New Therapeutic Approaches for Familial Hypercholesterolemia

Annu Rev Med. 2018 Jan 29:69:113-131. doi: 10.1146/annurev-med-051215-030943.

Abstract

Familial hypercholesterolemia (FH) is a common genetic condition characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C), premature atherosclerotic cardiovascular disease, and considerable unmet medical need with conventional LDL-C-lowering therapies. Between 2012 and 2015, the US Food and Drug Administration approved four novel LDL-C-lowering agents for use in patients with FH based on the pronounced LDL-C-lowering efficacy of these medicines. We review the four novel approved agents, as well as promising LDL-C-lowering agents in clinical development, with a focus on their mechanism of action, efficacy in FH cohorts, and safety.

Keywords: LDL; lomitapide; low-density lipoprotein; mipomersen; proprotein convertase subtilisin/kexin 9.

Publication types

  • Review

MeSH terms

  • Angiopoietin-like Proteins / antagonists & inhibitors
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Anticholesteremic Agents / therapeutic use*
  • Benzimidazoles / therapeutic use
  • Caproates / therapeutic use
  • Cholesterol Ester Transfer Proteins / antagonists & inhibitors
  • Dicarboxylic Acids / therapeutic use
  • Fatty Acids / therapeutic use
  • Genetic Therapy
  • Humans
  • Hyperlipoproteinemia Type II / therapy*
  • Oligonucleotides / therapeutic use
  • RNA, Small Interfering / therapeutic use
  • Receptors, LDL / genetics
  • Treatment Outcome

Substances

  • ALN-PCS
  • Angiopoietin-like Proteins
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Anticholesteremic Agents
  • BMS201038
  • Benzimidazoles
  • Caproates
  • Cholesterol Ester Transfer Proteins
  • Dicarboxylic Acids
  • Fatty Acids
  • LDLR protein, human
  • Oligonucleotides
  • RNA, Small Interfering
  • Receptors, LDL
  • 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
  • mipomersen
  • gemcabene
  • evolocumab
  • alirocumab