Post-AMI Infusion of Human Apolipoprotein A-1 (CSL112) Strongly Boosts Impaired Cholesterol Efflux Capacity

Infusion of CSL112, an investigational human plasma-derived apolipoprotein A-I (apoA-I) formulated with phosphatidylcholine (PC), rapidly and strongly elevated impaired cholesterol efflux capacity (CEC) following acute myocardial infarction (AMI), according to a 63-subject sub-study from the randomized, double-blind, saline placebo-controlled, dose ranging Phase IIb AEGIS-I study. CSL112 is intended to improve CEC and thereby reduce the incidence of early recurrent cardiovascular events following AMI.

AMI patients were stratified by renal function and randomized to four weekly two-hour infusions of low- and high-dose (2 g and 6 g) CSL112 or placebo. CSL112 infusions resulted in rapid, dose-dependent increases in baseline corrected apoA-I and PC, which peaked at the end of the two-hour infusion. Similarly, there was an immediate, strong, dose-dependent elevation in both total CEC and ABCA1-mediated CEC relative to baseline. Mild renal impairment did not affect the pharmacokinetics (PK) or pharmacodynamics (PD) of CSL112.

Additionally, following CSL112 administration, there were rapid, dose-dependent increases in plasma HDL-C levels, with a broad peak at two to six hours and gradual decline over approximately 48 hours (2 g infusion) or 96 hours (6 g infusion). There were no increases in the atherogenic lipids/lipoproteins non-HDL-C, LDL-C or apoB following infusion of CSL112. No dose-effects on inflammatory or cardio-metabolic biomarkers were observed.

These data demonstrate that four weekly infusions of CSL112 have a sustained impact on CEC, as well as support the selection of the 6 g dose for further development, the investigators concluded.