Dalcetrapib
Review highlights ADCY9 pharmacogenomics as a model for rescuing dalcetrapib and future lipid trials (Curr Opin Lipidol 2016)
Original title: Pharmacogenomic approaches to lipid-regulating trials
This review examines pharmacogenomics as a strategy to address the high cost, long duration, and frequently neutral results of cardiovascular outcome trials, which have hindered drug development despite the residual cardiovascular risk that remains after statin therapy. As its central example, the authors highlight that variants in the ADCY9 gene were significantly associated with responses to dalcetrapib across clinical outcomes, atherosclerosis imaging, cholesterol efflux, and inflammation, evidence that supported launching a new prospective trial in a genetically defined population. The authors conclude that pharmacogenomics holds substantial potential to reduce failure rates in lipid drug development and to identify patients most likely to benefit.
Original abstract
Purpose Of Review: Randomized clinical outcome trials are costly, long, and often yield neutral or modestly positive results, and these issues have impeded cardiovascular drug development in the past decade. Despite the significant reduction of cardiovascular morbidity and mortality with statins, substantial residual risk of major cardiovascular events remains. This could be because of the difficulty of demonstrating benefits of new drugs in addition to the current standard of care in unselected populations as well as the interindividual variability in drug response. Pharmacogenomics is a promising avenue for the development of novel or failed drugs and for the repurposing of other medications.
Recent Findings: Several variants were identified in genes that were associated with the effects of statins on plasma lipids. Genomic studies of mutations in genes that encode drug targets have the potential to inform on the link between drug therapy acting on those targets and clinical outcomes. Recently, ADCY9 gene variants were shown to be significantly associated with responses to dalcetrapib in terms of clinical outcomes, atherosclerosis imaging, cholesterol efflux, and inflammation, which provided support for the conduct of a new prospective clinical trial in a genetically determined population.
Summary: Pharmacogenomics hold great potential in future lipid trials to decrease failure rates in drug development and to identify patients who will respond with greater benefits and smaller risk.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.