Reviewing the mechanism of action and results of clinical studies on the antifungal drug ibrexafungerp
https://doi.org/10.17749/2313-7347/ob.gyn.rep.2024.500
Abstract
Introduction. Vulvovaginal candidiasis is an extremely common pathology of the female genital organs, leading to a long-term recurrent course and multiple complications. Although currently it is widely known about developing antibiotic resistance of bacterial pathogens, it is necessary to remember about similar phenomenon observed in other groups of infectious agents. In this regard, fungal infection also requires development of new therapeutic techniques and medicinal antifungal drugs, such as ibrexafungerp.
Aim: to analyze available publications revealing the mechanism of action, efficacy, antifungal spectrum and results of clinical trials for a new oral antifungal drug ibrexafungerp.
Materials and Methods. A search for publications in the electronic databases PubMed, eLibrary and ClinicalTrials.gov, published over the last 25 years was conducted using the following keywords in Russian and English: “candidiasis”, “vulvovaginal candidiasis”, “antifungal drugs”, “ibrexafungerp”, “clinical trials”, “mechanism of action”. Articles were assessed according to PRISMA guidelines. The titles and abstracts of identified publications were independently reviewed to retrieve relevant full text studies. After the selection procedure, 46 articles were included in the review.
Results. This review provides information on the creation of the drug ibrexafungerp, its mechanism of action, the activity against a relatively wide range of pathogens, as well as the results from 13 ongoing and completed clinical trials in patients with fungal infection.
Conclusion. The analysis of ibrexafungerp-related clinical studies showed its good oral bioavailability, high antifungal efficacy, so that its one-day dosage may further eliminate a need for unnecessarily long hospitalization and complex dosing schedules, thereby increasing adherence to therapy and odds for treatment success.
Keywords
About the Authors
L. I. TagirovaRussian Federation
Leysan I. Tagirova, MD, Assistant
Department of Obstetrics and Gynecology
450008; 3 Lenin Str.; Ufa
K. R. Farvazova
Russian Federation
Kamila R. Farvazova, Student
Faculty of General Medicine
450008; 3 Lenin Str.; Ufa
D. R. Valeeva
Russian Federation
Daniia R. Valeeva, Student
450008; 3 Lenin Str.; Ufa
M. D. Orlova
Russian Federation
Maria D. Orlova, Student
Faculty of Pediatrics
450008; 3 Lenin Str.; Ufa
I. A. Gubaidullin
Russian Federation
Irik A. Gubaidullin, Student
Faculty of General Medicine
450008; 3 Lenin Str.; Ufa
A. M. Tulyabaeva
Russian Federation
Adelina M. Tulyabaeva, Student
Faculty of General Medicine
450008; 3 Lenin Str.; Ufa
A. R. Abdulmanova
Russian Federation
Ailina R. Abdulmanova, Student
Faculty of General Medicine
450008; 3 Lenin Str.; Ufa
R. V. Tryapko
Russian Federation
Ruslan V. Tryapko, MD, Assistant
Department of Obstetrics and Gynecology
344022; 29 Nakhchivansky Lane; Rostov-on-Don
D. A. Shelyginsky
Russian Federation
Daniil A. Shelyginsky, Student
Faculty of General Medicine
460000; 6 Sovetskaya Str.; Orenburg
A. R. Khanafieva
Russian Federation
Anzhelika R. Khanafieva, Student
Faculty of General Medicine
460000; 6 Sovetskaya Str.; Orenburg
N. G. Semenova
Russian Federation
Nastasia G. Semenova, Student
Faculty of General Medicine
450008; 3 Lenin Str.; Ufa
E. M. Takiullin
Russian Federation
Eduard M. Takiullin, Student
Faculty of General Medicine
450008; 3 Lenin Str.; Ufa
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What is already known about this subject?
► Although conventional vulvovaginal candidiasis (VVC) treatment regimens are effective in relieving the disease symptoms, the data from long-term therapy are characterized by a high recurrence rate.
► The most common VVC causative agent is the polymorphic opportunistic fungus Candida albicans of the Cryptococcaceae family (76–89 %).
► The negative dynamics for VVС incidence last years reported in the studies is associated with rise in infection with Candida non-albicans strains resistant to most antifungal drugs.
What are the new findings?
► Preclinical studies of Ibrexafungerp (IBX) have demonstrated high antifungal activity against an extremely wide range of Candida isolates, including in vitro susceptibility to this drug observed in a number of echinocandin-resistant isolates such as C. albicans, C. parapsilosis, C. tropicalis, C. auris, C. krusei, C. glabrata, C. guilliermondii, C. lusitaniae, C. inconspicua. However, fungicidal activity against echinocandin-resistant FKS gene mutants (C. albicans, C. krusei, C. tropicalis, C. glabrata, C. auris) varied.
► Summarizing the results of phase II and III clinical trials, it can be argued that the IBX is effective against resistant fungal strains. The overall effectiveness in achieving clinical remission after IBX administration compared to standard treatment is 69.75 % versus 61 % for traditional methods of treatment.
► The percentage of patients with observed clinical recovery receiving IBX was 66.55 % that markedly exceeds that of in placebo group – 47.46 %.
How might it impact on clinical practice in the foreseeable future?
► High IBX antifungal efficacy and a one-day dosage may further eliminate a need for unnecessarily long hospitalization and complex dosing schedules, thereby increasing adherence to therapy and odds for treatment success.
► The advantages related IBX such as extremely low toxicity, increased activity at low pH values accounting for high activity upon inflammation, long-term maintenance of a high drug concentration in body tissues during invasive diseases, low risk of undesirable drug interactions, allowing application of drug combinations and treatment of patients with multiple concomitant diseases, predict a marked success for this drug in clinical practice.
Review
For citations:
Tagirova L.I., Farvazova K.R., Valeeva D.R., Orlova M.D., Gubaidullin I.A., Tulyabaeva A.M., Abdulmanova A.R., Tryapko R.V., Shelyginsky D.A., Khanafieva A.R., Semenova N.G., Takiullin E.M. Reviewing the mechanism of action and results of clinical studies on the antifungal drug ibrexafungerp. Obstetrics, Gynecology and Reproduction. 2024;18(2):232-245. (In Russ.) https://doi.org/10.17749/2313-7347/ob.gyn.rep.2024.500

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