Ibrexafungerp, a Novel Triterpenoid Antifungal in Development for the Treatment of Mold Infections
Molds are ubiquitous in the environment, and immunocompromised patients are at substantial risk of morbidity and mortality due to their underlying disease and the resistance of pathogenic molds to currently recommended antifungal therapies. This combination of weakened-host defense, with limited ant...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Journal of Fungi |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2309-608X/8/11/1121 |
| _version_ | 1797467643632943104 |
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| author | David A. Angulo Barbara Alexander Riina Rautemaa-Richardson Ana Alastruey-Izquierdo Martin Hoenigl Ashraf S. Ibrahim Mahmoud A. Ghannoum Thomas R. King Nkechi E. Azie Thomas J. Walsh |
| author_facet | David A. Angulo Barbara Alexander Riina Rautemaa-Richardson Ana Alastruey-Izquierdo Martin Hoenigl Ashraf S. Ibrahim Mahmoud A. Ghannoum Thomas R. King Nkechi E. Azie Thomas J. Walsh |
| author_sort | David A. Angulo |
| collection | DOAJ |
| description | Molds are ubiquitous in the environment, and immunocompromised patients are at substantial risk of morbidity and mortality due to their underlying disease and the resistance of pathogenic molds to currently recommended antifungal therapies. This combination of weakened-host defense, with limited antifungal treatment options, and the opportunism of environmental molds renders patients at risk and especially vulnerable to invasive mold infections such as <i>Aspergillus</i> and members of the Order Mucorales. Currently, available antifungal drugs such as azoles and echinocandins, as well as combinations of the same, offer some degree of efficacy in the prevention and treatment of invasive mold infections, but their use is often limited by drug resistance mechanisms, toxicity, drug-drug interactions, and the relative paucity of oral treatment options. Clearly, there is a need for agents that are of a new class that provides adequate tissue penetration, can be administered orally, and have broad-spectrum efficacy against fungal infections, including those caused by invasive mold organisms. Ibrexafungerp, an orally bioavailable glucan synthase inhibitor, is the first in a new class of triterpenoid antifungals and shares a similar target to the well-established echinocandins. Ibrexafungerp has a very favorable pharmacokinetic profile for the treatment of fungal infections with excellent tissue penetration in organs targeted by molds, such as the lungs, liver, and skin. Ibrexafungerp has demonstrated in vitro activity against <i>Aspergillus</i> spp. as well as efficacy in animal models of invasive aspergillosis and mucormycosis. Furthermore, ibrexafungerp is approved for use in the USA for the treatment of women with vulvovaginal candidiasis. Ibrexafungerp is currently being evaluated in clinical trials as monotherapy or in combination with other antifungals for treating invasive fungal infections caused by yeasts and molds. Thus, ibrexafungerp offers promise as a new addition to the clinician’s armamentarium against these difficult-to-treat infections. |
| first_indexed | 2024-03-09T18:56:35Z |
| format | Article |
| id | doaj.art-4d27cff5ce934122b26cb8c15cddd2e6 |
| institution | Directory Open Access Journal |
| issn | 2309-608X |
| language | English |
| last_indexed | 2024-03-09T18:56:35Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Fungi |
| spelling | doaj.art-4d27cff5ce934122b26cb8c15cddd2e62023-11-24T05:23:34ZengMDPI AGJournal of Fungi2309-608X2022-10-01811112110.3390/jof8111121Ibrexafungerp, a Novel Triterpenoid Antifungal in Development for the Treatment of Mold InfectionsDavid A. Angulo0Barbara Alexander1Riina Rautemaa-Richardson2Ana Alastruey-Izquierdo3Martin Hoenigl4Ashraf S. Ibrahim5Mahmoud A. Ghannoum6Thomas R. King7Nkechi E. Azie8Thomas J. Walsh9SCYNEXIS, Inc., Jersey City, NJ 07302, USADepartment of Medicine, Division of Infectious Diseases, Duke University School of Medicine, Durham, NC 27710, USAMycology Reference Centre Manchester, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester M23 9LT, UKMycology Reference Laboratory, National Center for Microbiology, Instituto de Salud Carlos III, 28029 Madrid, SpainDivision of Infectious Diseases, Medical University of Graz, 8036 Graz, AustriaDavid Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USADepartment of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USASCYNEXIS, Inc., Jersey City, NJ 07302, USASCYNEXIS, Inc., Jersey City, NJ 07302, USACenter for Innovative Therapeutics and Diagnostics, Richmond, VA 23223, USAMolds are ubiquitous in the environment, and immunocompromised patients are at substantial risk of morbidity and mortality due to their underlying disease and the resistance of pathogenic molds to currently recommended antifungal therapies. This combination of weakened-host defense, with limited antifungal treatment options, and the opportunism of environmental molds renders patients at risk and especially vulnerable to invasive mold infections such as <i>Aspergillus</i> and members of the Order Mucorales. Currently, available antifungal drugs such as azoles and echinocandins, as well as combinations of the same, offer some degree of efficacy in the prevention and treatment of invasive mold infections, but their use is often limited by drug resistance mechanisms, toxicity, drug-drug interactions, and the relative paucity of oral treatment options. Clearly, there is a need for agents that are of a new class that provides adequate tissue penetration, can be administered orally, and have broad-spectrum efficacy against fungal infections, including those caused by invasive mold organisms. Ibrexafungerp, an orally bioavailable glucan synthase inhibitor, is the first in a new class of triterpenoid antifungals and shares a similar target to the well-established echinocandins. Ibrexafungerp has a very favorable pharmacokinetic profile for the treatment of fungal infections with excellent tissue penetration in organs targeted by molds, such as the lungs, liver, and skin. Ibrexafungerp has demonstrated in vitro activity against <i>Aspergillus</i> spp. as well as efficacy in animal models of invasive aspergillosis and mucormycosis. Furthermore, ibrexafungerp is approved for use in the USA for the treatment of women with vulvovaginal candidiasis. Ibrexafungerp is currently being evaluated in clinical trials as monotherapy or in combination with other antifungals for treating invasive fungal infections caused by yeasts and molds. Thus, ibrexafungerp offers promise as a new addition to the clinician’s armamentarium against these difficult-to-treat infections.https://www.mdpi.com/2309-608X/8/11/1121new antifungal agentsibrexafungerpmoldstriterpenoidinvasive fungal infection |
| spellingShingle | David A. Angulo Barbara Alexander Riina Rautemaa-Richardson Ana Alastruey-Izquierdo Martin Hoenigl Ashraf S. Ibrahim Mahmoud A. Ghannoum Thomas R. King Nkechi E. Azie Thomas J. Walsh Ibrexafungerp, a Novel Triterpenoid Antifungal in Development for the Treatment of Mold Infections Journal of Fungi new antifungal agents ibrexafungerp molds triterpenoid invasive fungal infection |
| title | Ibrexafungerp, a Novel Triterpenoid Antifungal in Development for the Treatment of Mold Infections |
| title_full | Ibrexafungerp, a Novel Triterpenoid Antifungal in Development for the Treatment of Mold Infections |
| title_fullStr | Ibrexafungerp, a Novel Triterpenoid Antifungal in Development for the Treatment of Mold Infections |
| title_full_unstemmed | Ibrexafungerp, a Novel Triterpenoid Antifungal in Development for the Treatment of Mold Infections |
| title_short | Ibrexafungerp, a Novel Triterpenoid Antifungal in Development for the Treatment of Mold Infections |
| title_sort | ibrexafungerp a novel triterpenoid antifungal in development for the treatment of mold infections |
| topic | new antifungal agents ibrexafungerp molds triterpenoid invasive fungal infection |
| url | https://www.mdpi.com/2309-608X/8/11/1121 |
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