Mepolizumab reduces exacerbations in COPD with type 2 inflammation
Therapy is approved as Nucala for rare ANCA-associated vasculitis type
Adding GSK’s mepolizumab to standard inhaled treatment reduces the frequency of moderate to severe exacerbations in chronic obstructive pulmonary disease (COPD) patients with type 2 inflammation, which contributes to lung inflammation.
That’s according to top-line data from a Phase 3 clinical trial called MATINEE (NCT04133909) announced by GSK in a company press release. The study tested mepolizumab against a placebo in adults with COPD and type 2 inflammation, which is marked by high blood counts of eosinophils, a type of immune cell.
Mepolizumab is approved as Nucala for certain diseases marked by high eosinophil counts, including a rare form of ANCA-associated vasculitis, an autoimmune condition.
MATINEE’s full data, which the company expects to present at a future scientific meeting, could shape ongoing discussions with regulators in a step toward making it a treatment option for some COPD patients.
A previous regulatory application of the therapy’s approval as an add-on to maintenance treatment to reduce COPD exacerbations, or sudden periods of symptom worsening, was rejected by the U.S. Food and Drug Administration in 2018. The agency asked for more clinical data that showed its efficacy in this patient population.
Up to 40% of patients with a diagnosis of COPD have type 2 inflammation marked by high eosinophil counts, which is linked to an increased risk of exacerbations that can result in cumulative damage to the lungs and a gradual lung function decline.
Many patients continue to have recurrent exacerbations despite standard inhaled treatment with corticosteroids or other approved medications, suggesting an approach that targets the inflammatory response mediated by eosinophils is needed. Available for injection under the skin, mepolizumab reduces the number of eosinophils by blocking IL-5, a signaling protein involved in the cells’ growth, survival, and activation.
Reduction in COPD exacerbations with mepolizumab
GSK’s mepolizumab program in COPD is made up of three placebo-controlled Phase 3 clinical trials. In the first two, METREX (NCT02105948) and METREO (NCT02105961), mepolizumab reduced the frequency of exacerbations and improved quality of life for patients with an eosinophilic profile, reflected by high eosinophil counts. Greater effects were seen in patients with higher counts of eosinophils at screening.
MATINEE was designed to supplement the clinical data. The global study recruited 806 adults, ages 40 and older, with broad clinical presentations of COPD who were receiving optimized inhaled maintenance therapy.
The participants were randomly assigned to either mepolizumab (100 mg/mL) or a placebo, delivered as an injection under the skin using a pre-filled syringe once every four weeks for up to two years. The study’s main goal was to see if adding mepolizumab to standard inhaled treatment could reduce the frequency of moderate or severe exacerbations.
Moderate exacerbations were defined as those requiring treatment with corticosteroids and/or antibiotics. Severe exacerbations were those that required hospital stays of at least 24 hours or that led to death. Their frequency was calculated as an annualized rate, a measure of the number of exacerbations adjusted to one year.
As an add-on, mepolizumab resulted in a statistically significant and clinically meaningful reduction in the annualized rate of moderate to severe exacerbations over the placebo, top-line results showed. Also, preliminary safety data in COPD patients were consistent with the known safety profile of mepolizumab for its approved indications.
About the Author
