Response rates with zilucoplan in generalized myasthenia gravis: 120-week interim analysis of RAISE-XT

Topic:

Clinical Trials

Poster Number: P358

Author(s):

James Howard, MD, Department of Neurology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, Miriam Freimer, MD, Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, USA, Angela Genge, MD, Clinical Research Unit, The Montreal Neurological Institute, Montreal, QC, Canada, Channa Hewamadduma, MBS, FRCP (Neuro), FRCPE, PhD, Academic Neuroscience Unit, Sheffield Teaching Hospitals NHS FT, and SITraN, Univ. of Sheffield, UK, Angelina Maniaol, PhD, Department of Neurology, Oslo University Hospital, Oslo, Norway, Renato Mantegazza, MD, Emeritus & Past Dir., Neuroimmunol. & Neuromusc. Dis., Fondazione IRCCS Carlo Besta, Milan, Italy, Kimiaki Utsugisawa, MD, PhD, Hanamaki General Hospital, Tuan Vu, MD, Department of Neurology, University of South Florida, Tampa, FL, USA, Michael Weiss, MD, Department of Neurology, University of Washington Medical Center, Seattle, WA, USA, Babak Boroojerdi, MD, PhD, MBA, UCB, Manheim, Germany, Petra Duda, MD, PhD, UCB, Cambridge, MA, USA ( at the time of the study), Fiona Grimson, PhD, UCB, Slough, UK, Mark Vanderkelen, MD, UCB, Brussels, Belgium, M. Isabel Leite, MD, DPhil, University of Oxford

Introduction

In the Phase 3, 12-week RAISE study (NCT04115293), zilucoplan significantly improved myasthenia gravis (MG)-specific outcomes versus placebo in patients with acetylcholine receptor autoantibody-positive (AChR Ab+) generalized MG (gMG). This post hoc interim analysis of the open-label extension study, RAISE-XT (NCT04225871) assessed responder rates for Myasthenia Gravis Activities of Daily Living (MG-ADL), Quantitative Myasthenia Gravis (QMG) and Minimal Symptom Expression (MSE) up to 120 weeks.

Methods

RAISE-XT enrolled adults with AChR Ab+ gMG who completed qualifying Phase 2 (NCT03315130) or Phase 3 (NCT04115293) studies. Patients self-administered daily subcutaneous injections of zilucoplan 0.3 mg/kg. From Week 24 (12 weeks into RAISE-XT), patients who received placebo or zilucoplan 0.3 mg/kg in the qualifying studies were assessed as one pooled group. The primary outcome was incidence of treatment-emergent adverse events (TEAEs). Exploratory outcomes included MG-ADL and QMG responder rates (≥3-point and ≥5-point reduction from baseline without rescue therapy, respectively) and MSE response rate (MG-ADL score of 0 or 1 without rescue therapy).

Results

Overall, RAISE-XT enrolled 200 patients (median [range] exposure, 2.2 [0.11–5.6] years at data cut-off [November 11, 2023]); 93 received zilucoplan 0.3 mg/kg in the qualifying studies and in RAISE-XT, and 90 switched from placebo to zilucoplan 0.3 mg/kg. At baseline, MG-ADL, QMG and MSE responder rates were 74.2%, 59.8% and 19.4% for the zilucoplan group (n=93), and 52.2%, 37.1% and 7.8% for the placebo group (n=90), respectively. At Week 120, MG-ADL, QMG and MSE responder rates in the pooled zilucoplan group (n=183) improved to 87.7%, 85.7% and 41.1%, respectively. The most common TEAEs were COVID-19 (n=71/200, 35.5%), MG worsening (n=59/200, 29.5%) and headache (n=44/200, 22.0%). Most TEAEs were not treatment related (93.2%).

Conclusion

MG-ADL, QMG and MSE responder rates were high and sustained up to Week 120 of treatment. Zilucoplan demonstrated a favorable safety profile and was well tolerated.

These data were previously presented at ICNMD, October 25–29, 2024.