Promising antimycotics for the treatment of invasive infections | CMAC

Promising antimycotics for the treatment of invasive infections

Clinical Microbiology and Antimicrobial Chemotherapy. 2023; 25(2):165-170

​ Ortenberg E.А.
10.36488/cmac.2023.2.165-170
fosmanogepix ibrexafungerp olorofim opelconazole rezafungin invasive mycoses antimycotics
Section
Antimicrobials
Type
Review
Publication
Clinical Microbiology and Antimicrobial Chemotherapy. 2023; 25(2):165-170

Abstract

This paper provides a review of the largest studies (over the period of 2018 to 2023) of promising novel antimycotics and their possible role in the treatment of invasive mycoses, including infections caused by resistant Candida and Aspergillus isolates.

Ortenberg E.А.

Tyumen State Medical University, Tyumen, Russia

  • 1. Fisher M.C., Alastruey-Izquierdo A., Berman J., Bicanic T., Bignell E.M., Bowyer P., et al. Tackling the emerging threat of antifungal resistance to human health. Nat Rev Microbiol. 2022;20:557-571. DOI: 10.1038/s41579022-00720-1
  • 2. Logan A., Wolfe A., Williamson J.C. Antifungal resistance and the role of new therapeutic agents. Curr Infect Dis Rep. 2022;24(9):105-116. DOI: 10.1007/s11908-02200782-5
  • 3. Hoenigl M., Sprute R., Egger M., Arastehfar A., Cornely O.A., Krause R., et al. The antifungal pipeline: fosmanogepix, ibrexafungerp, olorofim, opelconazole, and rezafungin. Drugs. 2021;81(15):1703-1729. DOI: 10.1007/s40265-021-01611-0
  • 4. Van Daele R., Spriet I., Wauters J., Maertens J., Mercier T., Van Hecke S., Brüggemann R. Antifungal drugs: what brings the future? Med Mycol. 2019;57:S328-S343. DOI: 10.1093/mmy/myz012
  • 5. Gintjee T.J., Donnelley M.A., Thompson G.R. III. Aspiring antifungals: review of current antifungal pipeline developments. J Fungi. 2020;6(1):28. DOI: 10.3390/jof6010028
  • 6. Rauseo A.M., Coler-Reilly A., Larson L., Spec A. Hope on the horizon: novel fungal treatments in development. Open Forum Infect Dis. 2020;7(2):ofaa016. DOI: 10.1093/ofid/ofaa016
  • 7. Lamoth F., Lewis R.E., Kontoyiannis D.P. Investigational antifungal agents for invasive mycoses: a clinical perspective. Clin Infect Dis. 2022;75(3):534-544. DOI: 10.1093/cid/ciab1070
  • 8. Sandison T., Ong V., Lee J., Thye D. Safety and pharmacokinetics of CD101 IV, a novel echinocandin, in healthy adults. Antimicrob Agents Chemother. 2017;61(2):e01627-16. DOI: 10.1128/AAC.01627-16
  • 9. Garcia-Effron G. Rezafungin – mechanisms of action, susceptibility and resistance: similarities and differences with the other echinocandins. J Fungi. 2020;6(4):262. DOI: 10.3390/jof6040262
  • 10. Thompson G.R. III, Soriano A., Skoutelis A., Vazquez J.A., Honore P.M., Horcajada J.P., et al. Rezafungin versus caspofungin in a phase 2, randomized, double-blind study for the treatment of candidemia and invasive candidiasis: the STRIVE trial. Clin Infect Dis. 2021;73(11):e3647-e3655. DOI: 10.1093/cid/ciaa1380
  • 11. Zhao Y., Perlin S.D. Review of the novel echinocandin antifungal rezafungin: animal studies and clinical data. J Fungi. 2020;6(4):192. DOI: 10.3390/jof6040192
  • 12. Cidara Therapeutics, Inc. Available at: www.cidara.com. Accessed March 2023.
  • 13. Wiederhold N.P. Pharmacodynamics, mechanisms of action and resistance, and spectrum of activity of new antifungal agents. J Fungi. 2022;8(8):857. DOI: 10.3390/jof8080857
  • 14. Scynexis, Inc. Available at: www.scynexis.com. Accessed March 2023.
  • 15. Mesquida A., Díaz-García J., Sánchez-Carrillo C., Muñoz P., Escribano P., Guinea J. In vitro activity of ibrexafungerp against Candida species isolated from blood cultures. Determination of wild-type populations using the EUCAST method. Clin Microbiol Infect. 2022;28(1):140. e1-140.e4. DOI: 10.1016/j.cmi.2021.09.030
  • 16. Nunnally N.S., Etienne K.A., Angulo D., Lockhart S.R., Berkow E.L. In vitro activity of ibrexafungerp, a novel glucan synthase inhibitor against Candida glabrata isolates with FKS mutations. Antimicrob Agents Chemother. 2019; 63(11):e01692-19. DOI: 10.1128/AAC.01692-19
  • 17. McCarthy M.W. Pharmacokinetics and pharmacodynamics of ibrexafungerp. Drugs. 2022;22(1):9-13. DOI: 10.1007/s40268-021-00376-x
  • 18. Wring S.A., Randolph R., Park S., Abruzzo G., Chen Q., Flattery A., et al. Preclinical pharmacokinetics and pharmacodynamic target of SCY-078, a first-in-class orally active antifungal glucan synthesis inhibitor, in murine models of disseminated candidiasis. Antimicrob Agents Chemother. 2017;61(4):e02068-16. DOI: 10.1128/AAC.02068-16
  • 19. Barat S.A. Efficacy of ibrexafungerp (formerly SCY-078) in a murine treatment model of Pneumocystis pneumonia. Proceedings of the ASM Microbe; San Francisco, CA, USA. June 20-24, 2019.
  • 20. Ghannoum M., Long L., Larkin E.L., Isham N., Sherif R., Borroto-Esoda K., et al. Evaluation of the antifungal activity of the novel oral glucan synthase inhibitor SCY078, singly and in combination, for the treatment of invasive aspergillosis. Antimicrob Agents Chemother. 2018;62(6):e00244-18. DOI: 10.1128/AAC.00244-18
  • 21. Quindós G., Miranda-Cadena K., San-Millán R., BorrotoEsoda K., Cantón E., Linares-Sicilia M.J., et al. In vitro antifungal activity of ibrexafungerp (SCY-078) against contemporary blood isolates from medically relevant species of Candida: A European study. Front Cell Infect Microbiol. 2022;12:906563. DOI: 10.3389/fcimb.2022.906563
  • 22. Pappas P.G. Oral ibrexafungerp outcomes by fungal disease in patients from an interim analysis of a phase 3 openlabel study (FURI). Open Forum Infect Dis. 2021;8(Suppl. 1):S73-S74. DOI: 10.1093/ofid/ofab466.123
  • 23. Spec A., Pullman J., Thompson G.R. III, Powderly W.G., Tobin E.H., Vazquez J., et al. MSG-10: a phase 2 study of oral ibrexafungerp (SCY-078) following initial echinocandin therapy in non-neutropenic patients with invasive candidiasis. J Antimicrob Chemother. 2019;74:30563062. DOI: 10.1093/jac/dkz277
  • 24. Hata K., Horii T., Miyazaki M., Watanabe N.A., Okubo M., Sonoda J., et al. Efficacy of oral E1210, a new broadspectrum antifungal with a novel mechanism of action, in murine models of candidiasis, aspergillosis, and fusariosis. Antimicrob Agents Chemother. 2011;55(10):4543-4551. DOI: 10.1128/AAC.00366-11
  • 25. Shaw K.J., Ibrahim A.S. Fosmanogepix: a review of the first-in-class broad spectrum agent for the treatment of invasive fungal infections. J Fungi. 2020;6(4):239. DOI: 10.3390/jof6040239
  • 26. Pfaller M.A., Huband M.D., Flamm R.K., Bien P.A., Castanheira M. In vitro activity of APX001A (manogepix) and comparator agents against 1,706 fungal isolates collected during an international surveillance program in 2017. Antimicrob Agents Chemother. 2019;63(8):e00840-19. DOI: 10.1128/AAC.00840-19
  • 27. Pfaller M.A., Huband M.D., Rhomberg P.R., Bien P.A., Castanheira M. Activities of manogepix and comparators against 1,435 recent fungal isolates collected during an international surveillance program (2020). Antimicrob Agents Chemother. 2022;66(11):e0102822. DOI: 10.1128/aac.01028-22
  • 28. U.S. National Library of Medicine. ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT04148287. Accessed March 2023.
  • 29. U.S. National Library of Medicine. ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT04240886. Accessed March 2023.
  • 30. Gebremariam T., Gu Y., Alkhazraji S., Youssef E., Shaw K.J., Ibrahim A.S. The combination treatment of fosmanogepix and liposomal amphotericin B is superior to monotherapy in treating experimental invasive mold infections. Antimicrob Agents Chemother. 2022;66:e0038022. DOI: 10.1128/aac.00380-22
  • 31. U.S. National Library of Medicine. ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT03604705. Accessed March 2023.
  • 32. du Pre S., Birch M., Law D., Beckmann N., Sibley G.E.M., Bromley M.J., et al. The dynamic influence of olorofim (F901318) on the cell morphology and organization of living cells of Aspergillus fumigatus. J Fungi. 2020;6:47. DOI: 10.3390/jof6020047
  • 33. Thyssen Astvad K.M., Jørgensen K.M., Hare R.K., Datcu R., Arendrup M.C. Olorofim susceptibility testing of 1,423 Danish mold isolates obtained in 2018-2019 confirms uniform and broad-spectrum activity. Antimicrob Agents Chemother. 2021;65(1):e01527-20. DOI: 10.1128/AAC.01527-20
  • 34. European Medicines Agency. Available at: www.ema.europa.eu/en/medicines/human/orphan-designations/eu-3-16-1738. Accessed March 2023.
  • 35. F2G, Inc. Available at: https://f2g.com//press_releases. Accessed March 2023.
  • 36. Maertens J., Verweij P.E., Lanuza E.F., Harvey E.L., Dane A., Zinzi D., et al. Olorofim for the treatment of invasive mould infections in patients with limited or no treatment options: comparison of interim results from a Phase 2B open-label study with outcomes in historical control populations (NCT03583164, FORMULA-OLS, Study 32). Open Forum Infect Dis. 2022;9(Suppl. 2):ofac492.063. DOI: 10.1093/ofid/ofac492.063
  • 37. Murray A., Cass L., Ito K., Pagani N., Armstrong-James D., Dalal P., et al. PC945, a novel inhaled antifungal agent, for the treatment of respiratory fungal infections. J Fungi. 2020;6(4):373. DOI: 10.3390/jof6040373
  • 38. Colley T., Alanio A., Kelly S.L., Sehra G., Kizawa Y., Warrilow A.G.S., et al. In vitro and in vivo antifungal profile of a novel and long-acting inhaled azole, PC945, on Aspergillus fumigatus infection. Antimicrob Agents Chemother. 2017;61(5):e02280-16. DOI: 10.1128/AAC.02280-16
  • 39. Cass L., Murray A., Davis A., Woodward K., Albayaty M., Ito K., et al. Safety and nonclinical and clinical pharmacokinetics of PC945, a novel inhaled triazole antifungal agent. Pharmacol Res Perspect. 2021;9(1):e00690. DOI: 10.1002/prp2.690
  • 40. Hoenigl M. Invasive fungal disease complicating COVID-19: when it rains it pours. Clin Infect Dis. 2021;73(7):e1645-e1648. DOI: 10.1093/cid/ciaa1342
  • 41. Arastehfar A., Carvalho A., van de Veerdonk F.L., Jenks J.D., Koehler P., Krause R., et al. COVID-19 associated pulmonary aspergillosis (CAPA): from immunology to treatment. J Fungi. 2020;6(2):91. DOI: 10.3390/jof6020091
  • 42. Sharma N., Wani S.N., Behl T., Singh S., Zahoor I., Sehgal A., et al. Focusing COVID-19-associated mucormycosis: a major threat to immunocompromised COVID-19. Environ Sci Pollut Res Int. 2023;30(4):9164-9183. DOI: 10.1007/s11356-022-24032-2
  • 43. Ngan N.T.T., Flower B., Day J.N. Treatment of cryptococcal meningitis: how have we got here and where are we going? Drugs. 2022;82(12):1237-1249. DOI: 10.1007/s40265-022-01757-5
  • 44. Matinas BioPharma Holdings, Inc. Available at: www.matinasbiopharma.com/lnc-technology/lnc-platform. Accessed March, 2023.
  • 45. Aigner M., Lass-Flörl С. Encochleated amphotericin B: is the oral availability of amphotericin B finally reached? J Fungi. 2020;6(2):66. DOI: 10.3390/jof6020066
  • 46. Kibathi L., Kumar P., Lionakis M., Urban A., Ferre E., McManus M., et al. A phase IIa efficacy, safety, tolerability and pharmacokinetic (PK) study of encochleated amphotericin B in patients with mucocutaneous (esophogeal, oropharyngeal, vulvovaginal) candidiasis who are refractory or intolerant to standard non-intravenous therapies. Open Forum Infect. Dis. 2018;5:S435-S436. DOI: 10.1093/ofid/ofy210.1244
  • 47. U.S. National Library of Medicine. ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/nct04031833. Accessed April 22, 2022.
Views
0 Abstract
0 PDF
0 Crossref citations
Shared