P-1195. Activity of manogepix against surveillance yeast isolates collected from the United States in 2023

TL;DR

Manogepix shows strong antifungal activity against various yeast species, including drug-resistant strains like C. auris, in a U.S. surveillance study.

Contribution

The study evaluates manogepix's in vitro efficacy against a diverse range of clinical yeast isolates in the U.S.

Findings

Manogepix had lower MIC50/90 values than other antifungals for most Candida species.

C. auris isolates showed high resistance to fluconazole but remained susceptible to manogepix.

Elevated MICs were observed for C. krusei and some Cryptococcus neoformans isolates.

Abstract

Manogepix (MGX) targets the fungal Gwt1 enzyme. Fosmanogepix, the prodrug of MGX is undergoing phase 3 clinical trials for treating invasive candidiasis and mould infections. Here, we assessed the in vitro activity of MGX against yeast isolates collected from patients with invasive infections.Tested yeast in United States manogepix surveillance program in 2023MIC50, MIC90, for manogepix and select comparators of organisms with more than 10 species tested1 Based on breakpoints from CLSI M27M44S 3rd Ed (2022)2 Based on CDC resistant-only breakpoints (https://www.cdc.gov/candida-auris/hcp/laboratories/antifungal-susceptibility-testing.html)

Tested yeast in United States manogepix surveillance program in 2023

MIC50, MIC90, for manogepix and select comparators of organisms with more than 10 species tested

1 Based on breakpoints from CLSI M27M44S 3rd Ed (2022)

2 Based on CDC resistant-only breakpoints (https://www.cdc.gov/candida-auris/hcp/laboratories/antifungal-susceptibility-testing.html)

A total of 298 yeast isolates were collected in 2023 from 24 hospitals in the United States (US). Isolates were tested by reference broth microdilution method according to CLSI guidelines against MGX, anidulafungin (AND) and fluconazole (FLC). Susceptible (S) or nonsusceptible (NS) isolates were interpreted by CLSI and CDC guidelines (resistant-only for C. auris). No breakpoints are available for MGX.

There were 19 different species of yeast represented (Figure 1). Candida glabrata was the most common organism (81/298, 27.2%), followed by C. albicans (66/298, 22.1%), C. parapsilosis (59/298, 19.8%), and C. tropicalis (25/298, 8.4%). There were 12 C. auris (4.0%). For non-Candida yeast, 3 different species were represented. MGX MIC50/90 values against Candida spp. were 0.015/0.06 mg/L (separated by species in Table 1). The MIC50/90 was lower for MGX than all other comparators. For C. albicans, 2 isolates were FLC-NS (one intermediate, I, one resistant, R) with MGX MICs of 0.008 mg/L; for the 1 isolate NS to AND, MGX MIC was 0.008 mg/L. Seven FLC-R and 3 AND-NS C. glabrata isolates exhibited MGX MICs ranging from 0.03 – 0.06 mg/L. MGX MICs ranged from 0.008 to 0.06 mg/L against C. auris; all isolates were FLC-R and 2 isolates were AND-R. Elevated MGX MICs (≥ 0.5 mg/L) were seen for C. krusei (9/9 isolates) and some Cryptococcus neoformans (2/7 isolates).

MGX has potent in vitro activity among diverse yeast species collected in a US-based surveillance program. For most species, MIC90 was ≤ 0.03 mg/L including organisms of critical concern like C. auris. Elevated MICs were seen with C. krusei and some Cryptococcus neoformans which has also been observed previously. These data indicate that MGX is a promising novel antifungal agent for the treatment of infections due to yeast.

Marisa Winkler, MD, PhD, Basilea: Advisor/Consultant|Basilea: Grant/Research Support|GSK: Advisor/Consultant|GSK: Grant/Research Support|Melinta Therapeutics: Advisor/Consultant|Melinta Therapeutics: Grant/Research Support|Mundipharma: Advisor/Consultant|Mundipharma: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pulmocide: Advisor/Consultant|Pulmocide: Grant/Research Support Mariana Castanheira, PhD, Melinta Therapeutics: Advisor/Consultant|Melinta Therapeutics: Grant/Research Support

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