/uuid:fd1440dc-ef48-4290-b665-d4ea9b9c4ec6
Rights: info:eu-repo/semantics/openAccess ; CC Attribution-NonCommercial (CC BY-NC)
Accession Number: edsbas.1A48A9F
Database: BASE