Phase 2 Randomized Study of Oral Ibrexafungerp Versus Fluconazole in Vulvovaginal Candidiasis

Abstract

Background: Vulvovaginal candidiasis affects approximately 75% of women in their lifetime. Approved treatment options are limited to oral or topical azoles. Ibrexafungerp, a novel, first-in-class oral triterpenoid glucan synthase inhibitor, has demonstrated broad fungicidal Candida activity and a favorable tolerability profile. The primary objective of this dose-finding study was to identify the optimal dose of oral ibrexafungerp in patients with acute vulvovaginal candidiasis.

Methods: Patients with vulvovaginal signs and symptoms score ≥7 were randomized equally to 6 treatments groups: 5 treatment doses of oral ibrexafungerp or oral fluconazole 150 mg. The primary endpoint was the percentage of patients with a clinical cure (complete resolution of vulvovaginal signs and symptoms) at the test-of-cure visit (day 10).

Results: Overall, 186 patients were randomized into the 6 treatment groups. Results, using the modified intent-to-treat population (baseline positive culture), are reported for ibrexafungerp 300 mg twice daily (BID) for 1 day (n = 27), which was the dose selected for phase 3 studies, and fluconazole 150 mg for 1 day (n = 24). At day 10, the clinical cure rates for ibrexafungerp and fluconazole were 51.9% and 58.3%, respectively; at day 25, patients with no signs or symptoms were 70.4% and 50.0%, respectively. During the study ibrexafungerp patients required less antifungal rescue medications compared with fluconazole (3.7% vs 29.2%, respectively). Ibrexafungerp was well tolerated, with the most common treatment-related adverse events being mild gastrointestinal events.

Conclusions: Ibrexafungerp is a well-tolerated novel antifungal with comparable efficacy to fluconazole in the treatment of acute vulvovaginal candidiasis.

Clinical trials registration: NCT03253094.

Keywords: Candida albicans; SCY-078; fluconazole; ibrexafungerp; vulvovaginal candidiasis.

Figure 1.

Patient disposition. Abbreviations: BID, twice daily; QD, once daily.

Figure 2.

Efficacy outcomes for ibrexafungerp 300 mg BID for 1 day from baseline to TOC (day 10), and follow-up (day 25) visits. A, Clinical cure, VSS scores ≤1, and rate of mycological eradication at TOC visit (day 10). B, VSS score of 0, VSS scores ≤1, and rate of mycological eradication at follow-up (day 25). C, Percentage of patients who required antifungal rescue medication while participating in the study. Clinical cure was defined as a complete resolution of VSS of acute vulvovaginal candidiasis at the TOC visit (day 10); the VSS scale is a standardized, predefined assessment for which each sign and symptom was given a numerical rating based on severity (absent = 0, mild = 1, moderate = 2, and severe = 3) to calculate a total composite score (range, 0–18); mycological eradication was defined as a negative fungal culture. Rescue medications used in these 2 treatment arms included fluconazole, Lotrisone (clotrimazole-betamethasone dipropionate), and terconazole. Abbreviations: BID, twice daily; TOC, test-of-cure; VSS, vulvovaginal signs and symptoms.