Evinacumab in Patients with Refractory Hypercholesterolemia

BACKGROUND: Patients suffering from refractory hypercholesterolemia, characterized by persistently high low-density lipoprotein (LDL) cholesterol levels despite receiving lipid-lowering therapies at maximum tolerated doses, face an elevated risk of atherosclerosis. The efficacy and safety of both subcutaneous and intravenous formulations of evinacumab, a fully human monoclonal antibody targeting angiopoietin-like 3, have not been established in this patient population. METHODS: We conducted a double-blind, placebo-controlled, phase 2 trial. We enrolled patients with or without heterozygous familial hypercholesterolemia who had refractory hypercholesterolemia. Eligibility required a screening LDL cholesterol level of 70 mg per deciliter or higher if atherosclerosis was present, or 100 mg per deciliter or higher if atherosclerosis was absent. Patients were randomly assigned to receive either subcutaneous evinacumab, intravenous evinacumab, or placebo. The primary endpoint was the percentage change from baseline in the LDL cholesterol level at week 16.

RESULTS: A total of 272 patients were enrolled in the study. At week 16, the mean (±SE) percentage change from baseline in the LDL cholesterol level was –50.5±3.7% in the subcutaneous-evinacumab group, –49.0±3.9% in the intravenous-evinacumab group, and +1.9±3.7% in the placebo group. The most frequently reported adverse events included nasopharyngitis, headache, and influenza. No new safety concerns were identified in relation to the treatment groups throughout the study period.

CONCLUSIONS: Evinacumab, when administered either subcutaneously or intravenously, significantly reduced LDL cholesterol levels in patients with refractory hypercholesterolemia. Furthermore, no new safety concerns were identified with its use.

BACKGROUND: Patients suffering from refractory hypercholesterolemia, characterized by persistently high low-density lipoprotein (LDL) cholesterol levels despite receiving lipid-lowering therapies at maximum tolerated doses, face an elevated risk of atherosclerosis. The efficacy and safety of both subcutaneous and intravenous formulations of evinacumab, a fully human monoclonal antibody targeting angiopoietin-like 3, have not been established in this patient population. METHODS: We conducted a double-blind, placebo-controlled, phase 2 trial. We enrolled patients with or without heterozygous familial hypercholesterolemia who had refractory hypercholesterolemia. Eligibility required a screening LDL cholesterol level of 70 mg per deciliter or higher if atherosclerosis was present, or 100 mg per deciliter or higher if atherosclerosis was absent. Patients were randomly assigned to receive either subcutaneous evinacumab, intravenous evinacumab, or placebo. The primary endpoint was the percentage change from baseline in the LDL cholesterol level at week 16.

RESULTS: A total of 272 patients were enrolled in the study. At week 16, the mean (±SE) percentage change from baseline in the LDL cholesterol level was –50.5±3.7% in the subcutaneous-evinacumab group, –49.0±3.9% in the intravenous-evinacumab group, and +1.9±3.7% in the placebo group. The most frequently reported adverse events included nasopharyngitis, headache, and influenza. No new safety concerns were identified in relation to the treatment groups throughout the study period.

CONCLUSIONS: Evinacumab, when administered either subcutaneously or intravenously, significantly reduced LDL cholesterol levels in patients with refractory hypercholesterolemia. Furthermore, no new safety concerns were identified with its use.