James F Howard, Saskia Bresch, Constantine Farmakidis, Miriam Freimer, Angela Genge, Channa Hewamadduma, John Hinton, Yessar Hussain, Raul Juntas-Morales, Henry J Kaminski, Angelina Maniaol, Renato Mantegazza, Masayuki Masuda, Richard J Nowak, Kumaraswamy Sivakumar, Marek Śmiłowski, Kimiaki Utsugisawa, Tuan Vu, Michael D Weiss, Małgorzata Zajda, Jos Bloemers, Babak Boroojerdi, Melissa Brock, Guillemette de la Borderie, Petra W Duda, Mark Vanderkelen, M Isabel Leite
{"title":"齐鲁霉素对全身性肌无力患者的长期安全性和疗效：RAISE-XT 开放标签扩展研究的中期分析。","authors":"James F Howard, Saskia Bresch, Constantine Farmakidis, Miriam Freimer, Angela Genge, Channa Hewamadduma, John Hinton, Yessar Hussain, Raul Juntas-Morales, Henry J Kaminski, Angelina Maniaol, Renato Mantegazza, Masayuki Masuda, Richard J Nowak, Kumaraswamy Sivakumar, Marek Śmiłowski, Kimiaki Utsugisawa, Tuan Vu, Michael D Weiss, Małgorzata Zajda, Jos Bloemers, Babak Boroojerdi, Melissa Brock, Guillemette de la Borderie, Petra W Duda, Mark Vanderkelen, M Isabel Leite","doi":"10.1177/17562864241243186","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>To evaluate the long-term safety, tolerability, and efficacy of zilucoplan in a mild-to-severe, acetylcholine receptor autoantibody-positive (AChR+) gMG population.</p><p><strong>Design: </strong>Ongoing, multicenter, phase III open-label extension (OLE) study.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 (<i>n</i> = 52, 26%) and COVID-19 (<i>n</i> = 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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT04225871 (https://clinicaltrials.gov/ct2/show/NCT04225871).</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241243186"},"PeriodicalIF":4.7000,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11025429/pdf/","citationCount":"0","resultStr":"{\"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\":\"James F Howard, Saskia Bresch, Constantine Farmakidis, Miriam Freimer, Angela Genge, Channa Hewamadduma, John Hinton, Yessar Hussain, Raul Juntas-Morales, Henry J Kaminski, Angelina Maniaol, Renato Mantegazza, Masayuki Masuda, Richard J Nowak, Kumaraswamy Sivakumar, Marek Śmiłowski, Kimiaki Utsugisawa, Tuan Vu, Michael D Weiss, Małgorzata Zajda, Jos Bloemers, Babak Boroojerdi, Melissa Brock, Guillemette de la Borderie, Petra W Duda, Mark Vanderkelen, M Isabel Leite\",\"doi\":\"10.1177/17562864241243186\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>To evaluate the long-term safety, tolerability, and efficacy of zilucoplan in a mild-to-severe, acetylcholine receptor autoantibody-positive (AChR+) gMG population.</p><p><strong>Design: </strong>Ongoing, multicenter, phase III open-label extension (OLE) study.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 (<i>n</i> = 52, 26%) and COVID-19 (<i>n</i> = 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]). 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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.
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.
期刊介绍：
Therapeutic Advances in Neurological Disorders is a peer-reviewed, open access journal delivering the highest quality articles, reviews, and scholarly comment on pioneering efforts and innovative studies across all areas of neurology. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in neurology, providing a forum in print and online for publishing the highest quality articles in this area.
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