New Perspectives on Antimicrobial Agents: Fosmanogepix

Invasive fungal infections (IFIs) are associated with high mortality rates and pose important therapeutic challenges because of the limited number of antifungal drug classes, their toxicity, and the emergence of resistance. Novel first-in-class antifungal agents have been recently approved (ibrexafungerp) or are currently being tested in clinical trials and are available via expanded access programs (olorofim, fosmanogepix). Among them, fosmanogepix (a prodrug of manogepix) represents a promising future therapeutic option for many IFIs because of its broad-spectrum antifungal activity and its favorable pharmacologic properties, such as oral bioavailability, extended tissue distribution (including the central nervous system), a good safety profile, and the absence of relevant drug-drug interactions. Fosmanogepix may become an interesting alternative option for the treatment of invasive candidiasis due to multidrug-resistant isolates (e.g., Candidozyma auris) or invasive aspergillosis due to azole-resistant Aspergillus spp. It also demonstrated very encouraging results for the treatment of invasive fusariosis and other refractory mold infections (e.g., scedosporiosis, lomentosporiosis). Novel gepix compounds have been developed and could make their niche in the future (e.g., APX2039, prodrug: APX2096, for cryptococcal meningitis, and APX2020, prodrug: APX2097, for coccidioidomycosis). This review discusses the future place of fosmanogepix in the antifungal armamentarium against IFIs.