Other Novel Antifungal Drugs in Ongoing Clinical Trials for Invasive Fungal Infections
| Antifungal Drug . | Type of Molecule and Mechanism of Action . | PK/PD Properties . | Antifungal Spectrum . | FDA Designation and Clinical Research Stagea . |
|---|---|---|---|---|
| Tetrazoles (VT-1161, VT-1129, and VT-1598) | Azoles; inhibition of ergosterol biosynthesis | Similar to azoles; decreased affinity for human P450 cytochrome enzymes (less toxicity and less drug-drug interactions) | Comparable to triazoles; active against Candida spp. including C. auris and some azole-resistant species;only VT-1598 active against Aspergillus spp. (except azole-resistant Cyp51A mutant strains); marginal activity against Mucorales (only Rhizopus arrhizus var. arrhizus) | VT-1161: QIDP, fast track; VT-1129: orphan drug, QIDP; VT-1598: orphan drug, QIDP, fast track; phase I (coccidioidomycosis; ongoing) |
| Encochleated amphotericin B | Polyenes; drug conditioned in a cochleate; targeted delivery to reticulo-endothelial cells | Similar to amphotericin B (less toxicity) | Comparable to amphotericin B | Orphan drug, QIDP, fast track; phase I (patients with HIV and prior cryptococcosis; completed) [83]; phase II (patients with HIV and cryptococcal meningitis; ongoing) |
| PC945 | Triazoles; inhibition of ergosterol biosynthesis | Similar to triazoles; inhaled route of administration | Comparable to other triazoles, but improved activity against azole-resistant Aspergillus fumigates | Phase I (healthy subjects and mild asthma; completed) [84]; phase II (preemptive treatment of IPA in lung transplant recipients; interrupted) |
| T-2307 | Arylamidine | Under investigation | Broad antifungal activity against Candida spp., Cryptococcus spp. and Aspergillus spp., including azole- and echinocandin-resistant strains | Phase I (ongoing) |
| Inhibition of mitochondrial respiratory chain complexes III and IV | ||||
| MGCD290 | Inhibitor of histone deacetylase | Under investigation | Modest antifungal activity per se; synergism with azoles against Candida spp., Cryptococcus spp., Aspergillus spp., Mucorales, Fusarium spp. and Scedosporium spp. | None |
| Antifungal Drug . | Type of Molecule and Mechanism of Action . | PK/PD Properties . | Antifungal Spectrum . | FDA Designation and Clinical Research Stagea . |
|---|---|---|---|---|
| Tetrazoles (VT-1161, VT-1129, and VT-1598) | Azoles; inhibition of ergosterol biosynthesis | Similar to azoles; decreased affinity for human P450 cytochrome enzymes (less toxicity and less drug-drug interactions) | Comparable to triazoles; active against Candida spp. including C. auris and some azole-resistant species;only VT-1598 active against Aspergillus spp. (except azole-resistant Cyp51A mutant strains); marginal activity against Mucorales (only Rhizopus arrhizus var. arrhizus) | VT-1161: QIDP, fast track; VT-1129: orphan drug, QIDP; VT-1598: orphan drug, QIDP, fast track; phase I (coccidioidomycosis; ongoing) |
| Encochleated amphotericin B | Polyenes; drug conditioned in a cochleate; targeted delivery to reticulo-endothelial cells | Similar to amphotericin B (less toxicity) | Comparable to amphotericin B | Orphan drug, QIDP, fast track; phase I (patients with HIV and prior cryptococcosis; completed) [83]; phase II (patients with HIV and cryptococcal meningitis; ongoing) |
| PC945 | Triazoles; inhibition of ergosterol biosynthesis | Similar to triazoles; inhaled route of administration | Comparable to other triazoles, but improved activity against azole-resistant Aspergillus fumigates | Phase I (healthy subjects and mild asthma; completed) [84]; phase II (preemptive treatment of IPA in lung transplant recipients; interrupted) |
| T-2307 | Arylamidine | Under investigation | Broad antifungal activity against Candida spp., Cryptococcus spp. and Aspergillus spp., including azole- and echinocandin-resistant strains | Phase I (ongoing) |
| Inhibition of mitochondrial respiratory chain complexes III and IV | ||||
| MGCD290 | Inhibitor of histone deacetylase | Under investigation | Modest antifungal activity per se; synergism with azoles against Candida spp., Cryptococcus spp., Aspergillus spp., Mucorales, Fusarium spp. and Scedosporium spp. | None |
Abbreviations: FDA, Food and Drug Administration; HIV, human immunodeficiency virus; IPA, invasive pulmonary infection; PK/PD, pharmacokinetic-pharmacodynamic; QIDP, qualified infectious disease product designation.
Only studies related to invasive fungal infections are mentioned. Phase II or III trials for localized fungal diseases (eg, vulvovaginal candidiasis and onychomycosis) or chronic pulmonary aspergillosis are not included.
Other Novel Antifungal Drugs in Ongoing Clinical Trials for Invasive Fungal Infections
| Antifungal Drug . | Type of Molecule and Mechanism of Action . | PK/PD Properties . | Antifungal Spectrum . | FDA Designation and Clinical Research Stagea . |
|---|---|---|---|---|
| Tetrazoles (VT-1161, VT-1129, and VT-1598) | Azoles; inhibition of ergosterol biosynthesis | Similar to azoles; decreased affinity for human P450 cytochrome enzymes (less toxicity and less drug-drug interactions) | Comparable to triazoles; active against Candida spp. including C. auris and some azole-resistant species;only VT-1598 active against Aspergillus spp. (except azole-resistant Cyp51A mutant strains); marginal activity against Mucorales (only Rhizopus arrhizus var. arrhizus) | VT-1161: QIDP, fast track; VT-1129: orphan drug, QIDP; VT-1598: orphan drug, QIDP, fast track; phase I (coccidioidomycosis; ongoing) |
| Encochleated amphotericin B | Polyenes; drug conditioned in a cochleate; targeted delivery to reticulo-endothelial cells | Similar to amphotericin B (less toxicity) | Comparable to amphotericin B | Orphan drug, QIDP, fast track; phase I (patients with HIV and prior cryptococcosis; completed) [83]; phase II (patients with HIV and cryptococcal meningitis; ongoing) |
| PC945 | Triazoles; inhibition of ergosterol biosynthesis | Similar to triazoles; inhaled route of administration | Comparable to other triazoles, but improved activity against azole-resistant Aspergillus fumigates | Phase I (healthy subjects and mild asthma; completed) [84]; phase II (preemptive treatment of IPA in lung transplant recipients; interrupted) |
| T-2307 | Arylamidine | Under investigation | Broad antifungal activity against Candida spp., Cryptococcus spp. and Aspergillus spp., including azole- and echinocandin-resistant strains | Phase I (ongoing) |
| Inhibition of mitochondrial respiratory chain complexes III and IV | ||||
| MGCD290 | Inhibitor of histone deacetylase | Under investigation | Modest antifungal activity per se; synergism with azoles against Candida spp., Cryptococcus spp., Aspergillus spp., Mucorales, Fusarium spp. and Scedosporium spp. | None |
| Antifungal Drug . | Type of Molecule and Mechanism of Action . | PK/PD Properties . | Antifungal Spectrum . | FDA Designation and Clinical Research Stagea . |
|---|---|---|---|---|
| Tetrazoles (VT-1161, VT-1129, and VT-1598) | Azoles; inhibition of ergosterol biosynthesis | Similar to azoles; decreased affinity for human P450 cytochrome enzymes (less toxicity and less drug-drug interactions) | Comparable to triazoles; active against Candida spp. including C. auris and some azole-resistant species;only VT-1598 active against Aspergillus spp. (except azole-resistant Cyp51A mutant strains); marginal activity against Mucorales (only Rhizopus arrhizus var. arrhizus) | VT-1161: QIDP, fast track; VT-1129: orphan drug, QIDP; VT-1598: orphan drug, QIDP, fast track; phase I (coccidioidomycosis; ongoing) |
| Encochleated amphotericin B | Polyenes; drug conditioned in a cochleate; targeted delivery to reticulo-endothelial cells | Similar to amphotericin B (less toxicity) | Comparable to amphotericin B | Orphan drug, QIDP, fast track; phase I (patients with HIV and prior cryptococcosis; completed) [83]; phase II (patients with HIV and cryptococcal meningitis; ongoing) |
| PC945 | Triazoles; inhibition of ergosterol biosynthesis | Similar to triazoles; inhaled route of administration | Comparable to other triazoles, but improved activity against azole-resistant Aspergillus fumigates | Phase I (healthy subjects and mild asthma; completed) [84]; phase II (preemptive treatment of IPA in lung transplant recipients; interrupted) |
| T-2307 | Arylamidine | Under investigation | Broad antifungal activity against Candida spp., Cryptococcus spp. and Aspergillus spp., including azole- and echinocandin-resistant strains | Phase I (ongoing) |
| Inhibition of mitochondrial respiratory chain complexes III and IV | ||||
| MGCD290 | Inhibitor of histone deacetylase | Under investigation | Modest antifungal activity per se; synergism with azoles against Candida spp., Cryptococcus spp., Aspergillus spp., Mucorales, Fusarium spp. and Scedosporium spp. | None |
Abbreviations: FDA, Food and Drug Administration; HIV, human immunodeficiency virus; IPA, invasive pulmonary infection; PK/PD, pharmacokinetic-pharmacodynamic; QIDP, qualified infectious disease product designation.
Only studies related to invasive fungal infections are mentioned. Phase II or III trials for localized fungal diseases (eg, vulvovaginal candidiasis and onychomycosis) or chronic pulmonary aspergillosis are not included.
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