Evinacumab for Homozygous Familial Hypercholesterolemia

Background: Homozygous familial hypercholesterolemia (HoFH) is a genetic disorder causing extremely elevated LDL cholesterol levels, often unresponsive to conventional therapies. Loss-of-function variants in ANGPTL3 correlate with lower lipid levels and reduced cardiovascular risk.

Methods: In a randomized, double-blind, placebo-controlled phase 3 trial (ELIPSE HoFH), 65 patients with HoFH on stable lipid-lowering therapy received intravenous evinacumab (15 mg/kg) or placebo every four weeks over 24 weeks. The primary endpoint was percent change in LDL cholesterol at week 24.

Results: Patients receiving evinacumab showed a 47.1% mean reduction in LDL cholesterol versus a 1.9% increase in the placebo group (mean difference: -49.0 percentage points; P<0.001). The effect was consistent regardless of LDL-receptor activity. Adverse event rates were similar between groups.

Conclusions: Evinacumab significantly reduced LDL cholesterol in patients with HoFH, including those with null-null LDL-receptor variants, suggesting ANGPTL3 inhibition as a promising LDL-receptor independent strategy.

Background: Homozygous familial hypercholesterolemia (HoFH) is a genetic disorder causing extremely elevated LDL cholesterol levels, often unresponsive to conventional therapies. Loss-of-function variants in ANGPTL3 correlate with lower lipid levels and reduced cardiovascular risk.

Methods: In a randomized, double-blind, placebo-controlled phase 3 trial (ELIPSE HoFH), 65 patients with HoFH on stable lipid-lowering therapy received intravenous evinacumab (15 mg/kg) or placebo every four weeks over 24 weeks. The primary endpoint was percent change in LDL cholesterol at week 24.

Results: Patients receiving evinacumab showed a 47.1% mean reduction in LDL cholesterol versus a 1.9% increase in the placebo group (mean difference: -49.0 percentage points; P<0.001). The effect was consistent regardless of LDL-receptor activity. Adverse event rates were similar between groups.

Conclusions: Evinacumab significantly reduced LDL cholesterol in patients with HoFH, including those with null-null LDL-receptor variants, suggesting ANGPTL3 inhibition as a promising LDL-receptor independent strategy.