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Updated: Aug 24, 2025
Cholesterol Efflux Assay
Published on: March 6, 2012
CSL112 (Apolipoprotein A-I [Human]) Strongly Enhances Plasma Apoa-I and Cholesterol Efflux Capacity in Post-Acute
C Michael Gibson1, Syed Hassan A Kazmi1, Serge Korjian1
1Division of Cardiovascular Medicine, Department of Medicine, 1859Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Insights
CSL112 rapidly increased cholesterol efflux capacity (CEC) in patients with acute myocardial infarction (AMI). This apoA-I therapy shows potential for atheroprotective benefits in AMI patients.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Biochemistry
Background:
- Cholesterol efflux capacity (CEC) is crucial for cardiovascular health and is impaired after acute myocardial infarction (AMI).
- CSL112, an intravenous preparation of apolipoprotein A-I (apoA-I) with phosphatidylcholine (PC), aims to enhance CEC and reduce recurrent cardiovascular events post-AMI.
Purpose of the Study:
- To analyze the pharmacokinetic (PK) and pharmacodynamic (PD) properties of CSL112 in patients following AMI.
- To evaluate the dose-dependent effects of CSL112 on CEC, apoA-I, and other relevant biomarkers.
Main Methods:
- A substudy of the AEGIS-I trial involving 63 AMI patients randomized to low-dose (2 g) or high-dose (6 g) CSL112, or placebo, receiving weekly infusions.
- PK/PD assessments included plasma apoA-I, PC, total and ABCA1-dependent CEC, lipids, lipoproteins, and inflammatory biomarkers.
Main Results:
- CSL112 administration led to rapid, dose-dependent increases in apoA-I, PC, and CEC, peaking around 2 hours post-infusion.
- CSL112 increased HDL-C but did not affect non-HDL-C, LDL-C, ApoB, or triglycerides.
- Renal function did not impact CSL112's PK/PD, and no dose-related effects on inflammatory biomarkers were observed.
Conclusions:
- CSL112 effectively and rapidly elevates CEC and apoA-I levels in AMI patients in a dose-dependent manner.
- The findings support CSL112's potential as an atheroprotective therapy for patients recovering from AMI.
Introduction:
Cholesterol efflux capacity (CEC) is impaired following acute myocardial infarction (AMI). CSL112 is an intravenous preparation of human plasma-derived apoA-I formulated with phosphatidylcholine (PC). CSL112 is intended to improve CEC and thereby prevent early recurrent cardiovascular events following AMI. AEGIS-I (ApoA-I Event Reducing in Ischemic Syndromes I) was a multicenter, randomized, double-blind, placebo-controlled, dose-ranging phase 2b study, designed to evaluate the hepatic and renal safety of CSL112. Here, we report an analysis of a pharmacokinetic (PK) and pharmacodynamic (PD) substudy of AEGIS-I.
Methods:
AMI patients were stratified by renal function and randomized 3:3:2 to 4, weekly, 2-hour infusions of low- and high-dose (2 g and 6 g) CSL112, or placebo. PK/PD assessments included plasma concentrations of apoA-I and PC, and measures of total and ABCA1-dependent CEC, as well as lipids/lipoproteins including high density lipoprotein cholesterol (HDL-C), non-HDL-C, low density lipoprotein cholesterol (LDL-C), ApoB, and triglycerides. Inflammatory and cardio-metabolic biomarkers were also evaluated.
Results:
The substudy included 63 subjects from AEGIS-I. CSL112 infusions resulted in rapid, dose-dependent increases in baseline corrected apoA-I and PC, which peaked at the end of the infusion (Tmax ≈ 2 hours). Similarly, there was a dose-dependent elevation in both total CEC and ABCA1-mediated CEC. Mild renal impairment did not affect the PK or PD of CSL112. CSL112 administration was also associated with an increase in plasma levels of HDL-C but not non-HDL-C, LDL-C, apoB, or triglycerides. No dose-effects on inflammatory or cardio-metabolic biomarkers were observed.
Conclusion:
Among patients with AMI, impaired CEC was rapidly elevated by CSL112 infusions in a dose-dependent fashion, along with an increase in apoA-I plasma concentrations. Findings from the current sub-study of the AEGIS-I support a potential atheroprotective benefit of CSL112 for AMI patients.
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