Identifying Predictors of Drug Efficacy in Clinical Development Using Genome-Wide Association Approach

• Activity Number: 359
• Type: Topic Contributed
• Date/Time: Tuesday, August 4, 2009 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Gbenga R. Kazeem*+ and Silviu Bacanu and Nelson R. Matthew and Magaret Ehm and Wang Sue-Jane
• Companies: GlaxoSmithKline and GlaxoSmithKline and GlaxoSmithKline and GlaxoSmithKline and FDA
• Keywords: Genome-wide association ; Biomarkers ; Drug efficacy ; Clinical studies ; Genetic markers

Abstract

Several recent successes in genome-wide association (GWA) studies have provided some insights into the genetic architecture that underlies many complex human traits. However, using the GWA approach to identify genetic biomarkers that influence drug efficacy, and that could improve clinical development, remains largely untested. In a scientific collaboration between the FDA and GSK on the development of a potential genetic composite biomarker, blinded whole-genome data sets, obtained from three phase IIb and III clinical trials, were analyzed under a variety of statistical models. Data include a quantitative baseline and response variables and 500,000 marker genotypes from 961 subjects. Strategies employed to analyze these data sets will be described. These results will help to determine how genetic variants that influence drug efficacy can be identified and incorporated into classifiers.