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


James F. Howard, 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.
Saskia Bresch, Service de Neurologie, Hospital Pasteur, Centre Hospitalier Universitaire de Nice, Nice, France.
Constantine Farmakidis, Neuromuscular Division, Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA.
Miriam Freimer, Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Angela Genge, Clinical Research Unit, Montreal Neurological Institute, Montreal, QC, Canada.
Channa Hewamadduma, Academic Neuroscience Unit, Sheffield Teaching Hospitals Foundation Trust, Sheffield, UK.
John Hinton, Department of Neurology, Frederick P. Whiddon School of Medicine, University of South Alabama, Mobile, AL, USA.
Yessar Hussain, Department of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.
Raul Juntas-Morales, Department of Neurology, Vall d'Hebron University Hospital, Barcelona, Spain.
Henry J. Kaminski, Department of Neurology and Rehabilitation Medicine, George Washington University, Washington, DC, USA.
Angelina Maniaol, Department of Neurology, Oslo University Hospital, Oslo, Norway.
Renato Mantegazza, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale Neurologico Carlo Besta, Milan, Italy.
Masayuki Masuda, Department of Neurology, Tokyo Medical University, Tokyo, Japan.
Richard J. Nowak, Department of Neurology, Yale School of Medicine, New Haven, CT, USA.
Kumaraswamy Sivakumar, Neuromuscular Clinic and Research Center, Phoenix, AZ, USA.
Marek Śmiłowski, Department of Hematology and Bone Marrow Transplantation, Medical University of Silesia, Katowice, Poland.
Kimiaki Utsugisawa, Department of Neurology, Hanamaki General Hospital, Hanamaki, Japan.
Tuan Vu, Department of Neurology, University of South Florida Morsani College of Medicine, Tampa, FL, USA.
Michael D. Weiss, Department of Neurology, University of Washington Medical Center, Seattle, WA, USA.
Małgorzata Zajda, Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland.
Jos Bloemers, UCB Pharma, Brussels, Belgium.
Babak Boroojerdi, UCB Pharma, Monheim am Rhein, Germany.
Melissa Brock, UCB Pharma, Raleigh, NC, USA.
Guillemette de la Borderie, UCB Pharma, Brussels, Belgium.
Petra W. Duda, UCB Pharma, Cambridge, MA, USA.
Mark Vanderkelen, UCB Pharma, Braine-L'Alleud, Belgium.
M Isabel Leite, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.

Document Type

Journal Article

Publication Date



Therapeutic advances in neurological disorders






C5 inhibitor; clinical trial; myasthenia gravis; open-label extension; zilucoplan


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 ( = 52, 26%) and COVID-19 ( = 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).