PGx6470: Genetics of Mepolizumab (SB240563) Treatment Response in Severe Asthmatics in MEA112997

Trial description: The frequency of acute asthma exacerbations may be largely controlled by inflammation involving the eosinophil production and activation pathways, regulated by interleukin-5 (IL-5). In a recent study conducted in patients with severe asthma with SB240563 (mepolizumab; a humanized monoclonal antibody to IL-5), the frequency of asthma exacerbations was significantly less in mepolizumab-treated subjects than in placebo-treated subjects. Therefore, the pathways that determine frequent exacerbators are likely those that identify subjects best responding to mepolizumab. The overall objective of this pharmacogenetic study is to identify genetic markers that are associated with measures of response to mepolizumab in subjects with severe asthma. The primary response measure will be the rate of clinically significant asthma exacerbations per year. Secondary measures of response will include: time to first clinically significant asthma exacerbation, frequency of severe asthma exacerbation requiring emergency room visits or hospitalization, and time to first severe asthma exacerbation. Distinct marker sets will include: SNPs for which there was prior evidence for association with asthma phenotypes or eosinophilia, additional SNPs within or near candidate IL-5 eosinophil activation pathway genes, and SNPs throughout the genome that do not map to any of the candidate genes investigated. Selected HLA allele types imputed based on available genetic data will also be evaluated for association with response to mepolizumab treatment.