Outcomes by Candida spp. in the ReSTORE Phase 3 trial of rezafungin versus caspofungin for candidemia and/or invasive candidiasis

Abstract

Rezafungin is a long-acting, intravenously administered echinocandin for the treatment of candidemia and invasive candidiasis (IC). Non-inferiority of rezafungin vs caspofungin for the treatment of adults with candidemia and/or IC was demonstrated in the Phase 3 ReSTORE study based on the primary endpoints of day 14 global cure and 30-day all-cause mortality. Here, an analysis of ReSTORE data evaluating efficacy outcomes by baseline Candida species is described. Susceptibility testing was performed for Candida species using the Clinical and Laboratory Standards Institute reference broth microdilution method. There were 93 patients in the modified intent-to-treat population who received rezafungin; 94 received caspofungin. Baseline Candida species distribution was similar in the two treatment groups; C. albicans (occurring in 41.9% and 42.6% of patients in the rezafungin and caspofungin groups, respectively), C. glabrata (25.8% and 26.6%), and C. tropicalis (21.5% and 18.1%) were the most common pathogens. Rates of global cure and mycological eradication at day 14 and day 30 all-cause mortality by Candida species were comparable in the rezafungin and caspofungin treatment groups and did not appear to be impacted by minimal inhibitory concentration (MIC) values for either rezafungin or caspofungin. Two patients had baseline isolates with non-susceptible MIC values (both in the rezafungin group: one non-susceptible to rezafungin and one to caspofungin, classified as intermediate); both were candidemia-only patients in whom rezafungin treatment was successful based on the day 30 all-cause mortality endpoint. This analysis of ReSTORE demonstrated the efficacy of rezafungin for candidemia and IC in patients infected with a variety of Candida species.

In Vitro Activitiy of Rezafungin in Comparison with Anidulafungin and Caspofungin against Invasive Fungal Isolates (2017 to 2022) in China

“…Anidulafungin and rezafungin, which have been approved by the FDA, are still undergoing clinical trials in China. In our study, both anidulafungin and rezafungin were not inferior in activity when compared to the approved agent caspofungin, which is consistent with other published data [ 28 , 29 ]. The performance of the three tested echinocandins varied against different species, suggesting a different choice may be appropriate for different species, irrespective of other conditions.…”

A Mini-Review of In Vitro Data for Candida Species, Including C. auris, Isolated during Clinical Trials of Three New Antifungals: Fosmanogepix, Ibrexafungerp, and Rezafungin

“…Mycological eradiation by day 5 occurred in 73% of those treated with rezafungin and 65% of those with caspofungin. An analysis of ReSTORE clinical outcomes data by baseline Candida species and in vitro susceptibility results has recently been published (Table 4) [73]. Only two patients in this study had baseline isolates that had non-susceptible MIC results to both rezafungin and caspofungin.…”