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Review
. 2020 Aug 25;9(9):539.
doi: 10.3390/antibiotics9090539.

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

Mahmoud Ghannoum  1 , Maiken Cavling Arendrup  2   3   4 , Vishnu P Chaturvedi  5 , Shawn R Lockhart  6 , Thomas S McCormick  1 , Sudha Chaturvedi  5 , Elizabeth L Berkow  6 , Deven Juneja  7 , Bansidhar Tarai  7 , Nkechi Azie  8 , David Angulo  8 , Thomas J Walsh  9
Affiliations
Review

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

Mahmoud Ghannoum et al. Antibiotics (Basel). .

Abstract

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.

Keywords: Candida auris; antifungal; ibrexafungerp; resistance.

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Conflict of interest statement

N.A. and D.A. are employees of and may hold stock in Scynexis, Inc., Jersey City, NJ. T.J.W. received grants for experimental and clinical antimicrobial pharmacology and therapeutics to his institution from Allergan, Amplyx, Astellas, Lediant, Medicines Company, Merck, Scynexis, Tetraphase, and Viosera and has served as consultant to Amplyx, Astellas, Allergan, ContraFect, Gilead, Lediant, Medicines Company, Merck, Methylgene, Pfizer, and Scynexis. V.P.C. received service fees from SCYNEXIS, Inc.; there are no other disclosures. M.C.A., over the past five years, received research grants/contract work (paid to the SSI) from Amplyx, Basilea, Cidara, F2G, Gilead, Novabiotics, Scynexis, and T2Biosystems, and speaker honoraria (personal fee) from Astellas, Gilead, MSD, and SEGES. She is the current chairman of the EUCAST-AFST.

Figures

Figure 1
Figure 1
Structure of ibrexafungerp.
Figure 2
Figure 2
Mechanism of action for ibrexafungerp.
Figure 3
Figure 3
SEM of CA UC (A), SCY treated CA (B), CAS treated CA (C), CAu UC (D), SCY treated CAu (E), CAS treated CAu (F), CG UC (G), SCY treated CG (H), CAS treated CG (I), and TEM of CA UC (J), SCY treated CA (K), CAS treated CA (L), CAu UC (M), SCY treated CAu (N), CAS treated CAu (O), CG UC (P), SCY treated CG (Q), and CAS treated CG (R). (Hager et al., 2018) [51].
See this image and copyright information in PMC

References

    1. Wickes B.L. Analysis of a Candida auris Outbreak Provides New Insights into an Emerging Pathogen. J. Clin. Microbiol. 2020;58 doi: 10.1128/JCM.02083-19. - DOI - PMC - PubMed
    1. Centers for Disease Control and Prevention Tracking Candida Auris. [(accessed on 30 June 2020)]; Available online: https://www.cdc.gov/fungal/candida-auris/tracking-c-auris.html.
    1. Clancy C.J., Nguyen M.H. Emergence of Candida auris: An International Call to Arms. Clin. Infect. Dis. 2016;64:141–143. doi: 10.1093/cid/ciw696. - DOI - PubMed
    1. Chowdhary A., Sharma C., Meis J.F. Candida auris: A rapidly emerging cause of hospital-acquired multidrug-resistant fungal infections globally. PLOS Pathog. 2017;13:e1006290. doi: 10.1371/journal.ppat.1006290. - DOI - PMC - PubMed
    1. Zhu Y., O’Brien B., Leach L., Clarke A., Bates M., Adams E., Ostrowsky B., Quinn M., Dufort E., Southwick K., et al. Laboratory Analysis of an Outbreak of Candida auris in New York from 2016 to 2018: Impact and Lessons Learned. J. Clin. Microbiol. 2019;58 doi: 10.1128/JCM.01503-19. - DOI - PMC - PubMed

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