Clinical Efficacy and Safety of a Novel Antifungal, Fosmanogepix, in Patients with Candidemia Caused by Candida auris : Results from a Phase 2 Trial

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 .

Pharmacokinetics, safety, and tolerability of fosmanogepix IV to oral switch and multiple IV doses in healthy participants

“…FMGX was rapidly converted to MGX after IV administration (Table S2), similar to observations from previous PK evaluations of FMGX with measurable FMGX concentrations available for only 4–24 h after IV infusions on days 1–7 ( 12 ). Geometric mean plasma concentrations of MGX on day 1 were highest for cohort A, with a loading regimen of 1,500 mg/3 h BID (9 h apart).…”

“…One event each of AST and ALT elevation occurred while participants were taking FMGX at home; neither was considered to be clinically significant. These findings support the duration and provide a detailed PK profile of the treatment regimen assessed in the phase 2 efficacy and safety studies of FMGX for the treatment of candidemia and/or invasive candidiasis caused by Candida auris (NCT04148287) ( 12 ) and invasive aspergillosis and other rare molds (NCT04240886) ( 6 , 13 , 14 ).…”

“…A comparable IV PK profile with drug exposures maintained after switching to oral dosing allows an opportunity to use PO formulations in outpatient clinical settings that require prolonged FMGX treatment. FMGX has also been evaluated in phase 2 studies for up to 14 days in non-neutropenic patients with candidemia (NCT03604705: IV 1,000 mg BID on day 1 followed by IV 600 mg and an optional switch to PO 700 mg) ( 18 , 19 ) and for up to 42 days in patients with infections caused by Candida auris , Aspergillus spp., and other rare molds [NCT04240886 ( 14 ) and NCT04148287 ( 12 ): FMGX IV loading dose of 1,000 mg BID on day 1 followed by IV 600 mg and PO switch to 800 mg) ( 6 , 13 , 20 ) with encouraging results ( 21 ). IV loading dose (1,000 mg twice on day 1) with IV (600 mg QD) or oral (800 mg QD) maintenance doses are planned for evaluation in phase 3 trials ( 22 ).…”

In vitro activity of manogepix and comparators against infrequently encountered yeast and mold isolates from the SENTRY Surveillance Program (2017–2022)

“…The first (NCT03604705; clinicaltrials.gov ) was an open-label, non-comparative study assessing the safety and efficacy of fosmanogepix in the treatment of non-neutropenic patients with candidemia which met its primary efficacy endpoint with a treatment success rate of 80% with an acceptable safety profile ( 54 ). The second study (NCT04148287; clinicaltrials.gov ) tested the safety and efficacy of fosmanogepix treatment in patients with candidemia caused by C. auris ( 55 ). Treatment success at the end of study treatment and day 30 survival were 89% with no treatment-related adverse events or study drug discontinuations reported.…”

Phase 1b safety and pharmacokinetics of intravenous and oral fosmanogepix in patients with acute myeloid leukaemia and neutropenia

“…Initial results from completed Phase 1 and 2 clinical trials are in line with published preclinical and in vitro susceptibility data and animal models of infection. 18–21 The overall goals for the clinical development programme are to determine if fosmanogepix is a safe and effective treatment option for IFDs caused by the major pathogenic fungi (i.e. Candida , Cryptococcus and Aspergillus spp.)…”