Clinical Pharmacokinetics and Pharmacodynamics of CSL112.

Cardiovascular diseases are the leading cause of death worldwide. Although there have been substantial advances over the last decades, recurrent adverse cardiovascular events after myocardial infarction are still frequent, particularly during the first year of the index event. For decades, high-density lipoprotein (HDL) has been among the therapeutic targets for long-term prevention after an ischemic event. However, early trials focusing on increasing HDL circulating levels showed no improvement in clinical outcomes. Recently, the paradigm has shifted to increasing the functionality of HDL rather than its circulating plasma levels. For this purpose, apolipoprotein-AI-based infusion therapies have been developed, including reconstituted HDL, such as CSL112. During the last decade, CSL112 has been extensively studied in Phase 1 and 2 trials and has shown promising results. In particular, CSL112 has been studied in the Phase 2b AEGIS trial exhibiting good safety and tolerability profiles, which has led to the ongoing large-scale Phase 3 AEGIS-II trial. This systematic overview will provide a comprehensive summary of the CSL112 drug development program focusing on its pharmacodynamic, pharmacokinetic, and safety profiles.