Rezafungin Versus Caspofungin for the Treatment of Candidemia and Invasive Candidiasis: Results from the Double-blind, Randomized, Phase 3 ReSTORE Trial Including the China Extension Study

Abstract

Background. Rezafungin is approved for use in adults with candidemia and/or invasive candidiasis (IC) based on data from the ReSTORE trial (NCT03667690), which demonstrated noninferior efficacy to caspofungin. For regulatory purposes, an additional cohort of patients from China was recruited to ReSTORE. Here, we compared rezafungin and caspofungin in patients with candidemia and/or IC through analysis of the ReSTORE global data plus the China extension study. Methods. Adults with candidemia/IC were randomized (1:1) to receive weekly rezafungin (400/200 mg) or daily caspofungin (70/50 mg) for ≤28 days. Noninferiority was concluded for primary efficacy endpoints if the upper bound of the 95% confidence interval (CI) was below 20% for Day 30 all-cause mortality and if the weighted lower bound was above −20% for Day 14 global cure. Additional efficacy outcomes and safety were evaluated. Results. Overall, 246 patients were randomized (122 rezafungin and 124 caspofungin). Noninferiority was demonstrated for both primary endpoints. Day 30 all-cause mortality was 25.2% and 24.8% (treatment difference 0.4%; 95% CI −10.8, 11.6) and Day 14 global cure was 56.5% and 57.3% (weighted treatment difference −1.0%; 95% CI −13.5, 11.6) with rezafungin versus caspofungin, respectively. Day 5 mycological eradication was numerically higher (68.7% vs 63.2%) and time to negative blood culture was numerically shorter (median 26.5 vs 38.8 h). Safety was comparable between groups; 53.3% (64/120; rezafungin) and 53.7% (66/123; caspofungin) of patients experienced serious adverse events. Conclusions. This analysis confirmed the overall efficacy and safety of rezafungin demonstrated in ReSTORE, with early efficacy related to front-loaded exposure.