Maintenance of zilucoplan efficacy in patients with generalised myasthenia gravis up to 24 weeks: a model-informed analysis.

Autor:	de la Borderie G; UCB, 420 rue d'Estienne d'Orves, Colombes 92700, France., Chimits D; UCB, Colombes, France., Boroojerdi B; UCB, Monheim, Germany., Brock M; UCB, Morrisville, NC, USA., Duda PW; UCB, Cambridge, MA, USA., Grimson F; UCB, Slough, UK., Mahoney P; UCB, Slough, UK., Strimenopoulou F; UCB, Slough, UK., Cutter G; Department of Biostatistics, The University of Alabama at Birmingham School of Public Health, Birmingham, AL, USA., Aban I; Department of Biostatistics, The University of Alabama at Birmingham School of Public Health, Birmingham, AL, USA., Brauner S; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.; Department of Neurology, Karolinska University Hospital, Stockholm, Sweden., Petersson M; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden., Howard JF Jr; Department of Neurology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Bennett N; UCB, Morrisville, NC, USA.
Jazyk:	angličtina
Zdroj:	Therapeutic advances in neurological disorders [Ther Adv Neurol Disord] 2024 Sep 21; Vol. 17, pp. 17562864241279125. Date of Electronic Publication: 2024 Sep 21 (Print Publication: 2024).
DOI:	10.1177/17562864241279125
Abstrakt:	Background: Clinical efficacy of zilucoplan has been demonstrated in a 12-week, placebo-controlled, phase III study in patients with acetylcholine receptor autoantibody-positive generalised myasthenia gravis (gMG). However, placebo-controlled zilucoplan data past 12 weeks are not available. Objectives: Predict the treatment effect of zilucoplan versus control (placebo or standard of care) in patients with gMG up to 24 weeks. Design: A model-informed analysis (MIA) within a Bayesian framework. Methods: Part 1 of the MIA comprised a control meta-regression using aggregate data on control response over time from randomised studies and a national myasthenia gravis (MG) registry. In Part 2, a combined Bayesian analysis of individual patient-level data from the phase II (NCT03315130), RAISE (NCT04115293) and RAISE-XT (NCT04225871) studies of zilucoplan was conducted using posterior distributions from Part 1 as informative priors. Population mean treatment effect in the change from baseline (CFB) at week 24 in MG-Activities of Daily Living (MG-ADL) and quantitative MG (QMG) scores for zilucoplan versus control were assessed. Results: At week 24, the predicted mean CFB in MG-ADL score was -4.55 (95% credible interval: -6.04, -3.13) with zilucoplan versus -2.00 (-3.35, -0.64) with control (difference: -2.55 [-3.76, -1.40]). The probability of a favourable treatment effect as measured by MG-ADL score at week 24 with zilucoplan versus control was >99.9%. There was an 82.8% probability that the difference in the predicted mean CFB in MG-ADL score at week 24 was greater than the clinically meaningful threshold (⩾2.0-point improvement). Comparable results were observed with QMG. Conclusion: This MIA demonstrates the maintenance of efficacy with zilucoplan versus control up to 24 weeks. Through combining real-world evidence with data from randomised studies, this novel method to estimate long-term treatment efficacy facilitated reduced exposure to placebo in the phase III RAISE study. This methodology could be used to reduce the length of future placebo-controlled studies. (© The Author(s), 2024.)
Databáze:	MEDLINE
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