Ibrexafungerp (DB12471): A Comprehensive Monograph on a First-in-Class Triterpenoid Antifungal

Executive Summary

Ibrexafungerp represents a significant advancement in antifungal therapy, being the first approved agent in a novel class, the triterpenoids, in over two decades.[1] Marketed under the brand name Brexafemme®, it is a semi-synthetic derivative of the natural product enfumafungin, developed to address the growing challenges of fungal infections, particularly those caused by resistant pathogens.[1] It is currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of acute vulvovaginal candidiasis (VVC) and for the reduction in the incidence of recurrent VVC (RVVC) in adult and post-menarchal pediatric females.[3]

The pharmacological distinction of ibrexafungerp lies in its mechanism of action. It inhibits the fungal enzyme β-(1,3)-D-glucan synthase, a critical component for cell wall synthesis, similar to the echinocandin class of antifungals.[3] However, its unique triterpenoid structure allows it to bind to a site on the enzyme that is distinct from that of the echinocandins.[3] This structural and mechanistic nuance is of profound clinical importance, as it confers potent activity against a broad spectrum of fungal pathogens, including many strains that have developed resistance to both azoles and echinocandins.[8] Its spectrum includes most

Candida species, including the multidrug-resistant Candida auris, and Aspergillus species.[13]