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-se...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2024-04-01
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| Series: | Therapeutic Advances in Neurological Disorders |
| Online Access: | https://doi.org/10.1177/17562864241243186 |
| _version_ | 1797202173255221248 |
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| author | 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 |
| author_facet | 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 |
| author_sort | James F. Howard |
| collection | DOAJ |
| description | 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 ) |
| first_indexed | 2024-04-24T07:59:14Z |
| format | Article |
| id | doaj.art-5317ded6473646318a630c95493a4cc4 |
| institution | Directory Open Access Journal |
| issn | 1756-2864 |
| language | English |
| last_indexed | 2024-04-24T07:59:14Z |
| publishDate | 2024-04-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Therapeutic Advances in Neurological Disorders |
| spelling | doaj.art-5317ded6473646318a630c95493a4cc42024-04-18T01:03:21ZengSAGE PublishingTherapeutic Advances in Neurological Disorders1756-28642024-04-011710.1177/17562864241243186Long-term safety and efficacy of zilucoplan in patients with generalized myasthenia gravis: interim analysis of the RAISE-XT open-label extension studyJames F. HowardSaskia BreschConstantine FarmakidisMiriam FreimerAngela GengeChanna HewamaddumaJohn HintonYessar HussainRaul Juntas-MoralesHenry J. KaminskiAngelina ManiaolRenato MantegazzaMasayuki MasudaRichard J. NowakKumaraswamy SivakumarMarek ŚmiłowskiKimiaki UtsugisawaTuan VuMichael D. WeissMałgorzata ZajdaJos BloemersBabak BoroojerdiMelissa BrockGuillemette de la BorderiePetra W. DudaMark VanderkelenM. Isabel Leite 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 )https://doi.org/10.1177/17562864241243186 |
| spellingShingle | 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 Long-term safety and efficacy of zilucoplan in patients with generalized myasthenia gravis: interim analysis of the RAISE-XT open-label extension study Therapeutic Advances in Neurological Disorders |
| title | Long-term safety and efficacy of zilucoplan in patients with generalized myasthenia gravis: interim analysis of the RAISE-XT open-label extension study |
| title_full | Long-term safety and efficacy of zilucoplan in patients with generalized myasthenia gravis: interim analysis of the RAISE-XT open-label extension study |
| title_fullStr | Long-term safety and efficacy of zilucoplan in patients with generalized myasthenia gravis: interim analysis of the RAISE-XT open-label extension study |
| title_full_unstemmed | Long-term safety and efficacy of zilucoplan in patients with generalized myasthenia gravis: interim analysis of the RAISE-XT open-label extension study |
| title_short | Long-term safety and efficacy of zilucoplan in patients with generalized myasthenia gravis: interim analysis of the RAISE-XT open-label extension study |
| title_sort | long term safety and efficacy of zilucoplan in patients with generalized myasthenia gravis interim analysis of the raise xt open label extension study |
| url | https://doi.org/10.1177/17562864241243186 |
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