Long-term safety and efficacy of zilucoplan in patients with generalized myasthenia gravis: interim analysis of the RAISE-XT open-label extension study

Media type: E-Article
Title: Long-term safety and efficacy of zilucoplan in patients with generalized myasthenia gravis: interim analysis of the RAISE-XT open-label extension study
Contributor: Howard, James F.; Bresch, Saskia; Farmakidis, Constantine; Freimer, Miriam; Genge, Angela; Hewamadduma, Channa; Hinton, John; Hussain, Yessar; Juntas-Morales, Raul; Kaminski, Henry J.; Maniaol, Angelina; Mantegazza, Renato; Masuda, Masayuki; Nowak, Richard J.; Sivakumar, Kumaraswamy; Śmiłowski, Marek; Utsugisawa, Kimiaki; Vu, Tuan; Weiss, Michael D.; Zajda, Małgorzata; Bloemers, Jos; Boroojerdi, Babak; Brock, Melissa; de la Borderie, Guillemette; [...]
imprint: SAGE Publications, 2024
Published in: Therapeutic Advances in Neurological Disorders
Language: English
DOI: 10.1177/17562864241243186
ISSN: 1756-2864
Origination:
Footnote:
Description: <jats:sec><jats:title>Background:</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Objectives:</jats:title><jats:p> To evaluate the long-term safety, tolerability, and efficacy of zilucoplan in a mild-to-severe, acetylcholine receptor autoantibody-positive (AChR+) gMG population. </jats:p></jats:sec><jats:sec><jats:title>Design:</jats:title><jats:p> Ongoing, multicenter, phase III open-label extension (OLE) study. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Trial registration:</jats:title><jats:p> ClinicalTrials.gov identifier: NCT04225871 ( https://clinicaltrials.gov/ct2/show/NCT04225871 ) </jats:p></jats:sec>
Access State: Open Access

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