Efficacy of Rezafungin in Prophylactic Mouse Models of Invasive Candidiasis, Aspergillosis, and Pneumonia.

Antifungal prophylaxis is recommended to prevent invasive fungal disease caused by spp., spp., and in patients at risk for opportunistic infections, such as allogeneic blood or marrow transplant recipients, patients with hematological disease undergoing chemotherapy, or patients on immunosuppressive therapies. Current approaches to antifungal prophylaxis require multiple agents to cover these key fungi. Rezafungin, a novel echinocandin designed for next-generation properties (e.g., greater stability and long-acting pharmacokinetics for once-weekly dosing), has demonstrated activity against and spp. and efficacy against spp. biofilms. Rezafungin was evaluated in studies of prophylactic efficacy using immunosuppressed mouse models of invasive candidiasis, aspergillosis, and pneumonia. Rezafungin reduction of CFU burden was generally greater with increasing drug concentrations (5, 10, or 20 mg/kg) and when rezafungin was administered closer to the time of fungal challenge (day -1, -3, or -5). Similarly, in the aspergillosis model, survival rates increased with drug concentrations and when rezafungin was administered closer to the time of fungal challenge. Against , rezafungin significantly reduced trophic nuclei and asci counts at all doses tested. Rezafungin prevented infection at the two higher doses compared to vehicle and had comparable activity to the active control trimethoprim-sulfamethoxazole at human equivalent doses for prevention. These findings support phase 3 development of rezafungin and the potential for single-agent prophylaxis against invasive fungal disease caused by spp., spp., and .