Switzerland-based Basilea Pharmaceutica announced in recent weeks that it had begun its Fosmanogepix Against Standard-of-care Treatment in Invasive Candidiasis (FAST-IC) phase 3 study. This study evaluates the efficacy and safety of the broad-spectrum antifungal fosmanogepix for the treatment of adult patients with candidemia and/or invasive candidiasis, that is Candida yeast bloodstream or deep-seated tissue infections.1
“We are very pleased to have activated the first study center in the phase 3 program for fosmanogepix and look forward to enrolling patients into FAST-IC,” Basilea Chief Medical Officer Marc Engelhardt, MD, said in a statement. “Invasive Candida infections are life-threatening complications for many hospitalized patients and associated with high mortality, and fosmanogepix offers a potential new treatment option in this high medical need area.1
Fosmanogepix is a first-in-class antifungal investigational therapy with a novel mechanism of action. It is available in intravenous and oral formulations and has been evaluated for efficacy and safety in a phase 1 / phase 2 program, including 3 open-label phase 2 studies for the treatment of Candidemia, including Candida auris, and invasive mold infections.1
The therapy’s mechanism of action involves the inhibition of the fungal enzyme Gwt1 by the active moiety, manogepix. The manufacturer indicates that Gwt1 is highly conserved across fungal strains and is essential for trafficking and anchoring manoprotein to the outer cell wall in fungi; with mannoproteins integral to fungal cell wall integrity, adhesion, pathogenicity, and for evading host defenses.2
Study Parameters
FAST-IC is a global, multi-center, randomized, active-controlled, double-blind phase 3 study and investigates intravenous (IV) fosmanogepix versus a standard-of-care regimen of IV caspofungin in adult patients with candidemia and/or invasive candidiasis. The study is expected to enroll approximately 450 patients, who will be randomized in a 2:1 ratio to either fosmanogepix or caspofungin.1
There is an optional oral switch to fosmanogepix in the fosmanogepix group and to fluconazole in the caspofungin group. The Swiss-based global company PSI CRO AG will manage the phase 3 program.1
What You Need to Know
Basilea Pharmaceutica has initiated a phase 3 clinical trial (FAST-IC) to evaluate the efficacy and safety of fosmanogepix, a broad-spectrum antifungal, for treating adult patients with candidemia and invasive candidiasis.
Fosmanogepix works by inhibiting the fungal enzyme Gwt1, which is vital for maintaining fungal cell wall integrity and evading host defenses. This novel mechanism makes it a first-in-class antifungal therapy with both intravenous and oral formulations.
The FAST-IC trial is a double-blind, randomized, and global study comparing fosmanogepix with caspofungin, a standard antifungal treatment. The study aims to enroll 450 patients, with plans for future research on fosmanogepix for invasive mold infections.
In previous reporting by Contagion, phase 2 data was shared in patients who had Candida spp renal insufficiency. Inclusion for participants was a positive blood culture for Candida spp within 96 hours prior to study entry, and they did not receive antifungal treatment within the previous 2 days. Patients with neutropenia, C krusei infection, deep-seated Candida infections, or those on hemodialysis were excluded.2
Study participants received fosmanogepix for up to 14 days, as 1000mg intravenously (IV) twice daily for 1 day, then 600mg IV daily for at least 2 days, followed by either 600mg IV or 700mg orally daily. Fluconazole was to be administered to any participants who required antifungal treatment beyond the 14 day regimen with fosmanogepix.2
Within this small study, 12 of the 14 (85%) with renal insufficiency completed the treatment, and treatment was successful for each of the 12 participants at the end of the regimen. A successful outcome was defined as survival with clearance of Candida from blood cultures with no additional antifungal treatment.2
In concurrence with the company’s latest trial, Basilea is planning another study with the therapy. “We are working towards starting the second phase 3 study investigating fosmanogepix in the treatment of adult patients with invasive mold infections around year-end,” Engelhardt said.1
References
1. Basilea initiates clinical phase 3 study with antifungal fosmanogepix in candidemia and invasive candidiasis. Basilea press release. September 24, 2024. Accessed October 7, 2024.
https://www.basilea.com/news#news_1516
2.Bender K. Investigational Antifungal Tolerated in Patients with Renal Insufficiency. Contagion. November 4, 2020. Accessed October 7, 2024.
https://www.contagionlive.com/view/investigational-antifungal-tolerated-in-patients-with-renal-insufficiency
