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Obicetrapib: Reversing the Tide of CETP Inhibitor Disappointments

John J P Kastelein1, Andrew Hsieh2, Mary R Dicklin3

  • 1NewAmsterdam Pharma B.V., Naarden, Netherlands.

Current Atherosclerosis Reports
|December 22, 2023
PubMed
Abstract

Insights

Obicetrapib, a novel cholesteryl ester transfer protein inhibitor, shows promise for treating dyslipidemia and atherosclerotic cardiovascular disease. Clinical trials demonstrate its ability to significantly lower atherogenic lipoproteins and raise HDL-C with a favorable safety profile.

Area of Science:

  • Cardiovascular Medicine
  • Pharmacology
  • Lipid Metabolism

Background:

  • Cholesteryl ester transfer protein (CETP) inhibitors have a complex history in cardiovascular outcomes trials.
  • Dyslipidemia and atherosclerotic cardiovascular disease (ASCVD) remain significant global health challenges.
  • Novel therapeutic strategies are needed to effectively manage lipid profiles and reduce cardiovascular risk.

Purpose of the Study:

  • To review the historical context of CETP inhibitor trials.
  • To introduce obicetrapib, a next-generation CETP inhibitor.
  • To discuss its potential in treating dyslipidemia and ASCVD.

Main Methods:

  • Review of historical cardiovascular outcomes trials of CETP inhibitors.
  • Description of obicetrapib's development and clinical trial data (Phase 1-3).
  • Evaluation of safety, tolerability, and lipid/lipoprotein effects in various treatment combinations.

Main Results:

  • Obicetrapib demonstrated significant reductions in LDL-C, non-HDL-C, apoB, and lipoprotein (a).
  • It also showed an increase in HDL-C, a key marker for cardiovascular health.
  • Phase 1 and 2 trials indicated an excellent safety and tolerability profile for obicetrapib.

Conclusions:

  • Obicetrapib is a promising oral, once-daily, low-dose CETP inhibitor.
  • It effectively lowers atherogenic lipoproteins and raises HDL-C.
  • Pivotal Phase 3 trials, including a cardiovascular outcomes trial, are ongoing to confirm its therapeutic potential for ASCVD.
Keywords:
Atherosclerotic cardiovascular disease (ASCVD)Cardiovascular outcomes trialCholesteryl ester transfer protein (CETP) inhibitorHigh-density lipoprotein cholesterol (HDL-C)Low-density lipoprotein cholesterol (LDL-C)Obicetrapib

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