Bempedoic acid: mechanism of action

Bempedoic acid (ETC-1002) is an oral, once-daily, small molecule with a half-life of 15-24 h. It is responsible for the inhibition of ATP citrate lyase (ACLY), a cytosolic enzyme upstream of HMG-CoA reductase. Bempedoic acid is a prodrug rapidly converted in the liver to a coenzyme A derivate, ETC-1200-CoA, by an endogenous liver very long-chain acyl-CoA synthetase-1 (ACSVL1). Since ACSVL1 is not present in the skeletal muscle, less risk of myalgia symptoms and myopathy is expected. In a Mendelian randomization study, combined exposure to variants in the ACLY, HMGCR and Niemann-Pick C1-Like 1 genes produced an additive decrease in low-density lipoprotein cholesterol levels and additive reduction in the risk of cardiovascular events. The aim of this review is to describe bempedoic acid mechanism of action, and its pharmacokinetic and pharmacodynamic characteristics.