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Life sciences · Journal article
American Journal of Preventive Cardiology · August 11, 2026
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Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder that results in severely elevated low-density lipoprotein cholesterol (LDL-C) due to dysfunctional activity of the low-density lipoprotein receptor (LDLR) and impaired clearance of LDL-C. Individuals with HoFH require intensive lipid-lowering therapies (LLTs), ideally starting in early childhood, to aggressively lower LDL-C levels and mitigate risk of early-onset atherosclerotic cardiovascular disease caused by lifetime exposure to high LDL-C levels. However, most conventional LLTs lower LDL-C through an LDLR-dependent mechanism, limiting their effectiveness in individuals with HoFH, who have little to no LDLR activity. Evinacumab is a fully human monoclonal antibody against angiopoietin-like protein 3 (ANGPTL3), and has an LDLR-independent mechanism of action. By inhibiting ANGPTL3, evinacumab increases the activity of lipoprotein lipase and endothelial lipase, consequently increasing the clearance of LDL precursors and lowering LDL-C levels. Following its initial US Food and Drug Administration approval in 2021, evinacumab has been approved to treat individuals with HoFH from 1 year of age in the US and as young as 6 months of age in multiple other countries. Here, we describe the role of evinacumab in the HoFH treatment landscape, summarize the available clinical evidence for evinacumab, and provide practical guidance on its use from the clinician's perspective.