Activity of a Novel 1,3-Beta-
            <scp>d</scp>
            -Glucan Synthase Inhibitor, Ibrexafungerp (Formerly SCY-078), against
            <i>Candida glabrata</i>

Ghannoum, Mahmoud A.; Long, Lisa; Isham, N.; Hager, Christopher; Wilson, Rachel; Borroto–Esoda, Katyna; Barat, Stephen; Angulo, David

doi:10.1128/aac.01510-19

Cited by 29 publications

(20 citation statements)

References 8 publications

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“…Potent fungicidal activity has been demonstrated with ibrexafungerp in various Candida spp [27,34,37,49]. In a timekill study, ibrexafungerp demonstrated fungicidal activity (≥3-log reduction in cfu/mL) at 24 hours.…”

Section: Microbiologymentioning

confidence: 98%

“…However, ibrexafungerp, the first representative of the 'fungerp' family of compounds, is a structurally distinct triterpenoid glucan synthase inhibitor as compared to echinocandins and interacts differently with the target cell ( Figure 1) [25]. Thus, ibrexafungerp demonstrates in vitro activity against a broad range of Candida isolates with fks1 and fks2 point mutations that cause echinocandin resistance among C. glabrata, C. auris, and Aspergillus spp [26][27][28][29][30][31][32][33][34][35].…”

Section: Ibrexafungerpmentioning

confidence: 99%

“…is consistently greater than fluconazole, especially among echinocandin-and azole-resistant isolates [34,52]. A growing rate of resistance in C. glabrata isolates to azoles and echinocandins has been reported together with increased rate of treatment failures [27]. The MIC range for ibrexafungerp against wild-type and echinocandin-resistant strains was 1 to 2 μg/mL [32].…”

Section: Microbiologymentioning

confidence: 99%

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Oral Ibrexafungerp: an investigational agent for the treatment of vulvovaginal candidiasis

Azie¹,

Angulo²,

Dehn

et al. 2020

Expert Opinion on Investigational Drugs

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Introduction: Vulvovaginal candidiasis (VVC) is a common fungal infection caused by predominantly Candida albicans, and is diagnosed in up to 40% of women with vaginal complaints in the primary care setting. Approximately 75% of women experience at least one episode during their reproductive years. Areas covered: Ibrexafungerp is an orally active, semi-synthetic triterpenoid glucan synthase inhibitor under development for treatment and prevention of VVC. We present the chemistry, mechanism of action, pharmacology, microbiology, and results from clinical studies with ibrexafungerp in women with VVC. Expert opinion: Ibrexafungerp addresses several unmet needs with existing antifungal drugs as a first in a new class of antifungal agents with a novel mechanism of action demonstrating no antifungal cross resistance with azoles, and fungicidal activity against Candida spp., including fluconazole-resistant species. Some of the key attributes of ibrexafungerp related to VVC include oral one-day dosing, high tissue penetration, enhanced activity at low pH seen in the vagina, low risk for clinically significant drug-drug interactions, and a low risk of adverse events. If approved, ibrexafungerp will be the first new antifungal agent available for the treatment of VVC in more than 20 years and the only oral, non-azole antifungal approved for women suffering from VVC.

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Section: Microbiologymentioning

confidence: 98%

Section: Ibrexafungerpmentioning

confidence: 99%

Section: Microbiologymentioning

confidence: 99%

See 1 more Smart Citation

Oral Ibrexafungerp: an investigational agent for the treatment of vulvovaginal candidiasis

Azie¹,

Angulo²,

Dehn

et al. 2020

Expert Opinion on Investigational Drugs

View full text Add to dashboard Cite

show abstract

“…Ibrexafungerp demonstrates broad in vitro activity against a range of Aspergillus spp. isolates and Candida isolates, including C. glabrata and C. auris, which exhibit fks1 and fks2 point mutations associated with resistance to echinocandin antifungals [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. Among Candida species with reduced fluconazole susceptibility, including C. glabrata, C. krusei, C. tropicalis , and C. parapsilosis , MIC 50 ranges with ibrexafungerp were 0.125–1 μg/mL, 0.5–1 μg/mL, <0.03–1 μg/mL, and 0.25–1 μg/mL, respectively.…”

Section: Ibrexafungerpmentioning

confidence: 99%

Ibrexafungerp: A Novel Oral Triterpenoid Antifungal in Development for the Treatment of Candida auris Infections

et al. 2020

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Candida auris is an emerging multidrug-resistant fungal pathogen reported worldwide. Infections due to C. auris are usually nosocomial and associated with high rates of fluconazole resistance and mortality. Echinocandins are utilized as the first-line treatment. However, echinocandins are only available intravenously and are associated with increasingly higher rates of resistance by C. auris. Thus, a need exists for novel treatments that demonstrate potent activity against C. auris. Ibrexafungerp is a first-in-class triterpenoid antifungal agent. Similar to echinocandins, ibrexafungerp inhibits (1→3)-β-D-glucan synthase, a key component of the fungal cell wall, resulting in fungicidal activity against Candida spp. Ibrexafungerp demonstrates broad in vitro activity against various Candida spp. including C. auris and C. auris isolates with fks mutations. Minimum inhibitory concentration (MIC50 and MIC90) values in >400 C. auris isolates were 0.5 μg/mL and 1.0 μg/mL, respectively. Clinical results were reported for two patients with invasive candidiasis or candidemia due to C. auris treated during the CARES (Candidiasis Caused by Candida Auris) trial, an ongoing open-label study. These patients experienced a complete response after treatment with ibrexafungerp. Thus, ibrexafungerp represents a promising new antifungal agent for treating C. auris infections.

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“…Despite sharing the same drug target with echinocandins, IBX exerts its antifungal activity in a way both overlapping with and distinct from what has been uncovered for echinocandin drugs (16). This underlying mechanism explains the finding that IBX has potent activities against not only the wild-type (WT) Candida species but strains carrying fks mutations that confer resistance to echinocandins (12,14,17,18). IBX also differs from echinocandins, which are intravenous (i.v.…”

mentioning

confidence: 98%

Penetration of Ibrexafungerp (Formerly SCY-078) at the Site of Infection in an Intra-abdominal Candidiasis Mouse Model

Lee

Prideaux

Zimmerman

et al. 2020

Antimicrob Agents Chemother

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Ibrexafungerp (IBX), formerly SCY-078, is a novel, oral and intravenous, semisynthetic triterpenoid glucan synthase inhibitor in clinical development for treating multiple fungal infections, including invasive candidiasis. Intra-abdominal candidiasis (IAC) is one of the most common types of invasive candidiasis associated with high mortality largely due to poor drug exposure in infected lesions. To better understand the potential of IBX to treat such infections, we investigated its penetration at the site of infection. Using matrix-assisted laser desorption ionization–mass spectrometry imaging (MALDI-MSI) and laser capture microdissection (LCM)-directed high-pressure liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), we investigated tissue distribution and lesion-specific drug exposure of IBX in a clinically relevant IAC mouse model. After a single-dose treatment, IBX quickly distributed into tissues and efficiently accumulated within lesions. Drug concentrations of IBX within the liver abscesses were almost 100-fold higher than the serum concentration. In addition, drug penetration after repeated treatment of IBX was compared with micafungin. IBX exhibited robust and long-lasting lesion penetration after repeated treatment. These data indicate that IBX penetrates into intra-abdominal abscesses highly efficiently and holds promise as a potential therapeutic option for IAC patients.

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Activity of a Novel 1,3-Beta- d -Glucan Synthase Inhibitor, Ibrexafungerp (Formerly SCY-078), against Candida glabrata

Cited by 29 publications

References 8 publications

Oral Ibrexafungerp: an investigational agent for the treatment of vulvovaginal candidiasis

Oral Ibrexafungerp: an investigational agent for the treatment of vulvovaginal candidiasis

Ibrexafungerp: A Novel Oral Triterpenoid Antifungal in Development for the Treatment of Candida auris Infections

Penetration of Ibrexafungerp (Formerly SCY-078) at the Site of Infection in an Intra-abdominal Candidiasis Mouse Model

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