Evinacumab to treat hypercholesterolemia

Abstract

Cardiovascular disease is the most common cause of death worldwide and is mainly due to atherosclerosis. Elevated levels of low-density lipoprotein cholesterol (LDL-C) are the main risk factor for atherosclerosis. Treatment with existing therapies for dyslipidemia and life-style changes are often sufficient to reach the lipid targets and decrease the cardiovascular risk of patients. However, there are patients who cannot reach their targets. Especially patients with genetically caused dyslipidemias, such as familial hypercholesterolemia, often are not able to reach the targets, leading to an increased cardiovascular risk and higher mortality. Evinacumab is a human monoclonal antibody which binds and inhibits angiopoietin-like protein 3 (ANGPTL3). The inhibition of ANGPTL3 leads to increased activity of the lipoprotein lipase (LPL) and the endothelial lipase (EL). LPL is the main enzyme for hydrolyzation of triglyceride-rich lipoproteins. EL is a phospholipase which preferentially hydrolyzes high-density lipoprotein (HDL) but also decreases circulating LDL-C. The increased LPL and EL activity reduces circulating levels of very-low-density lipoprotein cholesterol, triglycerides, LDL-C and HDL-cholesterol. Evinacumab leads to a significant decrease in circulating lipids and attainment of lipid targets in these patients. Further studies with evinacumab to assess its lipid-decreasing potential and to evaluate its impact on cardiovascular risk and mortality are eagerly awaited.

Keywords: Anti-angiopoietin-like protein 3 (ANGPTL3) agents; Evinacumab; Hypercholesterolemia; Lipid-lowering therapy; Metabolic diseases; Monoclonal antibodies; Treatment of lipoprotein disorders.