Ibrexafungerp: A potential solution for intolerance to standard antifungals?

Patients who are refractory or intolerant to currently approved antifungal therapies exhibited a positive response to the novel triterpenoid antifungal ibrexafungerp, according to interim analysis results of the phase III FURI trial.

“Overall … over three-quarters of the patients had a good response with complete or partial response or stable disease,” commented Professor George Thompson from the University of California Davis School of Medicine, Sacramento, California, US, who presented the findings at ID Week 2022.

The multicentre (27 centres in the UK, US, and EU) study included 113 patients who had proven or probable severe mucocutaneous candidiasis, invasive candidiasis, disseminated or invasive dimorphic fungi, or chronic or invasive aspergillosis. To be included, they needed to be refractory, intolerant, or experienced toxicity when exposed to ≥1 currently approved standard-of-care (SoC) antifungal treatments. Patients unable to receive oral or continued intravenous (IV) antifungal therapy could also be included.

The patients were treated with ibrexafungerp (750 mg BID for 2 days followed by 750 mg QD for up to 180 days*). A majority of the patients (49.6 percent) had invasive candidiasis or candidemia, 28.3 percent had mucocutaneous candidiasis, 12.3 percent vulvovaginal candidiasis, and 9.7 percent aspergillosis. About two-thirds of patients were refractory to SoC antifungal treatments.

Overall, 56.5 percent of patients treated with ibrexafungerp experienced complete or partial response or clinical improvement. [ID Week 2022, abstract 871]

When evaluated by type of fungal infection, complete or partial response or clinical improvement was experienced by 62.5 percent of patients with invasive candidiasis or candidemia, 53.1 percent with mucocutaneous candidiasis, 71.4 percent with vulvovaginal candidiasis, and 36.3 percent with aspergillosis.

About 26 percent of patients had stable disease, which was achieved by 21.4 percent of patients (n=12) with invasive candidiasis or candidemia, 34.4 percent (n=11) with mucocutaneous candidiasis, 18.1 percent (n=2) with aspergillosis, and 7.1 percent (n=1) with vulvovaginal candidiasis.

Stable disease, while often viewed negatively, could be interpreted as a favourable response as patients are still able to continue treatment, Thompson pointed out.

About 11 percent of patients experienced disease progression (including two with vulvovaginal candidiasis who did not meet the criteria for clinical improvement). These included four patients with invasive candidiasis or candidemia, four with aspergillosis, and three with mucocutaneous candidiasis. Data was indeterminate in six patients. One death was documented in a patient with invasive candidiasis or candidemia.

The most common treatment-related adverse events (AEs) with ibrexafungerp use were of gastrointestinal origin, which generally emerged once the daily dose was initiated. According to Thompson, the issue of diarrhoea tended to improve if the dosage was split (half dose each in the morning and evening).

“[I]brexafungerp appears to provide a favourable therapeutic response for most patients with a variety of serious fungal infections. I think this is really a good option for patients who have failed or are intolerant to currently available regimens and certainly a welcome addition for those who would otherwise need long-term IV therapy,” he said.