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

Abstract

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.

Virulence Factors as Promoters of Chronic Vulvovaginal Candidosis: A Review

“…Resistant strains may be treated in the future with new drugs as is the case for ceragenins [136]. Ibrexafungerp is a substance with superior characteristics compared to normal antifungals, with very favorable clinical results in women with VVC [137].…”

In vitro activity of ibrexafungerp and comparators against Candida albicans genotypes from vaginal samples and blood cultures

“…The emergence of azole resistance has prompted the development of new drugs such as ibrexafungerp, an orally and intravenously available beta-d-glucan synthase inhibitor currently under clinical development for treating vulvovaginal candidiasis. Ibrexafungerp has shown good in vitro activity against C. albicans [4e7], but studies focusing on vaginal isolates are limited [8,9]. We assessed the in vitro activity of ibrexafungerp, and comparators, against C. albicans vaginal and blood isolates.…”

Ibrexafungerp: A First-in-Class Oral Triterpenoid Glucan Synthase Inhibitor

“…Currently, there are 12 listed clinical trials for ibrexafungerp (Table 1), eight of which have been completed (https://ClinicalTrials.gov/; accessed on 8 January 2021). Clinical data from at least 1000 participants using both single and multiple daily doses of IBX, as high as 1600 mg, revealed a safe and tolerable profile [108][109][110][111]. Mild adverse events were reported including headaches and gastrointestinal issues such as, diarrhea, nausea, vomiting and abdominal discomfort [108][109][110][111].…”