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Asthma Drug Mepolizumab Shows Promise in Phase III Studies
Positive data have been reported from two pivotal phase III studies of mepolizumab (GlaxoSmithKline), an investigational interleukin (IL)-5 antagonist monoclonal antibody, in asthma patients. The new findings were published September 8 in the New England Journal of Medicine.
The Mepolizumab as Adjunctive Therapy in Patients With Severe Asthma (MENSA) trial was a 32-week double-blind, double-dummy, placebo-controlled, parallel-group study involving 576 patients with severe asthma who had experienced frequent exacerbations despite treatment with high-dose inhaled corticosteroids (ICS) plus at least one other controller medication. All of the patients were also required to have a blood eosinophil count of 150 cells/mcL or greater at the initiation of treatment or to have had blood eosinophil counts of 300 cells/mcL or greater during the past 12 months.
The patients remained on their current asthma maintenance therapy throughout the study and were randomly assigned to receive intravenous (IV) mepolizumab 75 mg, subcutaneous (SC) mepolizumab 100 mg, or placebo every 4 weeks.
For the primary endpoint of the reduction in exacerbations (defined as worsening of asthma requiring the use of systemic corticosteroids and/or hospitalization), both mepolizumab treatment arms showed a statistically significant reduction in the frequency of clinically significant asthma exacerbations compared with placebo (75 mg IV, 47%, P < 0.001; 100 mg SC, 53%, P < 0.001).
The Steroid Reduction With Mepolizumab Study (SIRIUS) was a 24-week double-blind, placebo-controlled, parallel-group trial designed to evaluate the use of mepolizumab 100 mg SC every 4 weeks in comparison with placebo in reducing daily oral corticosteroid (OCS) use while maintaining asthma control. A total of 135 patients with severe asthma who were being treated with OCS or high-dose ICS plus an additional controller medication were enrolled. All of the patients were required to have a blood eosinophil count of 150 cells/mcL or greater at the initiation of treatment or to have had blood eosinophil counts of 300 cells/mcL or greater during the past 12 months.
Before randomization, an OCS optimization phase was conducted to ensure that the patients genuinely needed OCS to control their asthma and to establish the lowest optimal dose. The patients then started treatment (weeks 0 to 4). Between weeks 4 and 20, OCS was reduced in patients with stable disease, and this was followed by a maintenance period (weeks 20 to 24).
The trial’s primary efficacy endpoint was the percentage reduction of the daily OCS dose during weeks 20 to 24 compared with the dose determined during the optimization phase. Mepolizumab was effective in reducing OCS while maintaining control (P = 0.008).
The median overall reduction from baseline in OCS dose was 50% for patients treated with mepolizumab compared with 0% in the placebo group (P = 0.007). Patients treated with mepolizumab also reported significant improvements in their Asthma Control Questionnaire-5 scores and in their quality of life, as measured by the St. George’s Respiratory Questionnaire (SGRQ) (0.52 points [P = 0.004] and 5.8 points [P = 0.019], respectively).
Total cessation of daily OCS use (a secondary endpoint) was achieved by 14% of the patients treated with mepolizumab compared with 8% of those given placebo, which was not statistically significant (P = 0.41).
Mepolizumab is an investigational humanized immunoglobulin G1 monoclonal antibody that binds to IL-5, thereby stopping it from binding to its receptor on the surface of eosinophils. Inhibiting IL-5 binding in this way reduces blood, tissue, and sputum eosinophil levels.
Mepolizumab is being investigated as a potential treatment for a subgroup of patients with severe asthma and high eosinophil levels (defined as 50 cells/mcL or greater at screening or 300 cells/mcL or greater within 12 months before screening) who experience disease exacerbation despite treatment with OCS or high-dose ICS and an additional controller, such as a long-acting beta-2 agonist. In addition, mepolizumab is being investigated in patients with eosinophilic chronic obstructive pulmonary disease (COPD) or eosinophilic granulomatosis with polyangiitis (EGPA).
Mepolizumab is not approved anywhere in the world.
Source: GlaxoSmithKline; September 8, 2014.