FDA Approves Mepolizumab for Treatment of Patients With COPD and an Eosinophilic Phenotype

Mepolizumab (Nucala; GSK) received FDA approval as an add-on maintenance treatment for adult patients with inadequately controlled chronic obstructive pulmonary disorder (COPD) and an eosinophilic phenotype. The decision is based on data from the MATINEE (NCT04133909) and METREX (NCT02105948) phase 3 trials, which showed a promising reduction in the annualized rates of moderate or severe exacerbations with mepolizumab.^1,2

Visualization of human body with COPD highlighted on lungs | Image Credit: © Lila Patel - stock.adobe.com

COPD is a progressive, heterogeneous inflammatory lung disease that affects over 390 million individuals around the globe. The disease, which includes conditions such as chronic bronchitis and/or emphysema, is primarily characterized by persistent respiratory symptoms such as breathlessness, cough, and sputum, along with progressive airflow obstruction due to the chronic inflammation. These symptoms have a significant impact on daily quality of life, underscoring the need for advanced therapeutic options.³

Standard treatment is inhaled triple therapy; however, many patients still experience persistent and/or exacerbated symptoms, which can be acute episodes of worsening COPD. In severe cases, COPD symptoms can lead to hospitalization, irreversible lung damage, and mortality.³

“COPD isn’t just a disease, it’s a relentless cycle,” Jean Wright, MD, MBA, chief executive officer of the COPD Foundation, explained in a press release. “For individuals living with COPD, managing exacerbations is an ongoing challenge, even with inhaled maintenance therapy. Biologics like mepolizumab are providing renewed optimism for those affected by COPD.”³

Mepolizumab is a monoclonal antibody that selectively targets and binds to the key messenger protein responsible for type 2 inflammation: interleukin-5 (IL-5). It was developed to treat a variety of IL-5–mediated diseases and is approved in both Europe and the United States for multiple indications. The FDA approval for mepolizumab for patients with COPD is based on positive data from the MATINEE and METREX trials.³

MATINEE and METREX are both phase 3 randomized, double-blind, parallel-group trials assessing the efficacy and safety of mepolizumab at a dosage of 100 mg as add-on therapy, administered subcutaneously every 4 weeks compared with placebo and optimal inhaled triple therapy. In MATINEE, investigators assessed the efficacy and safety of mepolizumab for 52 to 104 weeks in 804 patients with COPD with evidence of type 2 inflammation. The METREX trial was dedicated to evaluating the safety and efficacy of mepolizumab for 52 weeks in 836 patients.³

In both trials, mepolizumab significantly reduced the annualized rate of moderate or severe exacerbations compared with placebo in patients with an eosinophilic phenotype. In MATINEE, the rate ratio (RR) was 0.79 (95% CI, 0.66–0.94; P = .01), whereas in METREX, the RR was 0.82 (95% CI, 0.68–0.98; adjusted P = .04). The secondary end point in MATINEE—the reduction in annualized rate of COPD exacerbations requiring emergency department visits or hospitalization—was reduced in the mepolizumab group compared with placebo (RR, 0.65; 95% CI, 0.43–0.96). However, this result was not considered statistically significant due to the failure of an earlier endpoint in the pre-specified hierarchical testing strategy.³

“The approval of Nucala in the US provides an important option for COPD patients,” Kaivan Khavandi, SVP, global head, Respiratory, Immunology & Inflammation R&D, GSK, said in a press release. “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. Today there is hope for improved care for COPD patients with an eosinophilic phenotype, including those with a BEC threshold as low as [less than or equal to] 150 cells/μL who need new options like Nucala to support their treatment journey.”³

REFERENCES

1. Mepolizumab as add-on treatment in participants With COPD characterized by frequent exacerbations and eosinophil level (MATINEE). Updated December 11, 2024. Accessed May 22, 2025. https://clinicaltrials.gov/study/NCT04133909

Study to evaluate efficacy and safety of mepolizumab for frequently exacerbating chronic obstructive pulmonary disease (COPD) patients. Updated August 31, 2018. Accessed May 22, 2025. https://clinicaltrials.gov/study/NCT02105948

3. Nucala (mepolizumab) approved by US FDA for use in adults with chronic obstructive pulmonary disease (COPD). GSK. May 22, 2025. Accessed May 22, 2025. https://www.gsk.com/en-gb/media/press-releases/nucala-mepolizumab-approved-by-us-fda/