Acebilustat (CTX-4430): A Comprehensive Review of its Pharmacology, Clinical Development, and Therapeutic Potential

I. Executive Summary

Acebilustat, formerly known as CTX-4430, is an orally administered small molecule drug designed as an inhibitor of Leukotriene A4 Hydrolase (LTA4H). Its primary pharmacological action is to reduce the biosynthesis of Leukotriene B4 (LTB4), a potent pro-inflammatory mediator, thereby aiming to exert anti-inflammatory effects in various pathological conditions. Initially developed with a focus on cystic fibrosis (CF), Acebilustat garnered Orphan Drug Designation from both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for this indication. However, despite promising early-phase biomarker data, the pivotal Phase 2 EMPIRE-CF trial (NCT02443688) did not achieve its primary efficacy endpoint related to lung function improvement, although some trends in reducing pulmonary exacerbations were noted in specific patient subgroups. This outcome significantly impacted its development trajectory for CF.