GlaxoSmithKline plc (GSK) has initiated phase III programme to evaluate the efficacy and safety of mepolizumab, an investigational IL-5 antagonist, as adjunctive therapy in severe uncontrolled refractory asthma.

The phase III programme includes two key studies:

MEA115588: A 32-week multi-centre, randomised, double-blind, double-dummy, placebo-controlled study in patients with severe uncontrolled refractory asthma. The primary endpoint of the study is to evaluate the efficacy of mepolizumab 75 mg intravenous (i.v.) and 100 mg subcutaneous (SC) every four weeks versus placebo on the frequency of clinically significant exacerbations in patients with severe refractory asthma.

MEA115575: A 24-week randomised, double-blind, placebo-controlled, parallel-group, multi-centre study to evaluate the use of mepolizumab 100mg subcutaneous adjunctive therapy every four weeks to reduce steroid use in patients with severe refractory asthma.

The phase III programme also includes safety extension trials that will further assess treatment of subsequent asthma attacks in mepolizumab-naive as well as previously-treated patients.

“The progression of this phase III programme represents a significant milestone in the clinical development of mepolizumab as a potential treatment option for patients with severe uncontrolled refractory asthma,” said Steve Yancey, vice-president and Head of the mepolizumab development team.

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. Mepolizumab is not approved for use anywhere in the world.