Physicians' Academy for Cardiovascular Education

Angiopoietin-like protein 3 inhibitor reduces LDL-c in homozygous FH

News - Mar. 31, 2020

Evinacumab Significantly Reduces LDL-C In Patients With Homozygous Familial Hypercholesterolemia

Presented at ACC.20 by Prof. Frederick Raal, PhD (Johannesburg, South Africa)

Introduction and methods

Homozygous Familial Hypercholesterolemia (HoFH) is a genetic disorder usually caused by loss of function mutations in the LDL receptor. Standard lipid-lowering therapies, such as statins and PCSK9 inhibitors, act mainly by the upregulation of LDL receptor function. Most HoFH patients are unresponsive or respond poorly to these therapies. Evinacumab is a fully human monoclonal antibody inhibitor of angiopoietin-like protein 3 (ANGPTL3) that reduces LDL-c independent of the LDL receptor.

This pivotal phase 3 trial evaluated the safety and efficacy of evinacumab in HoFH patients ≥12 years of age on stable maximally tolerated lipid-lowering therapies with LDL-c ≥70 mg/dL. Patients were randomized 2:1 to receive either evinacumab 15 mg/kg IV every 4 weeks (n=43) or placebo IV every 4 weeks (n=22). There was a double-blind treatment period of 24 weeks followed by an open-label treatment period of 24 weeks in which all patients received evinacumab.

The primary endpoint was the percentage change in calculated LDL-c from baseline to week 24 during the double-blind treatment period.

Main results


This study showed that evinacumab significantly reduces LDL-c in patients with HoFH, regardless of LDL receptor function. Furthermore, evinacumab was generally well-tolerated. Evinacumab could therefore be an effective treatment option for HoFH patients who have high LDL-c levels despite being on multiple lipid-lowering therapies. The long-term safety of evinacumab will be further investigated in the open-label treatment period of the trial.


The results that evinacumab rapidly reduces LDL-c in patients who do not respond to PCSK9 inhibitors and that these reductions were maintained over the course of the therapy are impressive, according to discussant Eileen Handberg, PhD (Gainesville, FL, USA). Information about the effect of evinacumab in patients with different genotypes is very important in moving this field forward, as stated by Handberg. She further mentioned that long-term safety of the studied drug is extremely important, as these patients will need to use medications over the course of a lifetime. In future studies it would be interesting and important to investigate whether evinacumab could also work as a stand-alone therapy, instead of an additive to other lipid-lowering therapies.

- Our coverage of ACC.20 is based on the information provided during the congress –

Watch a video by prof. Raal

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