The distinctive pharmacokinetic profile of rezafungin, a long-acting echinocandin developed in the era of modern pharmacometrics.

Abstract

Echinocandin drugs are the current first-line therapy for fungal infections caused by Candida spp. Most patients require once-daily intravenous (IV) administration in a hospital or outpatient setting for treatment, which may negatively impact their quality of life and stress healthcare resources. Similar to other echinocandins, the novel FDA-, EMA-, and Medical and Healthcare Products Regulatory Agency-approved echinocandin, rezafungin (CD101), exhibited strong antifungal activity against several fungal pathogens and a low drug-drug interaction liability, which are important for medically complex patients. A pharmacometric-based approach has been adopted throughout the development of rezafungin, which contrasts with older echinocandins where dosing regimens were largely derived empirically, and only recently based on pharmacometric guidance. This state-of-the-art approach used model-based simulations incorporating pre-clinical and clinical data as it became available to optimize the dosing regimen for rezafungin. The enhanced stability of the molecular structure and the safety profile of rezafungin allow for the administration of once-weekly IV doses, compared to the daily dosing requirement for other echinocandin drugs, with this distinctive pharmacokinetic profile of rezafungin resulting in a front-loaded dosing regimen with high exposures early in therapy for enhanced fungal killing. The long shelf-life of rezafungin makes this echinocandin more flexible in terms of storage and manufacturing. Demonstrated across clinical development, rezafungin may provide patients with next-generation first-line antifungal treatment for the treatment of candidaemia and invasive candidiasis.