Evinacumab for treatment of familial hypercholesterolemia

Bruce A. Warden, P. Barton Duell

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Introduction: Familial hypercholesterolemia (FH) is characterized by lifelong elevation of low-density lipoprotein cholesterol (LDL-C), early onset coronary atherosclerosis, and premature death. FH is underdiagnosed and undertreated, but requires aggressive LDL-C-lowering to prevent complications. Current treatment strategies such as lifestyle modification and numerous LDL-C-lowering medications are often insufficient to achieve lipid goals in FH. Areas covered: Angiopoietin-like 3 protein (ANGPTL3) is intricately involved in lipid metabolism. Loss-of-function mutations in ANGPTL3 are associated with panhypolipidemia and reduced coronary atherosclerosis. Evinacumab, a fully human monoclonal antibody, inhibits ANGPTL3 and reduces multiple lipoprotein fractions ~50%, including LDL-C. The use of evinacumab within the FH population is described as well as its regulatory journey to an approved therapeutic. Expert opinion: Evinacumab, with its capacity to lower multiple lipoprotein fractions, particularly LDL-C, independently of LDLR function has potential to revolutionize treatment for FH patients. Current FDA-approval is only for homozygous FH (HoFH), arguably the most impactful indication, but use in other lipid disorders is under investigation. The short-term tolerability of evinacumab is very good, with infrequent, mild, and transient adverse events; however, long-term safety data are needed. The high cost and requirement for intravenous administration may limit adoption of evinacumab, but dramatic LDL-C-lowering and need for new therapeutic options for HoFH will drive interest.

Original languageEnglish (US)
Pages (from-to)739-751
Number of pages13
JournalExpert Review of Cardiovascular Therapy
Volume19
Issue number8
DOIs
StatePublished - 2021

Keywords

  • ANGPTL3
  • evinacumab
  • familial hypercholesterolemia
  • FH
  • homozygous FH
  • lipid-lowering therapy
  • Monoclonal antibody

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine

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