FDA Approves Mepolizumab as First Once-Monthly Biologic for COPD With Eosinophilic Phenotype

The FDA approved mepolizumab (Nucala; GSK) today as an add-on maintenance treatment for adult patients with inadequately controlled chronic obstructive pulmonary disease (COPD) and an eosinophilic phenotype.¹

Mepolizumab is a monoclonal antibody that targets IL-5, a cytokine with a central role in eosinophilic inflammation, which is present in 20% to 40% of patients with COPD. This approval makes it the first biologic with once-monthly dosing approved for this patient population and marks its fifth indication in the US.

“The approval of Nucala in the US provides an important option for COPD patients," Kaivan Khavandi, senior vice president, global head of respiratory, immunology, and inflammation research and development at GSK, said in a press release. "...Today, there is hope for improved care for COPD patients with an eosinophilic phenotype, including those with a BEC [blood eosinophil count] threshold as low as ≥150 cells/μL who need new options like Nucala to support their treatment journey.”

Mepolizumab is also approved to treat patients 6 years and older with severe eosinophilic asthma, adults with eosinophilic granulomatosis with polyangiitis, and those 12 years and older with hypereosinophilic syndrome. In addition, it is approved as an add-on maintenance treatment for adults with chronic rhinosinusitis with nasal polyps.

This most recent approval was supported by positive phase 3 METREX (NCT02105948) and MATINEE (NCT04133909) trial results. Published in the New England Journal of Medicine in 2017, the METREX trial evaluated the efficacy and safety of mepolizumab over 52 weeks in 836 patients randomized 1:1 to receive either mepolizumab or placebo.²

Patients were stratified into 2 groups based on phenotype: the eosinophilic phenotype group (patients with a blood eosinophilic count of at least 150 cells per microliter at study entry or at least 300 cells per microliter within the past year) and the noneosinophilic phenotype group (patients with a blood eospinophilic count below 150 cells per microliter at study entry and with no evidence of at least 300 cells per microliter in the past year).

In patients with COPD and an eosinophilic phenotype, mepolizumab added to triple inhaled therapy significantly reduced the annualized rate of moderate or severe exacerbations compared with placebo (rate ratio, 0.82; 95% CI, 0.68-0.98; adjusted P = .04).

Results from the MATINEE trial were published more recently, on April 30, in the New England Journal of Medicine, and were also presented earlier this week at the American Thoracic Society 2025 International Conference in San Francisco.^3,4 In the trial, patients with COPD who were receiving triple inhaled therapy, had a history of exacerbations, and a blood eosinophil count of at least 300 cells/μL were assigned 1:1 to receive either 100 mg of mepolizumab or a placebo subcutaneously every month for 52 to 104 weeks.³

The primary end point was the annualized rate of moderate or severe COPD exacerbations. Secondary end points included the time to a patient’s first moderate or severe exacerbation, measures of health-related quality of life and symptoms, and the annualized rate of exacerbations resulting in an emergency department visit, hospitalization, or both.

A total of 403 patients were assigned to receive mepolizumab and 401 to placebo. The trial met its primary end point, with patients receiving mepolizumab showing a 21% reduction in annualized moderate or severe exacerbations compared with placebo (0.80 vs 1.01 events per year; rate ratio, 0.79; 95% CI, 0.66-0.94; P = .01). Additionally, the time to a patient’s first moderate or severe exacerbation was longer in the mepolizumab group (median time to first exacerbation, 419 vs 321 days; HR, 0.77; 95% CI, 0.64-0.93; P = .009).

Adverse event rates were similar between groups (mepolizumab vs placebo, 74% vs 77%), with the most frequent being the exacerbation or worsening of COPD (mepolizumab vs placebo, 12% vs 15%) and COVID-19 infection (12% in both groups). However, between-group differences in measures of health-related quality of life and symptoms were not significant.

Overall, the researchers concluded that adding mepolizumab to background triple inhaled therapy reduced the annualized rate of moderate or severe exacerbations in patients with COPD and an eosinophilic phenotype.

“Every physician will know the feeling of seeing a patient hospitalized due to an exacerbation that could have possibly been prevented,” Frank Sciurba, lead investigator of the MATINEE trial, said in a press release.⁵ “The MATINEE trial uncovers new possibilities in the treatment landscape for COPD patients with type 2 inflammation, as we strive to target drivers of disease and improve the lives of patients suffering with COPD.”

References

1. Nucala (mepolizumab) approved by US FDA for use in adults with chronic obstructive pulmonary disease (COPD). News release. GSK; May 22, 2025. Accessed May 22, 2025. https://www.gsk.com/en-gb/media/press-releases/nucala-mepolizumab-approved-by-us-fda/
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
3. 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
4. Klein H. Mepolizumab reduces COPD exacerbations in patients with eosinophilic inflammation. AJMC^®. May 20, 2025. Accessed May 22, 2025. https://www.ajmc.com/view/mepolizumab-reduces-copd-exacerbations-in-patients-with-eosinophilic-inflammation
5. Nucala (mepolizumab) delivers clinically meaningful and statistically significant reduction in COPD exacerbations, with positive MATINEE trial results published in New England Journal of Medicine. News release. GSK; April 30, 2025. Accessed May 6, 2025. https://www.gsk.com/en-gb/media/press-releases/nucala-mepolizumab-delivers-clinically-meaningful-and-statistically-significant-reduction-in-copd-exacerbations-with-positive-matinee-trial-results-published-in-nejm/