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.
Keywords: ANGPTL3 inhibition; cardiovascular disease; clinical trials; evinacumab; homozygous familial hypercholesterolemia; rare lipid disorders; safety and efficacy.
Homozygous familial hypercholesterolemia (HoFH) is a life-threatening rare genetic disorder characterized by extremely elevated ‘bad’ cholesterol and resulting in heart disease at a young age. As the current treatments that tend to lower the levels of ‘bad’ cholesterol remain insufficient for treating patients with this disease, emerging agents, such as inhibitors of the protein ANGPTL3, follow different biological pathways than the ones targeted by the traditional therapies and constitute a promising target for HoFH. Evinacumab, which is highly selective for ANGPTL3 inhibition, was approved in the USA in 2021 for treating patients with HoFH. Evinacumab has been shown to be safe and well tolerated, with a strong effect on decreasing ‘bad’ cholesterol levels. This review highlights the development path of evinacumab and provides insight into the lessons learned from trials as well as the hurdles facing accessibility.