Lessons learned from the evinacumab trials in the treatment of homozygous familial hypercholesterolemia

Homozygous familial hypercholesterolemia (HoFH) is a life-threatening disease characterized by extremely elevated LDL cholesterol (LDL-C) levels which result in premature atherosclerotic cardiovascular disease. As conventional lipid-lowering therapies, which mainly depend on LDL receptors for LDL particle clearance, remain insufficient for reaching the recommended LDL-C levels in HoFH, agents acting independently of LDL receptors, such as ANGPTL3 inhibitors, constitute a promising target. Evinacumab, a monoclonal antibody directed against ANGPTL3, was approved in the USA in 2021 for treating patients with HoFH. Evinacumab has shown an adequate safety profile with strong LDL-lowering efficacy. This review highlights the development path of evinacumab and provides insight on the lessons learned from trials as well as the hurdles facing accessibility.