Will evinacumab become the standard treatment for homozygous familial hypercholesterolemia?

Introduction: Homozygous Familial Hypercholesterolemia (HoFH) is a very severe genetic form of hypercholesterolemia. Lacking LDL receptors in the liver, subjects with HoFH have raised plasma levels of LDL cholesterol, and up to 100 times higher risk of premature atherosclerotic cardiovascular disease than the general population.Areas covered: This evaluation is of a phase 3 trial of evinacumab; Evinacumab Lipid Studies in Patients with Homozygous Familial Hypercholesterolemia (ELIPSE HoFH). Evinacumab is a human monoclonal antibody inhibitor of angiopoietin-like protein 3 (ANGPTL3). In ELIPSE HoFH, evinacumab reduced LDL cholesterol by 47.1 ± 4.6%, HDL cholesterol by 30.4%, and triglycerides by 50.4 ± 7.7%.Expert opinion: Evinacumab is not the ideal treatment for HoFH as it does not reduce LDL cholesterol levels to treatment targets while increasing HDL cholesterol. Although the incidence of adverse effects with evinacumab was low in ELIPSE HoFH, further studies are necessary to clarify its effects on liver enzymes and clinical cardiovascular outcomes. Evinacumab is a candidate to become the standard treatment for HoFH, as it may be better tolerated and/or more efficacious than the presently available specific treatment (lomitapide). However, the widespread use of evinacumab to treat high triglycerides or LDL cholesterol is unlikely due to evinacumab decreasing HDL cholesterol.