Review of the Novel Echinocandin Antifungal Rezafungin: Animal Studies and Clinical Data.

Yanan Zhao,David S Perlin

doi:10.3390/jof6040192

Abstract

Rezafungin is a novel echinocandin drug being developed as a first-line option for treatment and prevention of invasive fungal infections. As a result of a structural modification in its parent molecule anidulafungin, rezafungin has acquired unique chemical stability conferring prolonged pharmacokinetics, as well as an administration advantage in the clinical setting compared to other drugs in the same class. Rezafungin displays potent in vitro activity against a wide spectrum of fungal pathogens, which is reflected in robust in vivo efficacy and/or pharmacodynamic studies using various animal models as well as in promising clinical trials data. This review describes in vivo characterization of rezafungin using animal models, current status of clinical development and key findings from these studies.

Highlights

Echinocandin class antifungals disrupt fungal cells via inhibition of the biosynthesis of β-1,3-D-glucan, an essential component of the fungal cell wall [1]
This review will discuss the in vivo efficacy and pharmacokinetics and pharmacodynamics (PK/PD) of rezafungin in animal models, and clinical evidence acquired from the completed clinical trials far
These efficacy results were echoed by the second study, in which four C. auris strains with rezafungin minimum inhibitory concentration (MIC) ranging from 0.06 to 2 μg/mL were included in the evaluation [16]

Summary

Introduction

Echinocandin class antifungals disrupt fungal cells via inhibition of the biosynthesis of β-1,3-D-glucan, an essential component of the fungal cell wall [1]. Its chemical structure is slightly modified from anidulafungin (Figure 1), in which the hemiaminal region at the C5 ornithine position is replaced with a choline aminal ether [6] This slight structural modification has conferred to rezafungin an exceptional stability and enhanced solubility, which account for its largely prolonged pharmacokinetic (PK) property compared to other drugs in this class [7,8,9]. From a clinical practice standpoint, a direct benefit of the long-acting feature of rezafungin is less frequent dosing (e.g., once weekly) when compared to the daily dosing requirement for other echinocandin drugs This dosing strategy has the potential to increase patient compliance, especially for those who require longer course of therapy after hospital discharge.

Preclinical

Animal Models

In Vivo Efficacy against Other Fungal Pathogens

Objective

Findings

Conclusions