Two pivotal phase III studies yielded mixed results for mepolizumab (Nucala) as an add-on treatment for patients with eosinophilic phenotype chronic obstructive pulmonary disease (COPD), according to (GSK).
The trials were designed to examine whether adding the biologic therapy to optimal standard-of-care treatment would decrease the frequency of moderate to severe exacerbations in this high-risk COPD group. The drug, an interleukin-5 inhibitor, is currently approved as add-on therapy for severe asthma.
In the METREX study, 836 patients with a range of eosinophil counts were randomized to 100-mg mepolizumab or placebo. A statistically significant reduction in the frequency of exacerbations was seen in mepolizumab-treated patients with higher eosinophil counts versus placebo (18% reduction, P=0.036).
In the METREO study, 674 patients with blood eosinophil counts >150 cells/μl at study entry, or >300 cells/μl within the past year, were randomized to mepolizumab at either 100 mg or 300 mg doses, or placebo. Patients had adjusted reductions in the frequency of exacerbations at both doses of the biologic versus placebo (20% for 100 mg and 14% for 300 mg), but these failed to reach statistical significance.
In a statement, Steve Yancey, GSK vice president, said the company would review the full data when it is available to "determine our next steps."
"We embarked on these two studies in our pursuit to help COPD patients with an eosinophilic phenotype who still exacerbate despite optimal use of medications available today," Yancey said. "We believe the reduction in moderate and severe exacerbations observed are of clinical relevance given the need for a new treatment approach in these difficult to treat patients."
COPD specialist James Donohue, MD, of the University of North Carolina School of Medicine in Chapel Hill, said the reduction in exacerbations with the add-on therapy was encouraging, but he added that the failure to reach statistical significance in the METREO study was puzzling.
"The effect sizes look terrific. A 20% and 14% reduction in exacerbations with an add-on treatment is very impressive -- almost unheard of -- in COPD, but the devil is in the details," noted Donohue, who was not involved in the study, to ľֱ.
Mepolizumab is a first-in-class anti-IL-5 biologic that was initially developed to treat patients with severe eosinophilic-phenotype asthma. The drug acts by binding to the signalling protein IL-5 to prevent it from binding to its receptor on the surface of eosinophils.
Donohue said that because the FDA generally requires that parallel studies both meet their statistical endpoints, GSK may be required to do additional studies if the company pursues a COPD indication for mepolizumab.
"I hope the company does follow through," he said. "IL-5 agents are used for TH2 inflammation, which is very important in asthma. It is less important in COPD, except for certain populations such as asthma/COPD overlap or patients with high eosinophils in the blood. These patients respond well to these agents."
The headline data from the two trials identified no new safety concerns, with the proportion of patients experiencing adverse events and serious adverse events while on treatment being similar for mepolizumab and placebo.
In the METREX study, the frequency of adverse events was 81% in the placebo group and 79% in the mepolizumab 100-mg group and the frequency of serious adverse events was 28% in the placebo group and 25% in the mepolizumab 100-mg group.
In the METREO study, the frequency of adverse events was 81% in the placebo group, 83% in the mepolizumab 100-mg group and 85% in the mepolizumab 300-mg group, and the frequency of serious adverse events was 26%, 23%, and 24%, respectively, in the three groups.