Basilea Pharmaceutica has commenced its Phase 3 clinical trial, named Fosmanogepix Against Standard-of-care Treatment in Invasive Candidiasis (FAST-IC), to evaluate the efficacy and safety of fosmanogepix in adult patients with candidemia and invasive candidiasis. This study marks a significant step in addressing life-threatening fungal infections prevalent in hospitalized patients.
Fosmanogepix: A Novel Antifungal Approach
Fosmanogepix is a first-in-class antifungal with a novel mechanism of action. Available in both intravenous and oral formulations, it has undergone Phase 1 and Phase 2 evaluations, demonstrating potential in treating candidemia, including Candida auris, and invasive mold infections. The drug's active moiety, manogepix, inhibits the fungal enzyme Gwt1, which is essential for fungal cell wall integrity, adhesion, and pathogenicity. By targeting Gwt1, fosmanogepix disrupts the fungi's ability to evade host defenses.
FAST-IC Trial Design
The FAST-IC trial is a global, multi-center, randomized, active-controlled, double-blind Phase 3 study. It compares intravenous fosmanogepix to intravenous caspofungin, a standard-of-care antifungal, in adult patients with candidemia and/or invasive candidiasis. Approximately 450 patients will be enrolled and randomized in a 2:1 ratio to receive either fosmanogepix or caspofungin. The trial includes an optional oral switch to fosmanogepix or fluconazole in the respective treatment groups.
Clinical Need and Potential Impact
Invasive Candida infections are a major concern in hospitalized patients, often leading to high mortality rates. Candida species are a leading cause of bloodstream infections in US hospitals, with mortality rates as high as 40% even with antifungal therapy. Fosmanogepix offers a potential new treatment option in this high medical need area, especially given its activity against multi-drug-resistant strains.
Previous Studies
Previous Phase 2 data indicated that fosmanogepix was tolerated in patients with renal insufficiency and Candida spp. infections. In a small study, 12 of 14 patients with renal insufficiency completed the treatment regimen, with successful outcomes defined as survival and clearance of Candida from blood cultures without additional antifungal treatment.
Future Directions
Basilea is also planning a second Phase 3 study to investigate fosmanogepix in treating adult patients with invasive mold infections. This underscores the company's commitment to addressing severe fungal infections with innovative therapeutic options.
