Evinacumab: Anti-ANGPTL3 (angiopoietin-like protein 3) monoclonal antibody Treatment of homozygous familial hypercholesterolemia Treatment of dyslipidemia and cardiovascular disease

B. A. Warden, P. B. Duell

Research output: Contribution to journalArticlepeer-review

Abstract

The family of angiopoietin-like (ANGPTL) proteins consists of 8 members (ANGPTL1-8) that have disparate effects on physiology. Three members of the family, ANGPTL3, ANGPTL4 and ANGPTL8, modulate lipoprotein metabolism. Data from epidemiologic studies as well as investigations of the effects of reduced ANGPTL3 activity on lipoprotein metabolism and atherosclerotic cardiovascular disease (ASCVD) in humans and animal models suggest that inhibition of ANGPTL3 activity is likely associated with reduced risk of ASCVD. Data from phase I to III clinical trials demonstrate that treatment with evinacumab, a fully human monoclonal antibody directed against ANGPTL3, effectively lowers plasma triglycerides and low-density lipoprotein cholesterol (LDL-C) by roughly half with minimal side effects. Remarkably, even patients with refractory severe hypercholesterolemia caused by homozygous familial hypercholesterolemia (HoFH) have achieved a 49% reduction in LDL-C during treatment with evinacumab. The drug is under investigation for treatment of a variety of lipid disorders, the most developed of which is for reduction of LDL-C in patients with HoFH. In the meantime, patients with HoFH will be anxiously awaiting the potential clinical availability of this much-needed new LDL-C-lowering medication.

Original languageEnglish (US)
Pages (from-to)619-631
Number of pages13
JournalDrugs of the Future
Volume45
Issue number9
DOIs
StatePublished - Sep 2020

Keywords

  • ANGPTL3
  • Evinacumab
  • Familial hypercholesterolemia
  • Hypertriglyceridemia
  • Lipid-lowering therapy
  • Monoclonal antibody
  • REGN-1500

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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