Table 1.
Investigational antifungals currently involved with active preparations for clinical trials
| Agent | Class | Mechanism of action | Formulation | Spectrum of activity including resistant fungi | FDA designations | Phase II and III clinical trials |
|---|---|---|---|---|---|---|
| Ibrexafungerp | Terpenoid | Inhibition of (1,3) β-d-glucan synthase |
Oral Intravenous |
MDR Candida spp. MDR Aspergillus spp. |
QIDP |
˖ Oral step-down in IC ˖ Acute and Recurrent VVC ˖ Invasive C. auris infections ˖ IPA in combination with voriconazole ˖ IFI refractory to standard therapies |
| Rezafungin | Echinocandin | Inhibition of (1,3) β-d-glucan synthase | Intravenous | Like other echinocandins |
QIDP Fast track |
˖ IC ˖ Prophylaxis of IFI in stem-cell transplants |
| Oteseconazole (VT-1161) | Tetrazole | Lanosterol 14⍺-demethylase inhibitor |
Oral Intravenous |
Echinocandin-resistant C. glabrata Rhizopus spp. Trichophyton spp. Coccidioides spp. |
QIDP Fast track |
˖ Acute and recurrent VVC ˖ Moderate-to-severe onychomycosis |
| VT-1129 | Tetrazole | Lanosterol 14⍺-demethylase Inhibitor |
Oral Intravenous |
Cryptococcus spp. C. glabrata, C. krusei |
Orphan drug QIDP |
˖ Cryptococcosis |
| VT-1598 | Tetrazole | Lanosterol 14⍺-demethylase Inhibitor |
Oral Intravenous |
Resistant Candida spp., C. auris Cryptococcus spp. Endemic fungi |
Orphan drug QIDP Fast track |
˖ Phase I trials targeting trials for C. auris, Cryptococcus, and Coccidioides infections |
| Fosmanogepix | Gwt1 inhibitor | Inhibits the formation of mannoproteins in cell wall and exposing (1,3) β-d-glucan to the host immune system. |
Oral Intravenous |
MDR Candida spp. C. auris Scedosporium spp., Fusarium spp., Mucorales spp. |
Orphan drug QIDP Fast track |
˖ IC in non-neutropenic patients ˖ Invasive C. auris infections ˖ IFI due to Aspergillus or rare molds |
| Olorofim | Orotomide | Inhibits dihydroorotate dehydrogenase blocking pyrimidine biosynthesis |
Oral Intravenous |
MDR Aspergillus spp. Lomentospora spp., Scedosporium spp. Endemic fungi |
Orphan drug | ˖ Refractory of resistant IFIs |
| ATI-2307 | Arylamidine | Inhibits fungal mitochondrial synthesis | MDR Candida spp., C. auris, Cryptococcus spp. | ˖ Phase I trials targeting future trials for cryptococcosis and MDR IC | ||
| CAmB | Polyene | Spiraled lipid bilayer encasing amphotericin B | Oral | Like amphotericin B |
Orphan drug QIDP Fast track |
˖ Refractory mucocutaneous candidiasis ˖ Moderate-to-severe VVC ˖ Cryptococcal meningitis |
| PC945 | Triazole | Lanosterol 14⍺-demethylase Inhibitor | Inhalation | Triazole-resistant A. fumigatus, C. auris |
˖ IPA in lung transplants and chronic lung disease ˖ In combination with triazole for IPA |
Abbreviations: Encochleated amphotericin B (CAmB), central nervous system (CNS), invasive candidiasis (IC), invasive fungal infection (IFI), invasive pulmonary aspergillosis (IPA), multidrug-resistant (MDR), vulvovaginal candidiasis (VVC)