Evinacumab is a fully human monoclonal IgG4 antibody approved as an adjunct therapy for the treatment of homozygous familial hypercholesterolemia (HoFH) and severe forms of hypercholesterolemia. It represents a first-in-class therapeutic with a novel, non-statin mechanism. Evinacumab functions as a potent and selective inhibitor of angiopoietin-like protein 3 (ANGPTL3). By binding to and neutralizing ANGPTL3 in the bloodstream, evinacumab prevents ANGPTL3 from inhibiting two key enzymes involved in lipid metabolism: lipoprotein lipase (LPL) and endothelial lipase (EL). This inhibition leads to a dramatic reduction in all major atherogenic lipid fractions—low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides—through a mechanism that is independent of the LDL receptor pathway.