Ibrexafungerp is the first fourth-generation antifungal drug with a new mechanism of action. It can cover most Candida, Aspergillus, Penicillium multivariate and rare diphasic fungi (such as Histoplasma). It is effective against azole- and echinocandin-resistant Candida, Candida auris, and may be effective against Pneumocystis jiroveci infection (animal model), but is not effective against Mucor and Fusarium. The in vitro antibacterial activity of Ibrexafungerp against various Candida species is similar to that of caspofungin, and its in vitro antibacterial activity against Aspergillus is slightly weaker than that of echinocandin.

Background introduction

Candidal vaginitis, as a common vaginal inflammatory gynecological disease caused by Candida infection, is an important factor affecting women's quality of life. Candidal vaginitis often occurs in the vulva, vagina and other parts, is contagious, and is mainly transmitted through sexual contact. The innovative drug Ibrexafungerp is a fourth-generation antifungal drug with a new mechanism of action. Its effects cover a wide range of common fungi such as Candida, Aspergillus, and Penicillium polymorphum, and even show significant effects on rare dimorphic fungi (such as Histoplasma). In June 2021, Ibrexafungerp was approved by the U.S. Food and Drug Administration (FDA) for the treatment of vulvovaginal candidiasis, bringing good news to many female patients. In November 2022, the FDA further expanded the indications of Ibrexafungerp, approving it for reducing the incidence of recurrent vulvovaginal candidiasis, providing new treatment options for patients with recurrent diseases.

Mechanism of Action

Ibrexafungerp is a triterpenoid antifungal drug that inhibits β-1,3-glucan synthase and destroys its intact cell wall. Glucan synthase is composed of catalytic subunits FKS1 or FKS2 and GTP-binding regulatory subunits Rho1. It is an important component of the fungal cell wall and is related to the formation of β-1,3-d-glucan. The bactericidal activity of Ibrexafungerp against Candida albicans is positively correlated with concentration. The relationship between the contact and sterilization response of Ibrexafungerp to fungal cells and the time course of the drug effect response are still unclear. Animal studies have shown that Ibrexafungerp can be evenly distributed in vaginal tissue, which is beneficial for the treatment of VVC. The specific binding site of Ibrexafungerp for β-1,3-d glucan synthase has not yet been determined, and the antifungal drugs of the echinocandin class also bind to β-1,3-d glucan synthase as a target, and have cross-resistance with Ibrexafungerp, indicating that the binding sites between the two are partially overlapping.

Instructions for use

As the first glycogen synthase inhibitor with a new triterpenoid structure, Ibrexafungerp is a derivative of echinocandin, and it can also be regarded as a fourth-generation antifungal drug with a new mechanism of action. Ibrexafungerp has good efficacy in treating candidal vaginitis and a low recurrence rate. Ibrexafungerp can be administered orally or intravenously. Ibrexafungerp has a high apparent distribution volume and wide tissue distribution, but it cannot penetrate the blood-brain barrier; oral preparations have high bioavailability. As a concentration-dependent drug, the oral preparation of this drug is recommended to be administered once a day. Some studies have shown that it has a weak effect on CYP450 and has few drug interactions.

Toxicology description

A 2-year carcinogenicity study of Ibrexafungerp has not yet been conducted. Ibrexafungerp is non-genotoxic, and no mutagenic or chlamydogenic effects were detected in the in vitro bacterial reverse mutation experiment. The in vitro chromosome aberration experiment and the in vivo bone marrow micronucleus experiment in rats were both negative.