Obicetrapib-the Rebirth of CETP Inhibitors?

Curr Atheroscler Rep. 2024 Oct;26(10):603-608. doi: 10.1007/s11883-024-01231-5. Epub 2024 Aug 16.

Abstract

Purpose of review: To provide perspective on the current development status, and potential future role, of obicetrapib, a third-generation cholesterylester transfer protein (CETP) inhibitor. Obicetrapib has received recent attention following positive Phase II clinical trial data and initiation of Phase III trials for the treatment of dyslipidemia and atherosclerotic cardiovascular disease (ASCVD).

Recent findings: The ROSE and ROSE2 trials are Phase II studies that examined the lipid lowering effects of obicetrapib in patients on pre-existing high-intensity statin therapy. Obicetrapib significantly reduced key dyslipidemia biomarkers including low density lipoprotein cholesterol (LDL-C), Apolipoprotein B (Apo B), and non-high-density lipoprotein cholesterol (non-HDL-C) while increasing high-density lipoprotein cholesterol (HDL-C). Four phase III clinical trials, including a cardiovascular outcomes trial, are ongoing. Preliminary data for obicetrapib shows favorable effects on dyslipidemia, which could theoretically lead to a decrease in ASCVD clinical events. Short-term safety data in preliminary studies shows no significant safety signals.

Keywords: CETP; Cholesterylester transfer protein inhibitor; Lipid lowering; Low-density lipoprotein; Obicetrapib.

Publication types

  • Review

MeSH terms

  • Anticholesteremic Agents* / therapeutic use
  • Atherosclerosis / drug therapy
  • Cholesterol Ester Transfer Proteins* / antagonists & inhibitors
  • Dyslipidemias / blood
  • Dyslipidemias / drug therapy
  • Humans

Substances

  • Cholesterol Ester Transfer Proteins
  • Anticholesteremic Agents
  • CETP protein, human