A team of researchers at GSK recently presented the results from two-PHASE III Clinical Trials of Mepolizumab, a new humanized IL-5 antagonist monoclonal antibody, for the treatment of severe eosinophilic asthma at the European Respiratory Society (ERS) Congress, and is now published in the current issue of the New England Journal of Medicine (NEJM). The two studies are:
MENSA – MEpolizumab as adjunctive therapy iN patients with Severe Asthma
SIRIUS – The SteroId ReductIon with MepolizUmab Study
Mepolizumab’s mode of action consists of binding to interleukin-5 (IL-5) (a member of the group of cytokines, which are signaling molecules secreted by cells of the immune system), thereby blocking the binding of IL-5 to its receptor at the surface of eosinophils (a member of the white blood cells’ family, an important component of the immune system). IL-5 expression is especially high in eosinophils being not only the main promoter of eosinophil growth, activation, and survival, but also a key signal for eosinophil’s movement towards lungs.
Asthma is a common chronic inflammatory disease of the airways, estimated to affect 235 million people worldwide by the World Health Organization (WHO). An increased accumulation of eosinophils is now a known cause of asthma symptoms, and eosinophils correlate with severity and frequency of exacerbations.
The aim of MENSA and SIRIUS studies was to evaluate the impact of mepolizumab on a number of key endpoints in asthma disease. In both studies, the key endpoints were obtained successfully. In MENSA, patients receiving mepolizumab exhibited a significant reduction in the frequency of clinically significant asthma exacerbations compared to placebo. In SIRIUS, the daily dose of oral corticosteroid (OCS), a current treatment for asthma exacerbations, was significantly reduced during weeks 20-24 when compared with the pre-determined dose during the optimization phase. Moreover, patients within these studies experienced an improved control of asthma thereby having a higher quality of life. At present, Mepolizumab is not approved anywhere in the world.
These findings are particularly important since, despite using inhaled therapies, still 10% of asthma patients who live with severe asthma are unable to control their symptoms with inhaled therapies, and require additional anti-inflammatory medicines on a regular basis, like the use of regular doses of systemic corticosteroids.
As Steve Yancey, Medicine Development Leader of mepolizumab at GSK noted, “The relationship between over-expression of IL-5 and severe asthma has long been established, but it is only now that we have medicines that can target IL-5 as a possible way to manage eosinophilic inflammation. The combined results of these studies, taken with earlier results, confirm our belief that patients with severe eosinophilic asthma could benefit from mepolizumab. We are pleased to be sharing our findings with the scientific community to expand understanding of innovative approaches to treating eosinophilic asthma for the benefit of patients.”
GSK is aiming for global filings of mepolizumab to treat severe eosinophilic asthma by the end of 2014.
MENSA was a 32-week double-blind, double-dummy, placebo-controlled, parallel group multicentre study performed with 576 patients with severe asthma, who had a history of frequent exacerbations despite treatment with high-dose inhaled corticosteroids (ICS), with at least one other controller medication.
Patients in the study maintained their current asthma therapy throughout the study and were randomized to receive either mepolizumab 75mg intravenous (IV), 100mg subcutaneous (SC), or placebo every four weeks.
SIRIUS was a 24-week double-blind, double-dummy, placebo-controlled, parallel group multicentre study performed with 135 patients with severe asthma, who were being treated with OCS, high-dose ICS plus an additional controller medication. The study aimed to evaluate the reduction in daily oral corticosteroid (OCS) use, while maintaining asthma control with mepolizumab 100mg SC, every 4 weeks in comparison to placebo.
The study and further details for the study “Oral Glucocorticoid-Sparing Effect of Mepolizumab in Eosinophilic Asthma” was recently published in the New England Journal of Medicine.