GlaxoSmithKline has announced preliminary results of two pivotal Phase III studies evaluating the efficacy and safety of mepolizumab, an IL-5 antagonist monoclonal antibody, as an investigational add on treatment for adults who have chronic obstructive pulmonary disease (COPD) with an eosinophilic phenotype.
GlaxoSmithKline has announced preliminary results of two pivotal Phase III studies evaluating the efficacy and safety of mepolizumab, an IL-5 antagonist monoclonal antibody, as an investigational add on treatment for adults who have chronic obstructive pulmonary disease (COPD) with an eosinophilic phenotype.
The primary objective of the 52-week treatment studies was to investigate whether reducing eosinophils (a type of white blood cell) with subcutaneous mepolizumab 100mg and 300mg would decrease the frequency of moderate and severe exacerbations in COPD patients at high risk of exacerbations despite use of optimal standard of care therapy.
- Study 117106 (METREX) randomised 836 patients to mepolizumab 100mg or placebo across two groups according to blood eosinophil count. In the group with higher eosinophils, there was a statistically significant reduction in the frequency of moderate and severe exacerbations for mepolizumab 100mg compared to placebo (18%, p=0.036 after multiplicity adjustment).
- Study 117113 (METREO) randomised 674 patients to mepolizumab 100mg, mepolizumab 300mg or placebo. A reduction in the frequency of moderate and severe exacerbations for mepolizumab compared to placebo was seen which was not statistically significant (20% for 100mg, p=0.068; 14% for 300mg, p=0.140 after multiplicity adjustment).
Steve Yancey, Vice President and Medicine Development Lead for mepolizumab, GSK said: “We embarked on these two studies in our pursuit to help COPD patients with an eosinophilic phenotype who still exacerbate despite optimal use of medicines available today. 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. We will review the full data when available to determine our next steps.”
Full results will be submitted for presentation at an upcoming scientific congress and for publication in a peer-reviewed journal.
No safety concerns were identified on review of headline data from these studies. The proportion of patients experiencing adverse events and serious adverse events while receiving treatment was 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 100mg group and the frequency of serious adverse events was 28% in the placebo group and 25% in the mepolizumab 100mg group. In the METREO study, the frequency of adverse events was 81% in the placebo group, 83% in the mepolizumab 100mg group and 85% in the mepolizumab 300mg group and the frequency of serious adverse events was 26% in the placebo group, 23% in the mepolizumab 100mg group and 24% in the mepolizumab 300mg group.
Study design
The Phase III studies were multi-centre, randomised, placebo controlled, double blind, parallel group design with treatment administered by subcutaneous (SC) injection every four weeks in COPD patients at high risk of exacerbations despite the use of optimal standard of care background therapy which employed inhaled triple therapy consisting of an inhaled corticosteroid (ICS), long-acting beta agonist (LABA) and long-acting muscarinic antagonist (LAMA). The total duration of the studies was approximately 62 weeks consisting of a 1-2 week screening period, 52-week treatment period and 8-week follow-up period.
The METREX study (117106) evaluated mepolizumab 100mg or placebo across a range of baseline blood eosinophil counts. Patients were stratified according to i) blood eosinophil count of >150 cells/µl at study entry or >300 cells/µl within the past year (higher eosinophil group) or ii) blood eosinophil count of <150 cells/µl at study entry and no evidence of >300 cells/µl within the past year.
The METREO study (117113) evaluated mepolizumab 100mg, mepolizumab 300mg or placebo in patients with a blood eosinophil count of >150 cells/µl at study entry or >300 cells/µl within the past year (higher eosinophil group).
Moderate exacerbations were defined as those requiring treatment with systemic corticosteroids and/or antibiotics. Severe exacerbations were those requiring hospitalisation or resulted in death.
