Delhi: Evinacumab significantly lowers LDL cholesterol levels in patients with homozygous familial hypercholesterolemia receiving maximum doses of lipid-lowering therapy, according to a recent study in the New England Journal of Medicine.
Homozygous familial hypercholesterolemia patients have markedly elevated levels of low-density lipoprotein (LDL) cholesterol causing premature cardiovascular disease. This disorder is associated with genetic variants resulting in either impaired (non-null) or virtually absent (null–null) LDL-receptor activity. Loss-of-function variants in the gene encoding angiopoietin-like 3 (ANGPTL3) are associated with hypolipidemia and protection against atherosclerotic cardiovascular disease.
Evinacumab is a monoclonal antibody against ANGPTL3 that has shown potential benefits in patients with homozygous familial hypercholesterolemia. It is PCSK9 inhibitor that acts by inhibiting PCSK9 protein.
Frederick J. Raal, University of the Witwatersrand, Johannesburg, and colleagues conducted a double-blind, placebo-controlled, phase 3 trial. In the trial, 65 patients with homozygous familial hypercholesterolemia patients who were receiving stable lipid-lowering therapy, were randomly assigned in the ratio 2:1 to receive an intravenous infusion of evinacumab (at a dose of 15 mg per kilogram of body weight) every 4 weeks or placebo.
The primary outcome was the percent change from baseline in the LDL cholesterol level at week 24.
Key findings of the study include:
The mean baseline LDL cholesterol level in the two groups was 255.1 mg per deciliter, despite the receipt of maximum doses of background lipid-lowering therapy.
At week 24, patients in the evinacumab group had a relative reduction from baseline in the LDL cholesterol level of 47.1%, as compared with an increase of 1.9% in the placebo group, for a between-group least-squares mean difference of –49.0 percentage points; the between-group least-squares mean absolute difference in the LDL cholesterol level was –132.1 mg per deciliter.
The LDL cholesterol level was lower in the evinacumab group than in the placebo group in patients with null–null variants (–43.4% vs. +16.2%) and in those with non-null variants (–49.1% vs. –3.8%).
Adverse events were similar in the two groups.
"In patients with homozygous familial hypercholesterolemia receiving maximum doses of lipid-lowering therapy, the reduction from baseline in the LDL cholesterol level in the evinacumab group, as compared with the small increase in the placebo group, resulted in a between-group difference of 49.0 percentage points at 24 week," concluded the authors.
The study, "Evinacumab for Homozygous Familial Hypercholesterolemia," is published in the journal NEJM.
DOI: 10.1056/NEJMoa2004215