Date: 2017-05-10
Type of
information: Interim results
phase: 3
Announcement: interim results
Company: GSK (UK)
Product: mepolizumab
Action
mechanism:
- monoclonal antibody. Mepolizumab is an investigational fully humanised IgG monoclonal antibody specific for interleukin 5 (IL-5) which is in development for severe refractory asthma in patients who exacerbate despite high-dose inhaled (ICS) or oral corticosteroids (OCS) and long-acting beta-2 agonist use. IL-5 is a cytokine which regulates the growth, activation and survival of eosinophils (white blood cells) and provides an essential signal for the movement of eosinophils from the bone marrow into the lung. Mepolizumab binds to human IL-5, stopping it from binding to its receptor on the surface of eosinophils. Inhibiting IL-5 binding in this manner reduces blood, tissue and sputum eosinophil levels, which in turn reduces the frequency of exacerbations.
Disease: chronic obstructive pulmonary disease (COPD) with an eosinophilic phenotype
Therapeutic
area: Inflammatory diseases - Respiratory diseases
Country: USA
Trial
details:
- The phase III programme consists of two pivotal studies (117113 and 117106). Each study uses a 52-week multi-centre, randomised, placebo controlled, double-blind, parallel group design. The primary endpoint in both is the frequency of moderate / severe exacerbations. Treatment was 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.
- Study 117113 (METREO) 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).(NCT02105961)
- Study 117106 (METREX) 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.will randomise patients to mepolizumab 100mg SC or placebo administered every four weeks. (NCT02105948)
Latest
news:
- • On May 10, 2017, GSK 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 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).
- 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.
- • On April 29, 2014, GSK has announced the start of a phase III programme to evaluate the efficacy and safety of mepolizumab as an adjunctive therapy for adults who have severe chronic obstructive pulmonary disease (COPD). The programme will enrol approximately 1500 patients who are at high risk of COPD exacerbations despite the use of standard background therapy. The phase III programme consists of two pivotal studies (117113 and 117106) that together will integrate dose-ranging and long-term efficacy and safety evaluations. Each study uses a 52-week multi-centre, randomised, placebo controlled, double-blind, parallel group design. The primary endpoint in both is the frequency of moderate / severe exacerbations. Study 117113, will randomise patients to either mepolizumab 100mg subcutaneous (SC), mepolizumab 300mg SC or placebo, administered every four weeks. All patients will be required to have a blood eosinophil count above a pre-specified threshold to be eligible for this study. Study 117106 will randomise patients to mepolizumab 100mg SC or placebo administered every four weeks. Patients in both studies will continue on baseline standard of care COPD medications throughout the entire duration of the study.
Is
general: Yes
