Mepolizumab is an investigative treatment for adults with eosinophilic chronic obstructive pulmonary disease (COPD) being developed by GSK.

How mepolizumab works

Mepolizumab works by depleting eosinophils, a type of white blood cell, the production, activation, recruitment, and proliferation at inflammation sites of which is controlled by a molecule called interleukin 5 (IL5). In excess, eosinophils can cause inflammation in the lungs, ultimately leading to excess sputum production leading to the worsening of respiratory symptoms in COPD patients.

Mepolizumab is an antibody against IL5 that has demonstrated efficacy in people with severe asthma. It is designed to weaken the immune response in the airways by reducing the number of eosinophils. About 18 percent of COPD patients have high levels of eosinophils in their airways, and treatment for these patients has been tested in Phase 3 clinical trials.

Mepolizumab was approved by the U.S. Food & Drug Administration (FDA) in 2015 under the brand name Nucala, as an add-on maintenance treatment for severe asthma patients with an eosinophilic phenotype. 

Mepolizumab in clinical trials for COPD

Three Phase 3 clinical trials tested mepolizumab as a treatment for COPD.

The first study (NCT01463644), which ended in 2015, evaluated mepolizumab’s effects in COPD patients with airway inflammation not caused by asthma. In this double-blind study, 18 participants (ages 40–80) received infusions of mepolizumab (750 mg) or placebo once a month for six months in addition to their inhaled medications and were monitored every month or at the time of an exacerbation. The primary measure of the study was the percentage decrease in sputum eosinophils. The secondary measure was the proportion of patients with a major exacerbation. Results showed that mepolizumab reduced sputum and blood eosinophils, but did not improve the secondary measures of lung function and exacerbation rates. 

The other two Phase 3 trials (NCT02105948 and NCT02105961) compared mepolizumab (at 100 mg and 100 or 300 mg respectively) with placebo, both taken as an injection under the skin every four weeks for 52 weeks. Both trials included patients with COPD who had moderate or severe exacerbations while taking triple inhaled therapy as a maintenance treatment.

The first trial included 837 people with severe COPD exacerbations at 117 sites in 16 different countries, and the second included 674 patients at 168 sites in 15 countries who had a baseline blood eosinophil count of at least 150 cells/microliters. Patients were evaluated for the frequency of disease flares — moderate or severe — and other exacerbation measures. 

Both trials ended in early 2017 and the results were jointly published in September 2017 in The New England Journal of Medicine. They showed that patients who were treated with 100 mg of mepolizumab had a significantly lower rate of moderate to severe exacerbations compared to patients who were given a placebo. Investigators found no evidence that higher doses of mepolizumab had a greater effect.

One trial found that the time to the first moderate or severe exacerbation was significantly longer in patients treated with mepolizumab compared to those treated with placebo, but the other did not.

Both trials found that there were no differences between mepolizumab and placebo in terms of exacerbations leading to an emergency department visit or hospitalization, impact on daily life and well-being of patients (measured by the St. George’s Respiratory Questionnaire – SGRQ), and impact of COPD on patients’ life (measured by the COPD Assessment Test – CAT). They also found that mepolizumab had greater effects on the rate of moderate to severe exacerbations in patients with a higher blood eosinophil count. Investigators, therefore, proposed that blood eosinophil counts might be a potential biomarker to be used in the management of COPD. 

Other details

The most frequent reported side effects of mepolizumab use include injection site reaction (pain, redness, swelling or itching), headache, back pain, and fatigue.

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