High Proportion of Zilucoplan Responders Identified in Secondary Analysis of RAISE Trial


After 12 weeks of treatment with zilucoplan 0.3 mg/kg, almost three-fourths of patients demonstrated at least a 3-point reduction in Myasthenia Gravis Activities of Daily Living scores.

James F. Howard, MD, Distinguished Professor of Neuromuscular Disease, and chief, Neuromuscular Disorders Section, University of North Carolina School of Medicine

James F. Howard, MD

In a new analysis of the phase 3 RAISE study (NCT04115293), patients with generalized myasthenia gravis (gMG) treated with zilucoplan (UCB Pharma) showed statistically significant improvements on all key outcomes, including a secondary analysis that evaluated responder rates on Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) score. The findings were presented at the 2022 American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) annual meeting, September 21-24, in Nashville, Tennessee.1

Responders were considered patients who achieved a reduction of at least 3 points on MG-ADL or at least 5 points on QMG without rescue therapy. Between the treated groups, 73.8% of those on zilucoplan 0.3 mg/kg were considered responders on MG-ADL compared with 47.1% of those on placebo (odds ratio [OR], 3.182; 95% CI, 1.660-6.098). Similarly, 59.0% of those on active drug and 33.3% of placebo-treated patients showed at least a 5-point reduction in QMG (P <.001).

Lead trial investigator James F. Howard, MD, Distinguished Professor of Neuromuscular Disease, and chief, Neuromuscular Disorders Section, University of North Carolina School of Medicine, and colleagues randomly assigned adults with MG to either zilucoplan or placebo for 12 weeks, with changes in MG-ADL score as the primary end point. Zilucoplan, a self-administered subcutaneous C5 inhibitor, is still in clinical development for gMG, with a regulatory submission expected to come later this year.

In addition to determining clinical benefit, investigators sought to determine if complement inhibition was effective across patients with acetylcholine receptor (AChR) antibody positive MG, regardless of prior treatment or response to other previous therapies or disease duration. After 12 weeks of treatment, least-squares mean in change from baseline on MG-ADL showed significant improvements with zilucoplan, as demonstrated by changes of –4.42 (95% CI, –5.31 to –3.53) vs –2.30 (95% CI, –3.17 to –1.43) for those on placebo.

The analysis presented at AANEM also showed no unexpected safety features, as the most common treatment-emergent adverse events (AEs) were injection-site bruising (zilucoplan: 16.3%; placebo: 9.1%) and headache (zilucoplan: 15.1% and placebo: 15.9%). In total, 4.7% and 2.3% of those, respectively, on active and placebo drug discontinued because of treatment-emergent AEs.

UCB also has another agent in development, rozanolixizumab, for the treatment of adults with gMG. A subcutaneous-infused monoclonal antibody that targets the neonatal Fc receptor, rozanolixizumab performed well in a recently announced phase 3 study called MycarinG (NCT03971422). In that 66-patient trial, treatment with the study drug resulted in significant reductions of MG-ADL compared with placebo in patients with AChR or muscle-specific tyrosine kinase autoantibody positive generalized MG. All told, in the rozanolixizumab 7- and 10-mg/kg dose groups, investigators observed a placebo-corrected mean improvement of 2.586 and 2.619 points in the MG-ADL relative to placebo (both, <.001).2

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1. Vu T, Genge A, Hussain Y, et al. Efficacy and safety of zilucoplan in myasthenia gravis: responder analysis from the randomized phase 3 RAISE trial. Presented at: 2022 AANEM Annual Meeting; September 21-24; Nashville, TN. Abstract 200.
2. UCB presents efficacy and safety results for zilucoplan and rozanolixizumab in generalized myasthenia gravis. News release. UCB Pharma. May 10, 2022. Accessed September 20, 2022. https://www.ucb-usa.com/stories-media/UCB-U-S-News/detail/article/ucb-presents-efficacy-and-safety-results-for-zilucoplan-and-rozanolixizumad-in-generalized-myasthenia-gravis
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