Novel Therapeutic Approaches to Invasive Candidiasis: Considerations for the Clinician

Abstract

Invasive candidiasis (IC), due to the yeast pathogen Candida, is still a major cause of in-hospital morbidity and mortality. The limited number of antifungal drug classes and the emergence of multi-resistant Candida species, such as Candida auris and some Candida glabrata isolates, is concerning. However, recent advances in antifungal drug development provide promising perspectives for the therapeutic approach of IC. Notably, three novel antifungal agents, currently in Phase II/III clinical trials, are expected to have an important place for the treatment of IC in the future. Rezafungin is a novel echinocandin with prolonged half-life. Ibrexafungerp and fosmanogepix are two first-in-class antifungal drugs with broad spectrum activity against Candida spp., including C. auris and echinocandin-resistant species. These novel antifungal agents also represent interesting alternative options because of their acceptable oral bioavailability (ibrexafungerp and fosmanogepix) or their large interdose interval (once weekly intravenous administration for rezafungin) for prolonged and/or outpatient treatment of complicated IC. This review discusses the potential place of these novel antifungal drugs for the treatment of IC considering their pharmacologic properties and their preclinical and clinical data.

Keywords:

• Candida
• candidemia
• rezafungin
• ibrexafungerp
• fosmanogepix
• oteseconazole
• tetrazoles
• T-2307
• antifungal therapy

Disclosure

FL has received research funding from Gilead, MSD, Pfizer and Novartis, has participated to advisory boards of Gilead, MSD and Pfizer, and has received honoraria for conferences from Gilead and Mundipharma. All contracts were made with and fees paid to his institution (CHUV). The author reports no other conflicts of interest in this work.

Additional information

Funding

There was no dedicated funding for this work.