The Upcoming Antifungal Drugs in Clinical Development for the Treatment of Invasive Candidiasis

Background: Invasive candidiasis (IC) is a major cause of morbidity and mortality among hospitalized patients, and treatment success relies on early diagnosis and prompt initiation of an appropriate antifungal agent. The increasing rates of resistance to first-line antifungal agents (azoles, echinocandins, and polyenes), along with changes in the epidemiology of IC and the spread of multidrug-resistant C. auris , pose further challenges for the management of IC. Limited therapeutic options and routes of administration, drug–drug interactions, and drug toxicities of commonly utilized antifungals further complicate management in the acute hospital setting and create barriers for long-term outpatient treatment. This article provides a review of the current literature on the upcoming antifungal agents that are being actively investigated as treatment options for invasive candidiasis, including those in early- and late-stage clinical development. Areas Covered: We will discuss the spectrum of activity of novel antifungal agents, mechanisms or resistance, pertinent in vivo and vitro data, as well as data from the clinical trials evaluating efficacy and safety of novel antifungals. Expert Opinion: Rezafungin holds promise as an excellent option for outpatient antimicrobial therapy programs due to its favorable safety profile and convenient once-weekly dosing. Ibrexafungerp has broad-spectrum antifungal activity, including activity against fluconazole- and echinocandin-resistant Candida spp. and is available in an oral formulation, making it an attractive option for step-down therapy after treatment with echinocandins or as an alternative to echinocandins. Fosmanogepix has a novel mechanism of action, a favorable side-effect profile, and a broad spectrum of clinical activity. However, further data from clinical trials are necessary to further establish its role in the management of invasive candidiasis. The role of agents in early clinical development, including BAL2062 and ATI2307, as well as repurposed agents with antifungal activity, such as miltefosine, in the management of invasive candidiasis remains to be determined. Keywords: invasive candidiasis, fosmanogepix, rezafungin, ibrexafungerp, Candida glabrata , Candida auris , fluconazole resistance, echinocandins, BAL2062, ATI2307, miltefosine