Response over time with zilucoplan in generalized myasthenia gravis: Post hoc analysis of RAISE-XT 60-week follow up

Topic:

Clinical Trials

Poster Number: P357

Author(s):

Channa Hewamadduma, MBS, FRCP (Neuro), FRCPE, PhD, Academic Neuroscience Unit, Sheffield Teaching Hospitals NHS FT, and SITraN, Univ. of Sheffield, UK, Saskia Bresch, MD, Service de Neurologie, Hospital Pasteur, Centre Hospitalier Universitaire de Nice, Nice, France, Miriam Freimer, MD, Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, USA, M. Isabel Leite, MD, DPhil, University of Oxford, Angelina Maniaol, PhD, Department of Neurology, Oslo University Hospital, Oslo, Norway, Kimiaki Utsugisawa, MD, PhD, Hanamaki General Hospital, Raphaëlle Beau Lejdstrom, PhD, UCB, Bulle, Switzerland, Babak Boroojerdi, MD, PhD, MBA, UCB, Manheim, Germany, Fiona Grimson, PhD, UCB, Slough, UK, Natasa Savic, MD, PhD, UCB, Bulle, Switzerland, James F. Howard Jr., MD, University of North Carolina

Introduction

In an interim analysis of RAISE-XT (NCT04225871), an ongoing open-label extension (OLE) study, zilucoplan, a macrocyclic peptide complement component 5 inhibitor, showed sustained and clinically meaningful improvements in myasthenia gravis-specific outcomes in patients with acetylcholine receptor autoantibody-positive generalized myasthenia gravis (gMG). In this post hoc analysis, we assessed the long-term outcomes of Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) responders or non-responders at Week 12 of a qualifying, double-blind study (Phase 2, NCT03315130 or Phase 3, NCT04115293).

Methods

Eligible adults with gMG self-administered daily subcutaneous injections of zilucoplan 0.3 mg/kg in RAISE-XT. MG-ADL and QMG responder rates (≥3-point and ≥5-point reductions from double-blind baseline without rescue therapy, respectively) were exploratory endpoints.

Results

Of 93 patients randomized to zilucoplan 0.3 mg/kg in the double-blind studies, 74.2% (n=69/93) were MG-ADL and 59.8% (n=55/92) were QMG responders at Week 12. Among Week 12 responders, responder rates were >88% for MG-ADL and >90% for QMG throughout the OLE up to Week 60. Among Week 12 non-responders, 50.0% (12/24) were MG-ADL responders and 47.2% (17/36) were QMG responders at Week 14. At Week 60, 42.9% (6/14) and 47.8% (11/23) of Week 12 non-responders were MG-ADL and QMG responders, respectively.

Conclusion

Most patients on zilucoplan were responders at Week 12 of the double-blind studies and, among them, responder rates remained high (>88%) throughout the OLE up to Week 60. Of patients who were non-responders at Week 12, approximately half became responders during the OLE, suggesting the benefit of continuing zilucoplan treatment beyond Week 12.

These data were previously presented at EAN, June 29–July 2, 2024.