# Evinacumab bij homozygoot familiaire hypercholesterolemie: NEJM

*geplaatst 2020-08-20 · Cholesterol · The New England journal of medicine · doi 10.1056/NEJMoa2004215 · https://hartvaat.nl/2020/08/20/evinacumab-bij-homozygoot-familiaire-hypercholesterolemie-nejm/*

NEJM trial van evinacumab (ANGPTL3-remmer) bij homozygote FH. Eerste behandeling die LDL-verlaging biedt onafhankelijk van de LDL-receptor. Doorbraak voor de zwaarste FH.

## English: Evinacumab for Homozygous Familial Hypercholesterolemia.

This pivotal trial showed that evinacumab, an ANGPTL3 inhibitor, reduced LDL cholesterol by 47% in patients with homozygous familial hypercholesterolemia, a condition where conventional therapies including PCSK9 inhibitors are often ineffective due to absent LDL receptors. Evinacumab represents the first LDL-receptor-independent approach to cholesterol lowering.

## Abstract (original, from the publication)

BACKGROUND: Homozygous familial hypercholesterolemia is characterized by premature cardiovascular disease caused by markedly elevated levels of low-density lipoprotein (LDL) cholesterol. This disorder is associated with genetic variants that result in virtually absent (null-null) or impaired (non-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, a monoclonal antibody against ANGPTL3, has shown potential benefit in patients with homozygous familial hypercholesterolemia. METHODS: In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned in a 2:1 ratio 65 patients with homozygous familial hypercholesterolemia who were receiving stable lipid-lowering therapy 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. RESULTS: 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 (95% confidence interval [CI], -65.0 to -33.1; P<0.001); the between-group least-squares mean absolute difference in the LDL cholesterol level was -132.1 mg per deciliter (95% CI, -175.3 to -88.9; P<0.001). 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. CONCLUSIONS: 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 weeks. (Funded by Regeneron Pharmaceuticals; ELIPSE HoFH ClinicalTrials.gov number, NCT03399786.).

Auteurs: Frederick J Raal, Robert S Rosenson, Laurens F Reeskamp, G Kees Hovingh, John J P Kastelein, Paolo Rubba, Shazia Ali, Poulabi Banerjee, Kuo-Chen Chan, Daniel A Gipe, Nagwa Khilla, Robert Pordy, David M Weinreich, George D Yancopoulos, Yi Zhang, Daniel Gaudet

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Bron: The New England journal of medicine, https://doi.org/10.1056/NEJMoa2004215. Bijgewerkt 2026-07-03T13:27:53Z. Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.