Pharmacokinetics and Pharmacodynamics of Ibrexafungerp

McCarthy, Matthew W

doi:10.1007/s40268-021-00376-x

Cited by 19 publications

(22 citation statements)

References 46 publications

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“…Ibrexafungerp is a triterpenoid antifungal that produces fungicidal activity in Candida by inhibiting 1,3-β-D-glucan synthase, similarly to the mechanism of action of echinocandins. Unlike the echinocandins, ibrexafungerp is orally bioavailable, approximately 50% in animal studies, making it the only oral glucan synthase inhibitor [ 46 , 47 ].…”

Section: Ibrexafungerpmentioning

confidence: 99%

Antifungal Resistance and the Role of New Therapeutic Agents

Logan

Wolfe

Williamson

2022

Curr Infect Dis Rep

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Purpose of Review Advances in health care over time have led to an evolution in the epidemiology of invasive fungal infections. There is an increasing concern for antifungal resistance and emergence of less common fungal species for which optimal therapies are not well defined. The purpose of this review is to describe mechanisms of antifungal resistance and to evaluate the modern role of new and investigational antifungals. Recent Findings Isavuconazole and ibrexafungerp represent the two newest antifungal agents. Evidence from in vivo and in vitro studies has been published recently to help define their place in therapy and potential roles in treating resistant fungi. Isavuconazole is a broad-spectrum triazole antifungal with evidence to support its use in invasive aspergillosis and mucormycosis. Its utility in treating voriconazole-resistant Candida should be confirmed with susceptibility testing if available. Ibrexafungerp is an oral glucan synthase inhibitor with little cross-resistance among currently available antifungals, including echinocandins. It is a promising new agent for invasive candidiasis, including azole-resistant Candida species, and in combination therapy with voriconazole for aspergillosis. Multiple antifungals, some with novel mechanisms, are in development, including rezafungin, oteseconazole, olorofim, fosmanogepix, and opelconazole. Summary Both isavuconazole and ibrexafungerp are welcome additions to the arsenal of antifungals, and the prospect of more antifungal options in the future is encouraging. Such an array of antifungals will be important as antifungal resistance continues to expand alongside evolving medical practices. However, managing resistant fungal infections will grow in complexity as the unique role of each new agent is defined.

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Section: Ibrexafungerpmentioning

confidence: 99%

Antifungal Resistance and the Role of New Therapeutic Agents

Logan

Wolfe

Williamson

2022

Curr Infect Dis Rep

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“…Ibrexafungerp (previously MK-3118 and SCY-078; SCYNEXIS, Inc.; Jersey City, NJ, USA) disrupts fungal cell wall synthesis through the inhibition of (1,3)-β-D-glucan synthase [27]. Glucan synthase inhibition is also the mechanism of action of the echinocandins and has been demonstrated to result in a clinically meaningful effect in the treatment of yeast and mold infections.…”

Section: Ibrexafungerp Mechanism Of Actionmentioning

confidence: 99%

Ibrexafungerp, a Novel Triterpenoid Antifungal in Development for the Treatment of Mold Infections

Angulo

Alexander

Rautemaa‐Richardson

et al. 2022

JoF

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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 Aspergillus 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 Aspergillus 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.

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“…Among these, VT-1598 (Viamet Pharmaceuticals, Durham, NC) has a broad spectrum of activity including Histoplasma and was granted orphan drug designation for the treatment of coccidioidomycosis. Ibrexafungerp is an oral triterpenoid antifungal with a mechanism of action similar to echinocandins, inhibiting 1,3-β-D-glucan synthase [ 75 , 77 , 78 ]. It received FDA approval in 2021 for treatment of vulvovaginal candidiasis.…”

Section: Novel Fungal Therapies For Histoplasmosismentioning

confidence: 99%

“…An ongoing phase 3 multicenter, open-label study evaluating the efficacy and safety of ibrexafungerp in patients with fungal diseases refractory to or intolerant of standard treatment was expanded to include histoplasmosis (FURI, NCT03059992) [ 77 ]. Other novel agents with Histoplasma activity include olorofim, fosmanogepix, and nikkomycin Z [ 76 , 78 , 79 •, 80 – 83 ]. Both olorofim and fosmanogepix have activity against Histoplasma , are available in oral and intravenous formulations, and are actively being pursued for multiple fungal applications.…”

Section: Novel Fungal Therapies For Histoplasmosismentioning

confidence: 99%

Updates on Histoplasmosis in Solid Organ Transplantation

Saullo

Miller

2022

Curr Fungal Infect Rep

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Purpose of Review Histoplasmosis remains a challenging infection in solid organ transplantation. This review provides a topic update with emphasis on the changing Histoplasma epidemiology, along with new diagnostic and treatment innovations. Recent Findings Recent years have observed expanding Histoplasma geographic distribution due to climate change, environmental disruption, and host factors. Early clinical experience also suggests a relationship between COVID-19 infection and histoplasmosis, particularly among immunocompromised individuals. Advances in diagnostic methods, such as newer enzyme immunoassays and molecular techniques, have broadened the capability for expedient and highly specific pathogen identification. Novel drug innovations, including the development of new formulations of existing antifungal agents, extended-spectrum azoles and new antifungal drug classes have expanded therapeutic options. Summary Advances in organ transplantation have largely outpaced those for histoplasmosis. However, these emerging insights enhance our understanding of this pathogen and management of clinical infection, particularly for transplant recipients with a higher incidence and severity of disease.

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Pharmacokinetics and Pharmacodynamics of Ibrexafungerp

Cited by 19 publications

References 46 publications

Antifungal Resistance and the Role of New Therapeutic Agents

Antifungal Resistance and the Role of New Therapeutic Agents

Ibrexafungerp, a Novel Triterpenoid Antifungal in Development for the Treatment of Mold Infections

Updates on Histoplasmosis in Solid Organ Transplantation

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