Introduction: Familial hypercholesterolemia (FH) is characterized by lifelong 
elevation of low-density lipoprotein cholesterol (LDL-C), early onset coronary 
atherosclerosis, and premature death. FH is underdiagnosed and undertreated, but 
requires aggressive LDL-C-lowering to prevent complications. Current treatment 
strategies such as lifestyle modification and numerous LDL-C-lowering 
medications are often insufficient to achieve lipid goals in FH.Areas covered: 
Angiopoietin-like 3 protein (ANGPTL3) is intricately involved in lipid 
metabolism. Loss-of-function mutations in ANGPTL3 are associated with 
panhypolipidemia and reduced coronary atherosclerosis. Evinacumab, a fully human 
monoclonal antibody, inhibits ANGPTL3 and reduces multiple lipoprotein fractions 
~50%, including LDL-C. The use of evinacumab within the FH population is 
described as well as its regulatory journey to an approved therapeutic.Expert 
opinion: Evinacumab, with its capacity to lower multiple lipoprotein fractions, 
particularly LDL-C, independently of LDLR function has potential to 
revolutionize treatment for FH patients. Current FDA-approval is only for 
homozygous FH (HoFH), arguably the most impactful indication, but use in other 
lipid disorders is under investigation. The short-term tolerability of 
evinacumab is very good, with infrequent, mild, and transient adverse events; 
however, long-term safety data are needed. The high cost and requirement for 
intravenous administration may limit adoption of evinacumab, but dramatic 
LDL-C-lowering and need for new therapeutic options for HoFH will drive 
interest.