AbstractBackgroundRezafungin is a next-generation, once-weekly echinocandin in development for treatment of candidaemia and invasive candidiasis (IC), and for prevention of invasive fungal diseases caused byCandida,Aspergillus, andPneumocystisin allogeneic blood and marrow transplant recipients (Figure 1). ReSTORE (NCT03667690) is a global, double-blind, double-dummy, 1:1 randomized, controlled, Phase 3 non-inferiority trial that evaluated the efficacy and safety of rezafungin once weekly (QWk) versus caspofungin once daily (QD) in patients with candidaemia and/or IC. This analysis of the completed ReSTORE trial was conducted to evaluate outcomes by baseline pathogen and susceptibility.MethodsIn ReSTORE, adults (≥18 y) with systemic signs and mycological confirmation of candidaemia and/or IC received either rezafungin QWk (400 mg Week 1, then 200 mg QWk) or caspofungin QD for ≥14 days (up to 4 weeks) with optional oral fluconazole step-down in the caspofungin arm. The primary endpoints were global cure at day (D)14 (per Data Review Committee confirmation of investigator-assessed clinical cure [and radiological cure for IC) + mycological eradication]) and all-cause mortality (ACM) at D30 (Figure 2). Secondary endpoints included mycological eradication at D14. For this analysis, D14 global cure and mycological eradication by treatment group were analysed byCandidaspecies and in vitro susceptibility at baseline (CLSI broth microdilution MIC values; M27 Ed4) (Figure 3).ResultsA total of 204Candidaisolates were recovered in 187 patients across both treatment groups. Of the 204 isolates,Candida albicanswas the most common species, followed byCandida glabrata,Candida tropicalis, andCandida parapsilosis; 61% of all baseline isolates were non-albicansCandida(Figure 3). The rates of D14 global cure and mycological eradication by pathogen are shown in Tables 1 and 2. Overall, outcomes byCandidaspecies and MIC did not appear to be affected by MIC values for either rezafungin or caspofungin (Table 3).ConclusionsRezafungin was efficacious across multipleCandidaspecies in the Phase 3 ReSTORE trial that demonstrated non-inferiority of rezafungin to caspofungin. There was no clear correlation between increased MIC values and clinical outcomes.Figure 1.Rezafungin Phase 3 program.Figure 2.Study design of ReSTORE (NCT03667690).Figure 3.Candida species distribution and susceptibility at baseline in ReSTORE.Table 1.Global response of cure at day 14 by most frequently isolatedCandidaspecies at baseline by treatment group (mITT)Table 2.Mycological response of eradication at day 14 by most frequently isolatedCandidaspecies at baseline by treatment groupTable 3.Outcomes at day 14 by CLSI MIC values for most frequently isolated Candida species at baseline, by treatment group (mITT)aNumerator/denominator is the number of subjects with listed response at day 14/the number of subjects with the correspondingCandidapathogen and MIC value for the respective treatment, as indicated by headers, at baseline. Not all isolates had MIC data.