학술논문
Long-term safety and efficacy of zilucoplan in patients with generalized myasthenia gravis: interim analysis of the RAISE-XT open-label extension study.
Document Type
Academic Journal
Author
Howard JF Jr; Department of Neurology, UNC School of Medicine, The University College of North Carolina at Chapel Hill, 2200 Houpt Building, CB#7025, 170 Manning Drive, Chapel Hill, NC 27599-7025, 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.; Hinton J; Department of Neurology, Frederick P. Whiddon School of Medicine, University of South Alabama, Mobile, AL, USA.; Hussain Y; Department of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.; Juntas-Morales R; Department of Neurology, Vall d'Hebron University Hospital, Barcelona, Spain.; Kaminski HJ; Department of Neurology and Rehabilitation Medicine, George Washington University, Washington, DC, USA.; Maniaol A; Department of Neurology, Oslo University Hospital, Oslo, Norway.; Mantegazza R; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale Neurologico Carlo Besta, Milan, Italy.; Masuda M; Department of Neurology, Tokyo Medical University, Tokyo, Japan.; Nowak RJ; Department of Neurology, Yale School of Medicine, New Haven, CT, USA.; Sivakumar K; Neuromuscular Clinic and Research Center, Phoenix, AZ, USA.; Śmiłowski M; Department of Hematology and Bone Marrow Transplantation, Medical University of Silesia, Katowice, Poland.; Utsugisawa K; Department of Neurology, Hanamaki General Hospital, Hanamaki, Japan.; Vu T; Department of Neurology, University of South Florida Morsani College of Medicine, Tampa, FL, USA.; Weiss MD; Department of Neurology, University of Washington Medical Center, Seattle, WA, USA.; Zajda M; Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland.; Bloemers J; UCB Pharma, Brussels, Belgium.; Boroojerdi B; UCB Pharma, Monheim am Rhein, Germany.; Brock M; UCB Pharma, Raleigh, NC, USA.; de la Borderie G; UCB Pharma, Brussels, Belgium.; Duda PW; UCB Pharma, Cambridge, MA, USA.; Vanderkelen M; UCB Pharma, Braine-L'Alleud, Belgium.; Leite MI; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Source
Publisher: SAGE Country of Publication: England NLM ID: 101480242 Publication Model: eCollection Cited Medium: Print ISSN: 1756-2856 (Print) Linking ISSN: 17562856 NLM ISO Abbreviation: Ther Adv Neurol Disord Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
1756-2856
Abstract
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 Author(s), 2024.)
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 Author(s), 2024.)