CSL112 is an apolipoprotein A1 (apoA-I) derived from human plasma, and is a component of high-density lipoprotein (HDL, known as the “good”) cholesterol. CSL112 removes plaque from the arteries, and helps facilitate the removal process (cholesterol efflux) of low-density lipoprotein (LDL, known as the “bad”) cholesterol from the body.
Published in the New England Journal of Medicine and simultaneously presented at the American College of Cardiology’s Annual Scientific Session in April 2024, the AEGIS-II trial examined whether infusions of CSL112 can lower the risk of patients experiencing recurrent cardiovascular events following an acute myocardial infarction, commonly known as a heart attack.
The AEGIS-II trial enrolled a total of 18,219 patients at 886 sites in 49 countries (including 508 patients from 31 sites in Canada). Adult patients with acute myocardial infarction, multivessel coronary artery disease, and additional cardiovascular risk factors (e.g., diabetes), were randomly assigned to receive either 6 g of CSL112 or a matching placebo through 4 weekly infusions, with the first dose administered within 5 days of first medical contact. The study’s primary endpoint was a composite of myocardial infarction, stroke, or death from cardiovascular causes.
Study results showed that, when compared to placebo, CSL112 did not demonstrate a statistically significant reduction in recurrent cardiovascular events. However, in a secondary analysis published in the Journal of the American College of Cardiology, the AEGIS-II investigators found that patients treated with CSL112 experienced fewer heart attacks at the 6-month mark compared to the control group. This suggests that apoA-I could play a part in reducing subsequent plaque disruption, and that the benefits of this treatment are worth exploring in future studies.
“While we didn’t see a benefit of CSL112 infusions on mortality, there did appear to be a favourable signal in reducing the risk of recurrent myocardial infarction,” said Dr. Shaun Goodman, CVC Co-Director. “I think there is a treatment effect supporting the cholesterol efflux hypothesis. We’re undertaking additional analysis of the trial database to try and identify which type of patient—for example, those with a particularly high LDL-cholesterol level—might realize a lower risk of recurrent cardiovascular events with CSL112 infusions.”
Dr. Shaun Goodman is a member of the AEGIS-II Executive Committee and is a co-author of both these publications. Faculty member Dr. Kevin Bainey served both as a Steering Committee member and a Canadian Site Investigator. The CVC’s clinical operations team (including Lyndsey Garrity, Kaitlynn Braulio, Kalli Belseck, and Tracy Temple,) skillfully managed the Canadian contributions to this study, and were ably supported by our monitoring team.
