FDA Approves Mepolizumab as Add-On Treatment for COPD

On May 22, 2025, the US Food and Drug Administration approved mepolizumab (Nucala; GSK) as add-on maintenance treatment for adult patients with poorly controlled chronic obstructive pulmonary disease (COPD) with an eosinophilic phenotype.

Mepolizumab is a monoclonal antibody that targets interleukin-5 (IL-5), a key cytokine driving type 2 inflammation. It is now the only approved biologic for patients with COPD with an eosinophilic phenotype defined by a blood eosinophil count (BEC) ≥150 cells/µL.

The FDA approved mepolizumab for eosinophilic COPD based on the MATINEE and METREX trials, which showed it significantly reduced moderate to severe exacerbations versus placebo. These benefits were observed across a many patients with elevated blood eosinophil counts.

The MATINEE and METREX trials are phase 3, randomized (1:1), double-blind, parallel-group studies evaluating the efficacy and safety of mepolizumab 100 mg given subcutaneously every 4 weeks. Mepolizumab was used as an add-on to optimized inhaled triple therapy, which included dual long-acting bronchodilators and an inhaled corticosteroid, compared with placebo.

In both the MATINEE and METREX trials, mepolizumab significantly reduced the annual rate of moderate or severe exacerbations compared to placebo in patients with an eosinophilic phenotype receiving triple inhaled therapy (MATINEE: rate ratio [RR], 0.79; 95% CI, 0.66-0.94; P=0.01; METREX: RR, 0.82; 95% CI, 0.68-0.98; adjusted P=0.04).

In the MATINEE trial, a pre-specified secondary analysis showed that mepolizumab reduced the annualized rate of COPD exacerbations requiring emergency department visits or hospitalization compared with placebo (RR, 0.65; 95% CI, 0.43-0.96). However, this result was not considered statistically significant due to the failure of an earlier endpoint in the trial’s predefined statistical hierarchy.

In the US, around 70% of COPD patients who remain uncontrolled on inhaled triple therapy and continue to experience exacerbations have a BEC ≥150 cells/μL. This equates to over one million individuals at increased risk for exacerbations, including those resulting in emergency department visits or hospitalizations, who may benefit from adding mepolizumab to their treatment regimen.