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.

Keywords: Candida species; antifungal therapy; candidemia; echinocandin; invasive candidiasis.

Fig 1

Baseline Candida spp. pathogens in the rezafungin and caspofungin treatment groups (mITT population). Data were calculated from 204 identified infections in 187 patients (rezafungin, n = 93; caspofungin, n = 94). All unique pathogens from the cultures collected within 96 hours prior to randomization or prior to the first dose of the study drug after randomization were summarized. Seventeen patients had multiple isolates at baseline: rezafungin treatment group (no. of patients): C. glabrata and C. tropicalis (3); C. albicans and C. glabrata (1); Candida dubliniensis and C. glabrata (1), Candida guilliermondii and C. tropicalis (1); C. parapsilosis and C. tropicalis (1); caspofungin treatment group: C. albicans and C. glabrata (3); C. albicans and C. tropicalis (3); C. glabrata and C. tropicalis (2); C. albicans and C. dubliniensis (1); C. glabrata and C. krusei (1).