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Proteomic Identification of Plasma Biomarkers of Response to IL-5 Inhibitor Biologics in Healthy Subjects.


ABSTRACT: The current project was designed to evaluate the utility of proteomics in identifying pharmacodynamic (PD) biomarkers for IL-5 inhibitors mepolizumab and reslizumab. We profiled over 7,000 plasma proteins from longitudinal samples collected from healthy participants treated with mepolizumab (24 mg, n=8), reslizumab (0.8 mg/kg, n=8), or placebo (n=8), and validated findings at lower doses of mepolizumab (12 mg, n=8) and reslizumab (0.4 mg/kg, n=8). We identified eosinophil major basic protein (EMBP) and proteoglycan-3 (PRG3) as promising plasma PD biomarkers, with EMBP responding to mepolizumab and PRG3 to reslizumab treatment. Both biomarkers demonstrated >20% fold change differences versus placebo, achieved statistical significance, and showed dose-response trends and comparable variability to placebo. Our study identified EMBP and PRG3 as promising plasma PD biomarkers for IL-5 inhibitors, warranting further validation for early phase trials and biosimilar development programs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE311320 | GEO | 2026/02/11

REPOSITORIES: GEO

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