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.).