Investigational apolipoprotein A-1 infusion therapy enhances cholesterol efflux
Two research projects, presented on posters at the AHA Scientific Sessions, shed light on the mechanism via which CSL112, a novel formulation of apolipoprotein A-1 (apoA-1), may reduce the high incidence of early recurrent cardiovascular events seen in patients who have experienced a myocardial infarction.
Apolipoprotein A-I (apoA-I) is the primary functional component of high-density lipoprotein (HDL). In this new formulation, apoA-I is purified from human plasma and reconstituted to form HDL particles suitable for intravenous infusion. It has been shown that the infusion of CSL112 rapidly elevates markers of reverse cholesterol transport. CSL112 is being developed as a therapy to rapidly stabilise atherosclerotic plaque, thereby reducing the high risk of early recurrent CV events.
In a poster titled ‘CSL112 enhances cholesterol efflux equally in patients with high and low HDL functionality’, Andreas Gille presented data from 93 healthy subjects and 44 patients with stable atherosclerotic disease, in which CSL112 caused strong and quantitatively similar elevation in cholesterol efflux, independent of baseline efflux activity. Patients with cardiovascular disease are known to have lower cholesterol efflux capacity, and these data suggest that CSL112 will effectively elevate efflux in patients with impaired HDL function.
Svetlana Didichenko presented a poster titled ‘Mechanism of HDL remodelling induced by CSL112. In vitro studies showed that infused CSL112 is rapidly remodelled to form pre-β1 HDL, a type of HDL with superior cholesterol efflux capacity, and that this remodelling accounts for the immediate and robust increase in cholesterol efflux capacity observed upon infusion of CSL112.
These findings suggest that CSL112 can increase cholesterol efflux, the first step in reverse cholesterol transport. This may translate into reduction of early recurrent CV events after myocardial infarction.
CSL Behring has announced the start of AEGIS-I, a Phase 2b clinical study of a short series of weekly infusions with CSL112. This global, randomised, placebo-controlled, dose-ranging study will investigate the safety and tolerability of multiple dose administrations of CSL 112 in 1200 patients who experienced acute myocardial infarction or heart attack. Secondary outcome measures include time-to-first occurrence of a major adverse CV event (MACE).