Long-term Safety and Efficacy of Zilucoplan in Myasthenia Gravis: Additional Interim Analyses of RAISE-XT
James F. Howard1, Miriam Freimer2, Angela Genge3, Channa Hewamadduma4, Yessar Hussain5, Angelina Maniaol6, Renato Mantegazza7, Marek Smilowski8, Kimiaki Utsugisawa9, Tuan Vu10, Michael Weiss11, Petra Duda12, Babak Boroojerdi13, Mark Vanderkelen14, Guillemette De La Borderie15, M. Isabel Leite16
1Department of Neurology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 2Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, USA, 3Clinical Research Unit, The Montreal Neurological Institute, Montreal, QC, Canada, 4Academic Neuroscience Unit, Sheffield Teaching Hospitals Foundation Trust, Sheffield, UK; Sheffield Institute for Translational Neurosciences (SITRAN), University of Sheffield, Sheffield, UK, 5Department of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA, 6Department of Neurology, Oslo University Hospital, Oslo, Norway, 7Department of Neuroimmunology and Neuromuscular Diseases, Fondazione IRCCS, Istituto Nazionale Neurologico Carlo Besta, Milan, Italy, 8Medical University of Silesia, Katowice, Poland, 9Department of Neurology, Hanamaki General Hospital, Hanamaki, Japan, 10Department of Neurology, University of South Florida Morsani College of Medicine, Tampa, FL, USA, 11Department of Neurology, University of Washington Medical Center, Seattle, WA, USA, 12UCB Pharma, Cambridge, MA, USA, 13UCB Pharma, Monheim, Germany, 14UCB Pharma, Braine-l’Alleud, Belgium, 15UCB Pharma, Brussels, Belgium, 16Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
Objective:
To evaluate the long-term safety and efficacy of zilucoplan, a macrocyclic peptide complement component 5 inhibitor, up to 96 weeks in patients with acetylcholine receptor autoantibody-positive (AChR Ab+) generalized myasthenia gravis (gMG) in an interim analysis of RAISE-XT (NCT04225871).
Background:
We previously reported zilucoplan sustained efficacy for up to 60 weeks of treatment, with a favorable safety profile in a broad population of adult patients with AChR Ab+ gMG. RAISE-XT is ongoing and further long-term data will enhance our understanding of the safety and efficacy of zilucoplan in adults with gMG.
Design/Methods:
RAISE-XT, a Phase 3, multicenter, open-label extension study, included patients with gMG who participated in randomized, double-blind, Phase 2 (NCT03315130) and Phase 3 (NCT04115293) zilucoplan studies. All patients self-administered daily subcutaneous injections of zilucoplan 0.3 mg/kg. The primary outcome was incidence of treatment-emergent adverse events (TEAEs). Key secondary outcomes included Myasthenia Gravis Activities of Daily Living (MG-ADL) score.
Results:
In total, 200 patients enrolled in RAISE-XT. At data cut-off (May 11, 2023), median (range) exposure to zilucoplan was 1.8 (0.11–5.1) years. TEAEs occurred in 191 (95.5%) patients and 71 (35.5%) experienced a serious TEAE. The most common TEAEs were COVID-19, occurring in 64 (32.0%) patients, and MG worsening, occurring in 58 (29.0%) patients. At Week 96 of zilucoplan treatment, patients achieved a mean (standard error [SE]) change in MG-ADL score from double-blind study baseline of –6.33 (0.49). For patients who switched from placebo to zilucoplan at the end of the double-blind studies, mean (SE) reduction from baseline in MG-ADL score was –7.83 (0.60).
Conclusions:
In this interim analysis of RAISE-XT, zilucoplan demonstrated a favorable long-term safety profile. Efficacy was sustained through to Week 96 in patients who had previously received zilucoplan and was demonstrated in those who switched from placebo.