Ibrexafungerp expands salvage antifungal treatment options as a pill

For patients with fungal diseases that preclude receiving standard treatment or IV antifungals primarily due to refractoriness or resistance, ibrexafungerp can serve as an effective salvage treatment given orally, offering a positive risk-benefit ratio up to the final data cut-off in the FURI trial.

“You run out of options, so you may see resistance in patients with some STAT defects or other mutations, and they can't fend off the Candida after really going through every licensed drug out there. That is where we then used ibrexafungerp in the study,” said Professor Oliver Cornely, a medical mycologist at the University Hospital of Cologne, North Rhine-Westphalia, Germany, at ESCMID Global 2025. “Before I would treat such a patient with, for example, amphotericin B, I would rather go for something way less toxic and oral instead of IV.”

In the salvage setting of the phase III, single-arm study, treating a variety of fungal diseases with the oral triterpenoid antifungal ibrexafungerp resulted in an overall global success rate of 60.9 percent at either the end of treatment or the test of cure (TOC), with responses determined by an independent data review committee.

Serious treatment-emergent adverse events deemed related to treatment were infrequent, with a rate of 3.4 percent. There were no deaths related to the study drug per investigator assessment. [ESCMID Global 2025, abstract O0514]

“Ibrexafungerp was generally well tolerated, so the treatment has a positive risk-benefit ratio for a broad spectrum of fungal infections,” added Cornely.

Efficacy by disease

“Global success rates for ibrexafungerp were in the two-thirds range for both acute and chronic invasive candidiasis (IC), which included complete and partial responses. It was even slightly over 80 percent for vulvovaginal candidiasis (VVC), which included only complete responses,” said Cornely regarding the three most common diseases in the FURI population.

Precisely, the global success rates were 65.6 percent for acute and 69.8 percent for chronic IC, after patients received ibrexafungerp for a median of 18 days and 106 days, respectively.

In FURI, ibrexafungerp was dosed at 375 mg twice daily on 3 days over a 7-day period for the treatment of severe VVC. At the TOC visit, 10 days after treatment completion, the global success rate was 81.3 percent.

The 233 patients enrolled in FURI (mean age 53.6 years, 54.9 percent female) had either acute or chronic IC, acute or chronic severe mucocutaneous candidiasis, invasive pulmonary aspergillosis, chronic pulmonary aspergillosis, allergic bronchopulmonary aspergillosis, disseminated or invasive dimorphic fungal infections, or infections caused by other emerging fungi.

The most common reasons for enrolment in the trial were antifungal resistance (57.5 percent) and refractory disease (54.9 percent), followed by intolerance (12.4 percent), relapse after initial improvement (7.7 percent), and toxicities (7.3 percent).

Not an echinocandin

While ibrexafungerp represents the first oral triterpenoid antifungal, it acts by inhibiting β-1,3-D-glucan synthase, similar to how echinocandins disrupt fungal cell wall biosynthesis. [Antimicrob Agents Chemother 2017;61:e01961-16]

“Ibrexafungerp is not an echinocandin. There are differences apart from just being another class. The mode of action is the same, but the spectra of activity are different,” said Cornely. “There are more than just Candida and Aspergillus, as we would say that’s what echinocandins do. It has activity, for example, against echinocandin-resistant pathogens.”

It is thus postulated that they have nonidentical binding sites on glucan synthase. [Antimicrob Agents Chemother 2017;61:e00833-17]