Clinical efficacy and safety of a novel antifungal, Fosmanogepix, in patients with candidemia caused by Candida auris : results from a Phase 2 trial

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Authors

Vazquez, Jose A.
Pappas, Peter G.
Boffard, Kenneth D.
Paruk, Fathima
Bien, Paul A.
Tawadrous, Margaret
Ople, Eric
Wedel, Pamela
Oborska, Iwona
Hodges, Michael R.

Journal Title

Journal ISSN

Volume Title

Publisher

American Society for Microbiology

Abstract

Fosmanogepix (FMGX), a novel antifungal available in intravenous (IV) and oral formulations, has broad-spectrum activity against pathogenic yeasts and molds, including fungi resistant to standard of care antifungals. This multicenter, open-label, single-arm study evaluated FMGX safety and efficacy for treatment of candidemia and/or invasive candidiasis caused by Candida auris. Eligible participants were ≥18 years, with established candidemia and/or invasive candidiasis caused by C. auris, (cultured within 120 h [for candidemia] or 168 h [for invasive candidiasis without candidemia] with accompanying clinical signs) and limited treatment options. Participants were treated with FMGX (≤42 days; loading dose: 1000 mg IV twice daily [Day 1], followed by 600 mg IV once daily [QD]). Switching to oral FMGX 800 mg QD was permitted from Day 4. Primary endpoint was treatment success (survival and clearance of C. auris from blood/tissue cultures without additional antifungals) at the end of the study treatment (EOST), assessed by an independent data review committee (DRC). Day 30 survival was a secondary endpoint. In vitro susceptibility of Candida isolates was assessed. Nine participants with candidemia (male:6, female:3; 21 to 76 years) in intensive care units in South Africa were enrolled; all received IV FMGX only. DRC-assessed treatment success at EOST and Day 30 survival were 89% (8/9). No treatment related adverse events or study drug discontinuations were reported. FMGX demonstrated potent in vitro activity against all C. auris isolates (MIC range: 0.008 to 0.015 μg/mL [CLSI]; 0.004–0.03 μg/mL [EUCAST]), with the lowest MICs compared to other antifungals tested. Thus, the results showed that FMGX was safe, well-tolerated, and efficacious in participants with candidemia caused by C. auris.

Description

DATA AVAILABILITY: Upon request, and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions and exceptions, Pfizer may also provide access to the related individual de-identified participant data. See https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information.

Keywords

APX001, Candida auris, Gwt1 inhibitor, Candidemia, Fosmanogepix, Intensive care unit (ICU), Fosmanogepix (FMGX), SDG-03: Good health and well-being

Sustainable Development Goals

Citation

Vazquez, J.A., Pappas, P.G., Boffard, K., Paruk, F., Bien, P.A., Tawadrous, M., Ople, E., Wedel, P., Oborska, I., Hodges, M.R. et al. 'Clinical Efficacy and Safety of a Novel Antifungal, Fosmanogepix, in Patients with Candidemia Caused by Candida auris: Results from a Phase 2 Trial', Antimicrobial Agents and Chemotherapy, vol. 67, art. e0141922, doi : 10.1128/aac.01419-22.