SCY-078, a Novel Oral Glucan Synthase Inhibitor, for the Treatment of Invasive Aspergillosis: Evaluation of Antifungal Activity Singly and in Combination [PublishAheadOfPrint]

Invasive aspergillosis remains a major cause of death among the immunocompromised population and those receiving long-term immunosuppressive therapy. In light of increased azole resistance, variable outcomes with existing echinocandin mono and combination therapy, and persistent high mortality rates, new antifungal agents for the treatment of invasive aspergillosis are clearly needed.

SCY-078 is the first in class triterpenoid antifungal, a novel class of glucan synthase inhibitors, with broad in vitro and in vivo activity against a broad spectrum of Candida and Aspergillus. In vitro testing of clinical strains of Aspergillus fumigatus and non-fumigatus strains showed potent fungistatic activity of SCY-078 (minimum effective concentration, MEC₉₀ = 0.125 μg/ml) as compared with amphotericin B (MIC₉₀ = 8 μg/ml) and voriconazole (MIC₉₀ = 2 μg/ml). Combination testing of SCY-078 with isavuconazole or voriconazole demonstrated synergistic activity against the majority of the azole-susceptible strains tested, and SCY-078 in combination with amphotericin B was synergistic against the azole-susceptible strains, as well as one known resistant cyp51A mutant. SCY-078 may be an important additional antifungal for first-line or salvage mono or combination treatment of invasive aspergillosis.

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