Mechanism of Action
Our data shows apabetalone (RVX-208) to be an inhibitor of the Bromodomain and Extraterminal Domain (“BET”) proteins. Apabetalone acts on BET proteins, including BRD4, a member of the BET-protein family. BET proteins are key players in 'epigenetics', a critical mechanism for regulating the expression of genes. Epigenetic processes are mediated by proteins, including the BET-proteins that act in concert with the DNA to make it transcriptionally active or dormant. This epigenetic control of gene expression plays a key role in the development and progression of many human diseases.
Apabetalone mediated inhibition affects multiple processes important for CVD. In addition to effects on lipoproteins, apabetalone represses pathways underlying the pathogenesis of atherosclerosis and acute coronary events, including inflammation, complement, coagulation (thrombosis) and atherogenesis. Based on mechanistic data, we believe that apabetalone treatment, or select BET inhibition, attenuates the inflammatory process that contributes to disease initiation and progression. Furthermore, we hypothesize that apabetalone treatment restores basal activity of the inflammatory and innate immune response and clotting cascade with immediate benefits to atherosclerosis and cardiovascular disease. This is consistent with observed reductions in MACE, especially in patients with an acute inflammatory component in CVD.