Biological basis and proposed mechanism of action of CSL112 (apolipoprotein A-I [human]) for prevention of major adverse cardiovascular events in patients with myocardial infarction.

Abstract

Despite current standard of care treatment, the period shortly after acute myocardial infarction (AMI) is associated with high residual cardiovascular (CV) risk, with high rates of recurrent AMI and CV death in the first 90 days following the index event. This represents an area of high unmet need that may be potentially addressed by novel therapeutic agents that optimize high-density lipoprotein cholesterol (HDL-C) function rather than increase HDL-C concentrations. Apolipoprotein A-I (apoA-I) is the major constituent of HDL and a key mediator of cholesterol efflux from macrophages within atherosclerotic plaque, a property especially relevant during the high-risk period immediately following an AMI when cholesterol efflux capacity is found to be reduced. CSL112 is a novel formulation of human plasma-derived apolipoprotein A-I (apoA-I), currently being evaluated in a Phase 3 clinical trial (AEGIS-II) for the reduction of major adverse CV events in the 90-day high-risk period post-AMI. In this review, we provide an overview of the biological properties of CSL112 that contribute to its proposed mechanism of action for potential therapeutic benefit. These properties include rapid and robust promotion of cholesterol efflux from cells abundant in atherosclerotic plaque, in addition to anti-inflammatory effects, which together, may have a stabilizing effect on atherosclerotic plaque. We provide a detailed overview of these mechanisms, in addition to information on the composition of CSL112 and how it is manufactured.

• Authors: Serge Korjian, Syed Hassan A Kazmi, Gerald Chi, Arzu Kalayci, Jane J Lee, Usama Talib, Samuel D Wright, Danielle Duffy, Bronwyn A Kingwell, Roxana Mehran, Paul M Ridker, C Michael Gibson
• Journal: European heart journal. Cardiovascular pharmacotherapy (Eur Heart J Cardiovasc Pharmacother) Vol. 9 Issue 4 Pg. 387-398 (06 02 2023) ISSN: 2055-6845 [Electronic] England
• PMID: 36787889 (Publication Type: Review, Journal Article)
• Copyright: © The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.

Chemical References

• CSL112
• Cholesterol
• Apolipoprotein A-I
• Lipoproteins, HDL

Topics

• Humans
• Cholesterol
• Apolipoprotein A-I
• Plaque, Atherosclerotic (drug therapy)
• Lipoproteins, HDL (adverse effects)
• Myocardial Infarction (drug therapy, prevention & control)