In patients with refractory hypercholesterolemia who have high low-density lipoprotein (LDL) cholesterol levels after lipid-lowering therapies at maximum doses are at a higher risk of atherosclerosis. Evinacumab is a monoclonal antibody that could alleviate the risk of atherosclerosis in patients with refractory hypercholesterolemia. This study aims to examine the safety and efficacy of subcutaneous and intravenous evinacumab in patients with refractory hypercholesterolemia.
This placebo-controlled, double-blind, phase 2 trial included a total of 272 patients with refractory hypercholesterolemia who did or did not have heterozygous familial hypercholesterolemia. The patients were assigned to the following groups: evinacumab 450 mg/week, evinacumab 300 mg/week, evinacumab/ 2 weeks, or placebo. The primary outcome of the study was the percent change from baseline in the LDL cholesterol levels.
At week 16, the differences in the LDL cholesterol level (squares mean change) in the 450 mg/week, 300 mg/week, and 300 mg/2 weeks were –56.0, –52.9, and –38.5 percent points, respectively. The incidence of serious adverse events across all groups included in the trial varied between 3 and 16%.
The research concluded that in patients with refractory hypercholesterolemia, treatment with evinacumab was associated with a significant reduction in LDL cholesterol level compared with placebo. The lowering effect was directly proportional to the amount of the dose.