Biological Basis and Proposed Mechanism of Action of CSL112 (Apolipoprotein A-I [Human]) for Prevention of Major Adverse Cardiovascular Events in Patients post Myocardial Infarction

Abstract Despite current standard of care treatment, the period shortly after acute myocardial infarction (AMI) is associated with particularly 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 which may be potentially addressed by the recent shift in focus away from raising levels of high-density lipoprotein cholesterol (HDL-C), to ones that optimize HDL function. Apolipoprotein A-I (apoA-I) is the major protein constituent of HDL and a key mediator of cholesterol efflux from macrophages within atherosclerotic plaque, a property which may convey therapeutic efficacy during the high-risk period. CSL112 is a novel formulation of human plasma-derived apolipoprotein A-I (apoA-I), reconstituted with phosphatidylcholine and stabilized with sucrose that is currently being evaluated in a phase 3 clinical trial (AEGIS-II) for the reduction of major adverse CV events (MACE) in the period of high-risk post AMI. Patients with diabetes mellitus are especially at high risk of recurrent MI, and are an enriched patient population in the AEGIS-II study. In this presentation, we provide an overview of the biological properties of CSL112 that contribute to its proposed mechanism of action for reducing rates of MACE post AMI. 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.