Improvement of Ocular Subdomain Scores With Zilucoplan in Patients With Generalized Myasthenia Gravis in the RAISE and RAISE-XT Studies

Topic:

Clinical Trials

Poster Number: 224 M

Author(s):

M. Isabel Leite, MD, FRCP, DPhil, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK, Saskia Bresch, MD, Service de Neurologie, Hospital Pasteur, Centre Hospitalier Universitaire de Nice, Nice, France, Miriam Freimer, MD, Ohio State University, Channa Hewamadduma, MBBS, 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, Kimiaki Utsugisawa, Hanamaki General Hospital, Babak Boroojerdi, MD, PhD, MBA, UCB, Monheim, Germany, Fiona Grimson, PhD, UCB, Slough, UK, Natasa Savic, MD, PhD, UCB, Bulle, Switzerland, James F. Howard Jr., MD, University of North Carolina

Introduction

Ocular symptoms in gMG impact the daily activities of patients. RAISE (NCT04115293), a Phase 3, double-blind, placebo-controlled study of zilucoplan, a complement component 5 inhibitor, demonstrated clinically meaningful improvements in MG-ADL and QMG total scores in patients with AChR Ab+ gMG.

Objective

To evaluate the effect of zilucoplan on MG-ADL and QMG ocular symptoms in patients with gMG in RAISE and RAISE-XT (NCT04225871), an ongoing, Phase 3, open-label extension study.

Methods

In RAISE, adults with AChR Ab+ gMG were randomized 1:1 to once-daily subcutaneous zilucoplan 0.3 mg/kg or placebo self-injections for 12 weeks. Adults who completed RAISE or a Phase 2 study (NCT03315130) entered RAISE-XT to receive zilucoplan 0.3 mg/kg. The primary outcome of RAISE-XT was incidence of treatment-emergent adverse events (TEAEs). We assessed (post hoc) change from baseline (CFB) in MG-ADL and QMG ocular subdomain scores at Week 12 of RAISE and Week 120 of RAISE-XT in patients with baseline scores ≥1 in that subdomain. Ocular subdomains in MG-ADL and QMG both assess ptosis and diplopia, with QMG additionally assessing facial muscles. A decrease in score indicates an improvement in these symptoms.

Results

At Week 12 of RAISE, mean (standard error [SE]) CFB in MG-ADL ocular subdomain scores was −1.53 (0.19) for zilucoplan (n=79) and −0.86 (0.17) for placebo (n=83). For QMG, mean (SE) CFB was −2.05 (0.24) for zilucoplan (n=80) and −1.27 (0.24) for placebo (n=82). At Week 120 of RAISE-XT, mean (SE) CFB was −1.37 (0.27; n=41) and −2.52 (0.30; n=52) for MG-ADL and QMG ocular subdomain scores, respectively. TEAEs occurred in 97.0% (n=194/200) of patients (interim data cut-off: 11 November 2023).

Summary/conclusion

Treatment with zilucoplan led to improvements in MG-ADL and QMG ocular subdomain scores that were sustained through to Week 120, supporting the use of zilucoplan in patients with ocular symptoms.