Subgroup outcomes from RAISE: A randomized, Phase 3 trial of zilucoplan in generalized myasthenia gravis
Michael D. Weiss1, Saskia Bresch2, Miriam Freimer3, Channa Hewamadduma4, Raul Juntas-Morales5, M. Isabel Leite6, Angelina Maniaol7, Masayuki Masuda8, Kumaraswamy Sivakumar9, Malgorzata Zajda10, Babak Boroojerdi11, Petra W. Duda12, Guillemette De La Borderie13, James F. Howard Jr.14
1University of Washington Medical Center, Department of Neurology, 2Centre Hospitalier Universitaire de Nice, 3The Ohio State University, 4Department of Neuroscience, University of Sheffield, 5Vall d’Hebron University Hospital, 6Nuffield Department of Clinical Neurosciences - University of Oxford, 7Department of Neurology, Oslo University Hospital, 8Department of Neurology, Tokyo Medical University, 9University of Arizona, School of Medicine, Neuromuscular Clinic and Research Center, 10Medical University of Warsaw, 11UCB Pharma, Monheim, Germany, 12UCB Pharma, Cambridge, MA, USA, 13UCB Pharma, Brussels, Belgium, 14Department of Neurology, The University of North Carolina
Objective:
To evaluate the efficacy of zilucoplan in patients with acetylcholine receptor autoantibody positive (AChR Ab+) generalized myasthenia gravis (gMG), stratified to specific disease characteristics.
Background:
RAISE (NCT04115293) was a Phase 3, multicenter, double-blind, placebo-controlled study of zilucoplan, a macrocyclic peptide inhibitor of complement C5, that resulted in statistically significant and clinically meaningful improvement in MG-related efficacy endpoints (primary endpoint: MG-ADL score; LS mean change from baseline [CFB] in zilucoplan: −4.39 vs placebo −2.30, difference −2.09, p<0.001), in patients with AChR Ab+ gMG.
Design/Methods:
Adult participants (MGFA Disease Class II–IV gMG, AChR Ab+, MG-ADL score ≥6, QMG score ≥12) were randomized 1:1 to daily subcutaneous doses of zilucoplan 0.3 mg/kg or matched placebo for 12 weeks. The primary efficacy endpoint was CFB at Week 12 in MG-ADL score. Subgroups were pre-specified according to the following baseline disease characteristics: MG-ADL ≤9 or ≥10, QMG ≤17 or ≥18, and disease duration <5 or ≥5 years.
Results:
Overall, 174 participants were randomized to zilucoplan (n=86) or placebo (n=88). At Week 12, the mean CFB in MG-ADL for zilucoplan vs placebo was consistently improved in each subgroup: baseline MG-ADL: ≤9: −3.88 vs −2.48 and ≥10: −5.24 vs −3.06; baseline QMG: ≤17: −4.19 vs −2.81 and ≥18: −5.11 vs −2.88; and duration of disease: <5 years: −3.92 vs −3.04 and ≥5 years: −5.38 vs −2.62. Mean CFB at Week 12 for QMG and MGC were also consistently improved with zilucoplan vs placebo, across all subgroups. Zilucoplan showed a favorable safety profile and was well-tolerated.
Conclusions:
Daily subcutaneous zilucoplan demonstrated consistent improvements in MG-specific efficacy outcomes irrespective of disease severity or duration. Funding: UCB Pharma.