The success rate of late-stage clinical trials is less than 50%, even for today’s targeted therapies. Researchers are beginning to understand that genetics might play a role in why even the most promising drugs fail to deliver their hoped for efficacy.
Believing that pharmacogenomics could hold the answer, Dr. Marie-Pierre Dubé and a research team at the Montreal Heart Institute decided to use genetic tools to study dalcetrapib, a failed cholesterol drug. Designed to raise “good” HDL cholesterol, dalcetrapib had not significantly reduced cardiovascular adverse events in a Phase 3 clinical trial. Her team used the HumanOmni2.5Exome BeadChip to determine if there was a group of subjects in the trial who had benefited from dalcetrapib.
Data from the team’s genome-wide association study (GWAS) showed a strong association between the effects of dalcetrapib and a specific allele on chromosome 16. Those with the protective genotype saw a 39% reduction in cardiovascular events than placebo. A genetics-guided Phase 3 clinical study is now underway. Dr. Dubé is “inspired by the success we had with dalcetrapib and with the potential that pharmacogenomics is finally offering.”