The Mepolizumab as Add-on Treatment IN Participants With COPD Characterized by Frequent Exacerbations and Eosinophil Level (MATINEE) trial of mepolizumab showed statistically and clinically significant reductions in the annualized rate of moderate to severe exacerbations compared with placebo for patients with COPD and type 2 inflammation with elevated serum eosinophils. The two-year trial showed no change in adverse events between the mepolizumab and placebo groups.¹

Based on the trial data, the US Food and Drug Administration (FDA) approved mepolizumab for patients with COPD on May 22.

“We now have a second agent in our arsenal for patients with high type 2 inflammation,” said Frank Sciurba, MD, FCCP, Professor of Medicine and Education and Director of the Emphysema/COPD Research Center and Pulmonary Function Exercise Physiology Laboratory at the University of Pittsburgh Medical Center. “The first is dupilumab, which targets a different receptor. As we get smarter, we will know whether some patients are more responsive to one than the other.”

MATINEE is unique in that the trial was interrupted by the COVID-19 pandemic. Thus, it became the longest-ever trial of a biologic in COPD, said Gerard J. Criner, MD, FCCP, Chair and Professor of Thoracic Medicine and Surgery at the Lewis Katz School of Medicine at Temple University and Director of the Temple Lung Center.

“That is one of the few bright sides of COVID-19; it extended the trial to 104 weeks and allowed MATINEE to show a very significant reduction in the primary outcome of severe exacerbations—21%— and delayed the onset of moderate to severe exacerbations by three months,” Dr. Criner said. “And there was no increase in risk in terms of serious adverse events compared with placebo in the trial.”

Mepolizumab was originally developed to treat asthma, and MATINEE was specifically designed to answer FDA questions about its use for the treatment of COPD following the METREX (MEpolizumab vs. placebo as add‐on TReatment for frequently EXacerbating COPD patients) and METREO (MEpolizumab vs. placebo as add‐on TReatment for frequently exacerbating COPD patients characterized by EOsinophil level) trials in 2017.² The MATINEE trial design rigorously excluded patients with any prior diagnosis of asthma to eliminate the risk of asthma being a confounding variable.

“Even if you had a patient with no allergic symptoms [and] no dramatic bronchodilator reversibility who smoked heavily and had eosinophils at 450 cells/μL with no respiratory symptoms until their 60s, but their primary care provider once suggested maybe this person had asthma, that person was excluded,” he said.

MATINEE randomized 804 patients with COPD, a history of exacerbations, and a blood eosinophil count of at least 300 cells/μL; 403 to mepolizumab and 401 to placebo. All patients were on triple inhaled therapy.

The primary end point was the annualized rate of moderate or severe exacerbations. Secondary end points included time to first exacerbation, health-related quality of life, and the annualized rate of exacerbations leading to an emergency department visit and/or hospitalization.

The rate ratio for exacerbations was 0.79 (95% CI, 0.66-0.94; P = .01) favoring mepolizumab. The time to first moderate or severe exacerbation was 419 days vs 321 days, with a hazard ratio of 0.77 (95% CI, 0.65-0.02; P = .0009).

Dr. Criner noted that patient-reported health-related quality of life scores were numerically better for mepolizumab but not statistically significant. The mepolizumab group also had a numerically lower annualized rate of exacerbations resulting in an emergency department visit and/or hospitalization.

“Assuming payers support mepolizumab in the same way they’re supporting dupilumab, there should be no reason in a [patient with frequent exacerbations] with high eosinophils not to consider one of these drugs,” Dr. Sciurba said. “But type 2 inflammation only represents 20% to 40% of all patients. We need to identify precision therapies [that] target the other 60% to 80% as well.”

1. Sciurba FC, Criner GJ, Christenson SA, et al. Mepolizumab to prevent exacerbations of COPD with an eosinophilic phenotype. N Engl J Med. 2025;392(17):1710-1720. doi:10.1056/NEJMoa2413181

2. Pavord ID, Chanez P, Criner GJ, et al. Mepolizumab for eosinophilic chronic obstructive pulmonary disease. N Engl J Med. 2017;377(17):1613-1629. doi:10.1056/NEJMoa1708208