Rezafungin (CD101), a next-generation echinocandin: A systematic literature review and assessment of possible place in therapy

Abstract

Rezafungin is a novel echinocandin currently in phase 2 studies, differentiated by a long half-life that allows once-weekly dosing and a safety profile that allows higher doses. Several potential areas of use for rezafungin were identified.

Activity of a Long-Acting Echinocandin, Rezafungin, and Comparator Antifungal Agents Tested against Contemporary Invasive Fungal Isolates (SENTRY Program, 2016 to 2018)

“…Echinocandins have some important limitations, despite their proven safety and efficacy (9,15). Most notably, the daily parenteral dosing requirement complicates administration postdischarge in patients requiring extended therapy.…”

“…Although step-down therapy from an echinocandin to fluconazole may partially address the outpatient antifungal expenditure, it is complicated by the increasing rates of resistance to fluconazole among common species of Candida (1,7,9,14,16). Other potential drawbacks of the available echinocandins for clinical application are the use of a fixed dose irrespective of body size or species susceptibility (S) and emerging resistance mediated by mutations in the fks genes (15,17). It has been suggested that underdosing of echinocandins, coupled with poor penetration to certain body sites, may partially account for the emerging echinocandin resistance (15,18,19).…”

“…Other potential drawbacks of the available echinocandins for clinical application are the use of a fixed dose irrespective of body size or species susceptibility (S) and emerging resistance mediated by mutations in the fks genes (15,17). It has been suggested that underdosing of echinocandins, coupled with poor penetration to certain body sites, may partially account for the emerging echinocandin resistance (15,18,19). An echinocandin that could be safely administered at higher doses to ensure optimal pharmacokinetic (PK) and pharmacodynamic (PD) features and target attainment may facilitate outpatient therapy, reduce the hospital stay, and possibly delay or prevent the development of echinocandin resistance, thus becoming an important step toward improving the ability to effectively manage candidemia and IC (15,20).…”

“…Rezafungin (Cidara Therapeutics, Inc.) is a novel echinocandin that exhibits a prolonged half-life and that displays chemical stability in plasma, in aqueous solution, and at an elevated temperature (15,(21)(22)(23)(24)(25)(26)(27). The in vitro activity of rezafungin against Candida spp.…”

Lack of Effect of Rezafungin on QT/QTc Interval in Healthy Subjects

“…Rezafungin (CD101) is a new echinocandin antifungal agent in development to treat candidemia and invasive candidiasis and to prevent invasive fungal diseases caused by Candida , Aspergillus , and Pneumocystis spp among immunosuppressed patients, including those undergoing allogeneic blood and marrow transplantation and those receiving cytotoxic chemotherapy for hematologic malignancies . Echinocandins inhibit the synthesis of 1,3‐β‐D‐glucan, an essential component of the fungal cell wall, resulting in cell wall stress and death .…”