Mepolizumab Approved as First Biologic to Treat COPD with Eosinophilic Phenotype

The FDA on Thursday approved mepolizumab (Nucala; GSK) as an add-on maintenance treatment for adult patients with inadequately controlled chronic obstructive pulmonary disease (COPD) and an eosinophilic phenotype, according to a GSK announcement. This approval makes the monoclonal antibody, which targets and binds to interleukin (IL)-5, the only approved biologic studied in a wide COPD population with an eosinophilic phenotype characterized by blood eosinophil count (BEC) starting at 150 cells/μL.1

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The efficacy in individuals with elevated BEC addresses a significant unmet need, as nearly 70% of adults with COPD in the US who remain inadequately controlled on maximal inhaled triple therapy have the phenotype, characterized by recurrent acute exacerbations, often followed by hospitalization.2,3 This represents more than 1 million adults at risk of exacerbations who could potentially benefit from adding mepolizumab to their treatment regimen.2,3

“COPD isn’t just a disease, it’s a relentless cycle. For individuals living with [the disease], managing exacerbations is an ongoing challenge, even with inhaled maintenance therapy. Biologics like mepolizumab are providing renewed optimism," Jean Wright, MD, MBA, chief executive officer of the COPD Foundation, said in the GSK statement.1

The FDA based its decision on data from the MATINEE2 and METREX phase III trials, which demonstrated that mepolizumab significantly reduced the annualized rate of moderate/severe exacerbations (AER) vs placebo in adults with COPD and evidence of type 2 inflammation, ie, BEC of 300 or more cells/μL. In MATINEE, mepolizumab reduced the rate of moderate to severe exacerbations by 21% (rate ratio, 0.79; 95% CI, 0.66 -0.94; P =.01) vs placebo. METREX data revealed similar benefits, with mepolizumab-treated participants experiencing reduction in exacerbations of 18% (RR 0.82; 95% CI, 0.68-0.98; adjusted P =.04).1,2

A predefined secondary endpoint in MATINEE showed mepolizumab reduced the annualized rate of COPD exacerbations requiring emergency department visits and/or hospitalization compared with placebo by 35% (RR 0.65; 95% CI, 0.43- 0.96), though this was not statistically significant due to failure of an endpoint higher in the predefined statistical testing hierarchy, according to GSK.1

"Long-term follow-up studies have demonstrated that exacerbations are the single most important predictor of future risk, with particularly poor outcomes in those requiring hospital visits or admissions," Kaivan Khavandi, GSK SVP and global head, respiratory, immunology & inflammation, said in the statement.1

The MATINEE cohort comprised a broad COPD population including adults with chronic bronchitis, emphysema-only, or both phenotypes, with moderate to very severe disease severity classified according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 2-4.1 Mepolizumab was administered subcutaneously at 100 mg every 4 weeks for 52 to 104 weeks as add-on therapy to treatment with dual long-acting bronchodilators plus inhaled corticosteroid. The full analysis of MATINEE included 403 patients enrolled on the mepolizumab arm and 401 on placebo, all of whom had experienced exacerbations in the previous year despite receiving optimized inhaled maintenance therapy.2

The incidence of adverse events in the clinical trials was similar between placebo and mepolizumab groups, the company said.

The primary treatment goal for adults with COPD is to reduce symptoms and the future risk of exacerbations. The recovery time from an exacerbation varies from person to person but may take up to 6 weeks.5 Some individuals do not return to their previous level of function and there is evidence that an exacerbation causes irreversible lung damage.5

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 23, 2025. https://us.gsk.com/en-us/media/press-releases/nucala-mepolizumab-approved-by-us-fda-for-use-in-adults-with-chronic-obstructive-pulmonary-disease-copd/
2. Halsey G. Mepolizumab reduces AER in COPD leading to emergency care by 35%: MATINEE findings published in NEJM. Patient Care Online. May 1, 2025. https://www.patientcareonline.com/view/mepolizumab-reduces-aer-in-copd-leading-to-emergency-care-by-35-matinee-findings-published-in-nejm
3. Chen S, Miravitlles M, Rhee CK, et al. Patients with chronic obstructive pulmonary disease and evidence of eosinophilic inflammation experience exacerbations despite receiving maximal inhaled maintenance therapy. Int J Chron Obstruct Pulmon Dis. 2022;17:2187–2200. doi:10.2147/COPD.S378649.
4. Müllerová H, et al. Exacerbations and health care resource use among patients with COPD in relation to blood eosinophil counts. Int J Chron Obstruct Pulmon Dis. 2019;14:683-692. doi:10.2147/COPD.S194367
5. Global Initiative for Chronic Obstructive Lung Disease (GOLD). 2025 Gold Report. Accessed May 22, 2025. https://www.goldcopd.org.