Bypassing the LDL Receptor in Familial Hypercholesterolemia

This editorial discusses the promise of evinacumab, a monoclonal antibody against angiopoietin-like 3 (ANGPTL3), in treating homozygous familial hypercholesterolemia (HoFH) a condition defined by severely elevated LDL cholesterol due to dysfunctional LDL receptors. Conventional lipid-lowering agents like statins and PCSK9 inhibitors depend on LDL receptor activity, rendering them less effective in HoFH patients. Evinacumab offers a receptor-independent mechanism: by inactivating ANGPTL3, it reduces plasma LDL and triglyceride levels, potentially diminishing cardiovascular risk. The editorial reviews findings from a phase 3 trial showing nearly 50% reduction in LDL cholesterol among evinacumab-treated patients versus placebo. The article also explores broader implications, including utility in patients with refractory hypercholesterolemia or familial chylomicronemia syndrome. The author concludes that ANGPTL3 targeting represents a major advance, potentially widening treatment options beyond current modalities.

This editorial discusses the promise of evinacumab, a monoclonal antibody against angiopoietin-like 3 (ANGPTL3), in treating homozygous familial hypercholesterolemia (HoFH) a condition defined by severely elevated LDL cholesterol due to dysfunctional LDL receptors. Conventional lipid-lowering agents like statins and PCSK9 inhibitors depend on LDL receptor activity, rendering them less effective in HoFH patients. Evinacumab offers a receptor-independent mechanism: by inactivating ANGPTL3, it reduces plasma LDL and triglyceride levels, potentially diminishing cardiovascular risk. The editorial reviews findings from a phase 3 trial showing nearly 50% reduction in LDL cholesterol among evinacumab-treated patients versus placebo. The article also explores broader implications, including utility in patients with refractory hypercholesterolemia or familial chylomicronemia syndrome. The author concludes that ANGPTL3 targeting represents a major advance, potentially widening treatment options beyond current modalities.