PCSK9 inhibitor Evinacumab may significantly lower LDL cholesterol in FH: NEJM

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. 

"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