Ibrexafungerp for treating vulvovaginal candidiasis

Ibrexafungerp provides activity against a variety of multidrug-resistant fungi, including Candida auris, according to a review of the pharmacokinetics and pharmacodynamics of the medicine published in the journal Drugs in R&D.¹

Ibrexafungerp is a first-in-class triterpenoid antifungal agent in an oral formulation. “Similar to echinocandins, ibrexafungerp inhibits (1→3)-β-d-glucan synthase, a key component of the fungal cell wall, and has both in vitro and in vivo activity against a variety of clinically relevant fungal species, including the yeast Candida and the mold Aspergillus,” wrote author Matthew William McCarthy, MD, from the Department of Medicine at Weill Cornell Medicine in New York City.

Because the drug retains in vitro activity against both echinocandin-resistant and triazole-resistant strains of pathogenic fungi, it is well positioned to address the mounting challenge of drug-resistant invasive fungal infections.

A single-center, open-label phase I study of healthy subjects that assessed the drug–drug interaction potential between ibrexafungerp and the immunomodulator tacrolimus found that co-administration of the two medicines had no effect on the maximum blood concentrations of tacrolimus.²

The study also concluded there was no change in the maximum concentration of tacrolimus in plasma and a 1.4-fold increase in total area under the curve (AUC). This indicates that a dose adjustment for tacrolimus may not be needed when combined with ibrexafungerp, according to McCarthy.

A multicenter, open-label phase II study randomized patients with invasive candidiasis to one of three stepdown therapies: two dosing regimens of oral ibrexafungerp or standard of care following initial echinocandin therapy.³

Satisfactory response rates for the study were 86% in the ibrexafungerp 750-mg arm compared to 71% for either ibrexafungerp 500-mg or standard of care. All treatment regimens were also well tolerated.

A population pharmacokinetic analysis of the study concluded that the ibrexafungerp 750-mg regimen leads to target exposure in roughly 85% of the population.

A follow-up phase II, randomized, double-blind, dose-finding study comparing ibrexafungerp to fuconazole for treating VVC found that 1 month after diagnosis, clinical cure rates were higher for ibrexafungerp than for fuconazole: 70% vs. 50%.⁴

The FDA approved ibrexafungerp after two successful randomized, double-blind, placebo-controlled, phase 3 clinical trials.

In one of the two trials, clinical cure, mycological eradication and clinical improvement at day 25 for ibrexafungerp compared to placebo were 51 vs 29%, 50 vs 19% and 64% vs 37%, respectively.⁵

The primary endpoint of the other trial was clinical cure rate, which was defined as the complete resolution of all signs and symptoms at the test-of-cure visit on day 10. Clinical cure, mycological eradication and clinical improvement for ibrexafungerp compared to placebo were 63% vs. 44%, 59% vs. 30% and 72% vs. 55%, respectively.⁶

Ibrexafungerp is currently being investigated for numerous invasive conditions, including fungemia, as either standalone treatment or in combination with other antimicrobial agents.

References

1. McCarthy MW. Pharmacokinetics and pharmacodynamics of ibrexafungerp. Drugs in R&D. 2022. 22:9–13. doi:org/10.1007/s40268-021-00376-x
2. Wring S, Murphy G, Atiee G,et al. Clinical pharmacokinetics and drug–drug interaction potential for coadministered SCY-078, an oral fungicidal glucan synthase inhibitor, and tacrolimus. Clin Pharmacol Drug Dev. 2019;8(1):60–9.
3. Spec A, Pullman J, Thompson GR, et al. MSG-10: a phase 2 study of oral ibrexafungerp (SCY-078) following initial echinocandin therapy in non-neutropenic patients with invasive candidiasis. J Antimicrob Chemother. 2019;74(10):3056–62. 22.
4. Azie N, Angulo D, Dehn B, et al. Oral ibrexafungerp: an investigational agent for the treatment of vulvovaginal candidiasis. Expert Opin Investig Drugs. 2020;29(9):893–900.
5. Jallow S, Govender NP. Ibrexafungerp: a first-in-class oral triterpenoid glucan synthase inhibitor. J Fungi (Basel). 2021;7(3).
6. Seiler GT, Ostrosky-Zeichner L. Investigational agents for the treatment of resistant yeasts and molds. Curr Fungal Infect Rep. 2021:1–12.