Evinacumab Found to Lower LDL-C in Homozygous Familial Hypercholesterolemia

The addition of evinacumab to stable lipid-lowering therapy was found to reduce levels of LDL-C in patients with homozygous familial hypercholesterolemia.

The addition of evinacumab to stable lipid-lowering therapy was found to reduce levels of low-density lipoprotein-cholesterol (LDL-C) in patients with homozygous familial hypercholesterolemia, according to the results of a double-blind, placebo-controlled, phase 3 clinical trial published in the New England Journal of Medicine.

In this study, 65 patients with homozygous familial hypercholesterolemia who were receiving the maximum dose of stable lipid-lowering therapy were recruited at 30 sites in 11 countries between 2018 and 2019. Participants were randomly assigned to receive in a 2:1 ratio the angiopoietin-like 3 monoclonal antibody, evinacumab (n=43; 15 mg/kg) or placebo (n=22) intravenously every month for 24 weeks. The study’s primary outcome was the percent change from baseline in LDL-C level after 24 weeks of treatment.

The treatment and placebo groups were well balanced for demographic characteristics, 82% of participants had genetically confirmed homozygous familial hypercholesterolemia, and 94% were on statins. At baseline, mean LDL-C was 250 mg/dL and 247 mg/dL in the treatment and placebo groups, respectively.

After 24 weeks, there was a 47.1% reduction in LDL-C levels in the group receiving evinacumab and a 1.9% increase in LDL-C in the group receiving placebo, compared with baseline levels. The between group least-squares mean difference was -49.0 percentage points (95% CI, -65.0 to -33.1; P <.001), and the absolute difference was -132 mg/dL (-175 to -89 mg/dl; P <.001).

The initial decrease in LDL-C was observed starting at week 2 in the evinacumab group, and was maintained throughout the study duration. The change in LDL-C levels was comparable in patients treated with different background therapies (statins, ezetimibe, lomitapide, proprotein convertase subtilisin–kexin type 9 inhibitors, or apheresis).

At 24 weeks, participants receiving evinacumab vs placebo had greater percent changes of apolipoprotein B (mean difference, -36.9; 95% CI, -48.6 to -25.2; P <.001), non-high-density lipoprotein cholesterol (mean difference, -51.7; 95% CI, -64.8 to -38.5; P <.001), and total cholesterol (mean difference, -48.4; 95% CI, -58.7 to -38.1; P <.001).

Adverse events were observed in 66% and 81% of participants in the evinacumab and placebo groups, respectively, none of which led to treatment discontinuation. No antidrug antibodies were detected. Serious adverse events (urosepsis and a suicide attempt) were reported by 2 participants in the evinacumab group. An influenza-like illness was reported by 11% of patients in the evinacumab group.

Study limitations include its short duration and small sample sizes, which prevented investigators from assessing long-term safety of the treatment.

“[E]vinacumab substantially lowered LDL cholesterol levels in patients with homozygous familial hypercholesterolemia, regardless of the degree of their LDL-receptor function,” concluded the study authors.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Raal F J, Rosenson R S, Reeskamp L F, et al. Evinacumab for homozygous familial hypercholesterolemia. N Engl J Med. 2020;383(8):711-720. doi:10.1056/NEJMoa2004215