MATINEE Trial Shows Nucala Significantly Reduces COPD Exacerbations in Patients With Eosinophilic Inflammation on Triple Therapy

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Results of the Phase III MATINEE trial (NCT04133909) show that Nucala (mepolizumab) produced a significant reduction in the annualized rate of moderate or severe exacerbations and prolonged time to first exacerbation in patients with eosinophilic chronic obstructive pulmonary disease (COPD) receiving triple inhaled therapy.^1,2 These findings, published by The New England Journal of Medicine, reinforce the role of targeted biologics in personalized therapeutic approaches for COPD with type 2 inflammation, according to the study authors.³

“Every physician will know the feeling of seeing a patient hospitalized due to an exacerbation that could have possibly been prevented,” lead MATINEE trial author Frank Sciurba, professor of Pulmonary, Allergy and Critical Care Medicine, said in a press release. “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.”¹

Nucala is a humanized interleukin (IL)-5 antagonist monoclonal antibody. The drug attaches to IL-5 to stop it from binding to the alpha chain of the IL-5 receptor complex on the eosinophil cell surface. This action inhibits IL-5 signaling to lower the production and survival of eosinophils.⁴

“An estimated 20 to 40% of patients with (COPD) have signs of eosinophilic inflammation, a condition that is characterized by an increased blood eosinophil count,” the study authors wrote. “(IL)-5 is a key type 2 inflammatory cytokine that drives eosinophil differentiation, growth, maturation, migration, and survival in blood and tissues. Alterations resulting from eosinophilic inflammation, including airway remodeling, mucus plugging, and dysregulation of immune responses, are probably important drivers of worsening health and exacerbations in patients with COPD.”³

Nucala has received FDA approvals as an add-on maintenance treatment for patients aged six years and older with severe asthma and with an eosinophilic phenotype; as an add-on maintenance treatment of chronic rhinosinusitis with nasal polyps in patients aged 18 years and older who have not achieved an adequate response to nasal corticosteroids; for the treatment of adults with eosinophilic granulomatosis with polyangiitis; and for the treatment of patients aged 12 years and older with hypereosinophilic syndrome for ≥ six months without an identifiable non-hematologic secondary cause.⁴

Trial Design

The double-blind, randomized, placebo-controlled MATINEE trial enrolled 804 patients with COPD, a history of exacerbations, and a blood eosinophil count of at least 300 cells per microliter who were on triple inhaled therapy. Patients were randomly assigned in a 1:1 ratio to receive Nucala at a dose of 100 mg (n = 403) or placebo (n = 401) subcutaneously every four weeks for 52 to 104 weeks.

The trial’s primary endpoint was annualized rate of moderate or severe exacerbations. Key secondary endpoints included moderate or severe exacerbation as assessed in a time-to-first-event analysis; measures of health-related quality of life and symptoms; and annualized rate of exacerbations causing an emergency department visit, hospitalization, or both.

Results show the annualized rate of moderate or severe exacerbations was 0.80 events per year in the Nucala cohort compared to 1.01 events per year in the placebo cohort (rate ratio, 0.79; 95% confidence interval [CI], 0.66 to 0.94; P=0.01). Time to first moderate or severe exacerbation was 419 days in the Nucala cohort compared to 321 days in the placebo cohort (hazard ratio, 0.77; 95% CI, 0.64 to 0.93; P=0.009).

Investigators did not find significant differences in measures of health-related quality of life, symptoms, and adverse events (AEs) between the two cohorts. The most frequently reported AEs were exacerbation or worsening of COPD, at 12% in the Nucala cohort compared to 15% in the placebo cohort, and COVID-19 infection, occurring in 12% of patients in both cohorts.

“This phase 3 trial showed a significantly lower annualized rate of moderate or severe COPD exacerbations and a longer time to the first exacerbation with mepolizumab than with placebo among patients with COPD, a history of exacerbations, and an eosinophilic phenotype (≥300 cells per microliter) who were receiving background triple inhaled therapy,” the study authors concluded. “Patients were eligible for the trial regardless of the presence or absence of symptoms of chronic bronchitis, the spectrum of disease severity as measured by the FEV1 after albuterol therapy was broad, and many conditions related to COPD were present. These findings indicate that mepolizumab treatment provides additional benefit to patients receiving guideline-based maintenance therapy alone.”³

References

1. 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. Published April 30, 2025. Accessed May 1, 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/

2. Mepolizumab as Add-on Treatment IN Participants With COPD Characterized by Frequent Exacerbations and Eosinophil Level (MATINEE). ClinicalTrials.gov. Updated December 11, 2024. Accessed May 1, 2025. https://clinicaltrials.gov/study/NCT04133909

3. Sciurba F., et al. Mepolizumab to Prevent Exacerbations of COPD with an Eosinophilic Phenotype. N Engl J Med 2025;392:1710-1720. DOI: 10.1056/NEJMoa2413181. Vol. 392 No. 17.

4. Nucala prescribing information. NUCALA (mepolizumab) for injection NUCALA (mepolizumab) injection (gskpro.com). https://nucalahcp.com/. Accessed May 1, 2025.