Rezafungin Versus Caspofungin in Candidaemia and Invasive Candidiasis: A Post Hoc Pooled Analysis of Phase 2 and Phase 3 Trials.

Abstract

Background: The efficacy and safety of rezafungin in invasive candidiasis (IC) and candidaemia was demonstrated in the Phase 2 STRIVE and Phase 3 ReSTORE trials, and an additional cohort of patients in ReSTORE from China (ReSTORE China).

Objectives: This post hoc analysis is the first time that combined data from all double-blind, randomised Phase 2 and 3 rezafungin trials have been evaluated. Outcomes were comprehensively assessed across a large, diverse population.

Methods: Data were assessed from adults with candidaemia/IC in STRIVE (NCT02734862) and ReSTORE (NCT03667690) (including the China extension cohort) who received weekly rezafungin 400/200 mg or daily caspofungin 70/50 mg for ≤ 4 weeks. Efficacy was assessed in the modified intent-to-treat population. Endpoints were Day 30 all-cause mortality (ACM, primary), mycological response at Days 5 and 14 (secondary) and time to negative blood cultures (TTNBC, secondary). Treatment-emergent adverse events were assessed in the safety population.

Results: Overall, 372 patients were included (rezafungin 179; caspofungin 193). Day-30 ACM was 20% (33/161) for rezafungin versus 22% (39/178) for caspofungin (weighted difference, -2.4% [95% confidence interval -11.2 to 6.4]). Day-5 and Day-14 mycological eradication rates were 73% and 70% for rezafungin versus 65% and 68% for caspofungin, respectively. Median TTNBC was shorter for rezafungin than for caspofungin (23.1 versus 36.7 h, respectively; p = 0.0073). Adverse-event profiles were generally similar across treatments.

Conclusions: This pooled analysis of Phase 2 and Phase 3 data, including the China extension cohort, supports the efficacy and safety of rezafungin. Rezafungin was non-inferior to caspofungin, with earlier mycological eradication.