Newly Approved Mepolizumab Mitigates COPD Exacerbations

Adding mepolizumab to inhaled triple therapy significantly improved exacerbation outcomes compared with placebo in adults with chronic obstructive pulmonary disease (COPD), based on data from the MATINEE study presented at the American Thoracic Society (ATS) 2025 International Conference.

Based on these findings, mepolizumab is newly approved by the US Food and Drug Administration for the treatment of COPD according to manufacturer GlaxoSmithKline.

“This decision is good news for patients because it allows more options for care, and it is good news for the future of COPD treatment in that there are now more options showing targets previously not identified that can improve patient outcomes,” said co-author Gerard J. Criner, MD, of the Lewis Katz School of Medicine at Temple University, Philadelphia, in a statement following the approval.

Patients with COPD and type 2 inflammation are at an increased risk for frequent and severe exacerbations that may require hospitalization or emergency department visits, Alberto Papi, MD, of the University of Ferrara, Ferrara, Italy, and colleagues wrote in their abstract.

Mepolizumab, a humanized monoclonal antibody that targets interleukin-5 (IL-5), significantly reduced COPD exacerbations in patients with COPD regardless of the history or severity of exacerbations in a phase 3 study known as MATINEE, the researchers wrote.

In the study, the researchers randomized 804 adults aged 40 years or older with COPD to a subcutaneous dose of 100 mg of mepolizumab every 4 weeks for 52-104 weeks, or a placebo, in addition to the inhaled triple therapy of a fluticasone propionate dose of at least 500 μg/d or the equivalent, plus dual long-acting bronchodilators. Approximately 21% of the patients had a history of severe exacerbations in the past years. The mean age of the participants was approximately 66 years, and at least two thirds were men.

Overall, patients treated with mepolizumab had a 21% reduced annualized rate of moderate to severe exacerbations compared with patients treated with placebo, with rate ratios of 0.75 and 0.79 for subgroups with and without a history of severe exacerbations, respectively.

In addition, patients with a history of severe exacerbations had a 32% reduced rate of exacerbations requiring an emergency department visit or hospital stay.

The results were durable as well, the researchers noted. The significant difference in exacerbation rates between patients treated with mepolizumab and those treated with placebo was observed at 1 year and continued for up to 104 weeks of treatment.

The incidence of adverse events and serious adverse events was similar in the mepolizumab and placebo groups, the most common of which was exacerbation of COPD (11% and 15% for serious adverse events in the mepolizumab and placebo groups, respectively).

Takeaways and Next Steps

The researchers were surprised that mepolizumab’s significant clinical impact on exacerbation reduction extended to such a broad group of patients with COPD, including those who did or did not have chronic bronchitis, and those with evidence of emphysema, Criner said in an interview. “That mepolizumab could decrease emergency room visits and hospitalization is a significant benefit for patients,” he added.

Mepolizumab made all its primary and key secondary end points with a robust safety profile, said Criner. “Patients with COPD who have type 2 inflammation can benefit from biologic therapy, regardless of the severity of underlying airflow obstruction with or without the absence of chronic bronchitis or emphysema to reduce moderate and severe exacerbations,” he said.

Additional research should target different pathways and patients who have inflammation with COPD, such as types 1 and 3, Criner noted.

Approval Sparks Enthusiasm

“I’m excited to have another option to treat COPD patients who have elevated eosinophils and frequent exacerbations,” said study co-author Meilan Han, MD, of the University of Michigan, Ann Arbor, Michigan, in an interview. “I’d like additional research to help us understand which patients experience the best response in terms of lung function and symptoms,” she added.

The approval will change care of patients with COPD who are already maximized on inhaler therapies and continue to have exacerbations, “as this is the only biologic approved for patients with blood eosinophils <= 300 cells/µL,” said Arianne K. Baldomero, MD, a pulmonologist and assistant professor of medicine at the University of Minnesota, Minneapolis, in an interview. “The cost could be prohibitive (annual cost is almost $50,000 per year); so patients should explore insurance coverage, manufacturer assistance programs, nonprofit financial support, and discount cards to reduce their out-of-pocket expenses for mepolizumab,” she said.

“The MATINEE study was important because, despite optimal triple inhaler therapy, many high-risk patients continue to experience frequent COPD exacerbations. This trial evaluated whether adding a new therapy can further reduce exacerbations in this high-risk COPD population,” said Baldomero.

However, as with other biologics, when or whether mepolizumab can be safely discontinued, and whether the risk for COPD exacerbations will return upon stopping remains unclear, said Baldomero. “Additionally, there is limited evidence to guide whether inhaler therapies can be withdrawn while on biologics, and more research is needed to determine optimal treatment duration,” she said.

Expanded MATINEE Findings Offer More Insights 

Several other studies of MATINEE findings were presented at the meeting. In one study, data showed that mepolizumab reduced exacerbations in patients with cardiovascular comorbidities compared with placebo.

Post hoc analyses of data from the MATINEE study also were presented at the meeting to examine the effectiveness of mepolizumab in various subgroups. In one post hoc analysis, patients treated with mepolizumab had lower mean healthcare resource use per exacerbation in terms of emergency department visits, urgent care/outpatient clinic visits, and days in intensive care than patients treated with placebo.

Another analysis of MATINEE study data showed that, compared with placebo, mepolizumab significantly improved exacerbation rates in patients with severely restricted airflow based on the GOLD criteria.

An additional post hoc analysis showed that, compared with placebo, mepolizumab’s association with improved exacerbation rates was consistent regardless of duration of COPD.

Mepolizumab has been developed for the treatment of a range of IL-5 mediated diseases associated with type 2 inflammation and is also approved for use in the United States and Europe for severe asthma, eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome, and chronic rhinosinusitis with nasal polyps, according to manufacturer GlaxoSmithKline.

The MATINEE study was funded by GlaxoSmithKline.

Criner disclosed receiving consulting fees and research funds from GlaxoSmithKline.

Han disclosed serving as a consultant for GlaxoSmithKline and multiple relationships with pharmaceutical companies outside of the MATINEE study.

Baldomero had no financial conflicts to disclose.