Effect of Zilucoplan on Myasthenia Gravis–Specific Outcome Subdomain Scores in RAISE: A Phase 3 Study
Michael D. Weiss1, Constantine Farmakidis2, Miriam Freimer3, Angela Genge4, Channa Hewamadduma5, Yessar Hussain6, M. Isabel Leite7, Angelina Maniaol8, Kimiaki Utsugisawa9, Tuan Vu10, Babak Boroojerdi11, Fiona Grimson12, Natasa Savic13, James F. Howard Jr.14
1Department of Neurology, University of Washington Medical Center, Seattle, WA, USA, 2Department of Neurology, Neuromuscular Division, University of Kansas Medical Center, Kansas City, KS, USA, 3Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, USA, 4Clinical Research Unit, The Montreal Neurological Institute, Montreal, QC, Canada, 5Academic Neuroscience Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK; Sheffield Institute for Translational Neurosciences (SITraN), University of Sheffield, Sheffield, UK, 6Department of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA, 7Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK, 8Department of Neurology, Oslo University Hospital, Oslo, Norway, 9Department of Neurology, Hanamaki General Hospital, Hanamaki, Japan, 10Department of Neurology, University of South Florida Morsani College of Medicine, Tampa, FL, USA, 11UCB, Monheim, Germany, 12UCB, Slough, UK, 13UCB, Bulle, Switzerland, 14Department of Neurology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Objective:
To evaluate the effect of zilucoplan, a macrocyclic peptide complement component 5 inhibitor, on Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) subdomain scores (ocular, bulbar, respiratory and limb/axial muscle groups) in patients with generalized myasthenia gravis (gMG).
Background:
In RAISE (NCT04115293), zilucoplan demonstrated rapid and clinically meaningful improvements in MG-ADL and QMG total scores vs placebo in adults with acetylcholine receptor autoantibody–positive gMG. Since gMG affects a range of muscle groups, analysis of efficacy within specific muscle groups will enhance understanding of zilucoplan treatment in patients with gMG.
Design/Methods:
Patients in RAISE, a Phase 3, multicenter, double blind, placebo-controlled study, were randomized to self-administer daily subcutaneous injections of zilucoplan 0.3 mg/kg (n=86) or placebo (n=88) for 12
weeks. Primary endpoint: change from baseline (CFB) in MG-ADL total score at Week
12. This exploratory analysis of RAISE data assessed CFB in MG-ADL and QMG subdomain scores for patients with baseline score ≥1 in that subdomain.
Results:
At Week 12, least-squares mean (LSM) (95% CI) CFB in MG-ADL total score was: zilucoplan –4.39 (–5.28, –3.50) and placebo –2.30 (–3.17, –1.43); difference –2.09 [–3.24, –0.95]; p=0.0004. LSM CFB in QMG total score was: zilucoplan –6.19 (–7.29, –5.08) and placebo –3.25 (–4.32, –2.17); difference –2.94 (–4.39, –1.49); p<0.0001. Mean (standard deviation [SD]) CFB in MG-ADL subdomain scores (zilucoplan vs placebo) were: ocular, –1.5 (1.7) vs –0.8 (1.6); bulbar, –1.9 (1.8) vs –1.1 (1.7); respiratory, –0.4 (0.6) vs –0.3 (0.7); limb/axial, −1.2 (1.5) vs –0.8 (1.4), respectively. Mean (SD) CFB in QMG subdomain scores were: ocular, −2.0 (2.1) vs −1.3 (2.2); bulbar, −1.6 (1.4) vs −1.1 (1.5); respiratory, −0.6 (0.7) vs −0.3 (0.8); limb/axial, −2.9 (2.6) vs −1.2 (2.4), respectively.
Conclusions:
Zilucoplan treatment led to improvements relative to placebo across all subdomain scores in MG-ADL and QMG.
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