Clinical trial design of biologic therapies in COPD: MATINEE study of mepolizumab

<bold>Background:</bold> The Phase 3 METREX/METREO trials (<ext-link>NCT02105948</ext-link>/NCT02105961) were the first to show efficacy of anti-IL-5 biologic therapy in patients with COPD who exacerbate despite maximal inhaled triple therapy (ITT). In both trials, patients had clinically meaningful reductions in annual moderate/severe exacerbation rates (AER; 18–20%) with mepolizumab vs placebo (PBO), which were statistically significant in METREX only after multiplicity adjustment. <bold>Aims and Objectives:</bold> Assess efficacy and safety of mepolizumab in COPD with Type 2 inflammation characterised by an eosinophilic phenotype. <bold>Methods:</bold> MATINEE (<ext-link>NCT04133909</ext-link>) is a randomised, double-blind, Phase 3 study of mepolizumab 100 mg (SC) vs PBO (1:1) Q4W for ≥52 weeks (up to 104 weeks) with baseline-optimised ITT. Eligible patients are ≥40 years of age with COPD for ≥1 year (including chronic bronchitis and/or emphysema), no history of asthma, blood eosinophil counts (BEC; cells/µL) ≥300 at screening AND ≥150 1 year prior or at Visit 1, and ≥2 moderate or ≥1 severe exacerbations in the past year despite ITT. BEC criteria were informed by a pre-specified METREX/METREO meta-analysis, in which mepolizumab significantly reduced AER vs PBO by 18% and demonstrated greater efficacy in patients with higher BEC at screening (BEC AER reduction vs PBO]: ≥150 [16%]; ≥300 [24%]). Current/former smokers with past (but not current) asthma diagnosis were eligible in METREX/METREO but not MATINEE. <bold>Conclusions:</bold> METREX and METREO pioneered the development of biologic therapies for COPD and supported phenotype characterisation, informing the study design of future biologic trials for this disease, including the ongoing MATINEE trial.