Ibrexafungerp versus placebo for vulvovaginal candidiasis treatment: a phase 3, randomized, controlled superiority trial (VANISH 303)

Background Current treatment of vulvovaginal candidiasis (VVC) is largely limited to azole therapy. Ibrexafungerp is a first-in-class triterpenoid antifungal with broad-spectrum anti-Candida fungicidal activity. The objective of this study was to evaluate the efficacy and safety of ibrexafungerp compared with placebo in patients with acute VVC. Study design Patients were randomly assigned 2:1 to receive ibrexafungerp (300 mg twice for 1 day) or placebo. The primary endpoint was the percentage of patients with a clinical cure (complete resolution of vulvovaginal signs and symptoms [VSS]=0) at test-of-cure (day 11±3). Secondary endpoints included the percentage of patients with mycological eradication, overall success (clinical cure and mycological eradication), clinical improvement (VSS≤1) at test-of-cure, and symptom resolution at follow-up (day 25±4). Results Patients receiving ibrexafungerp had significantly higher rates of clinical cure (50.5% [95/188] vs 28.6% [28/98]; P=0.001), mycological eradication (49.5% [93/188] vs 19.4% [19/98]; P 35 (54.5% [24/44] and 68.2% [30/44], respectively) compared with overall rates. Ibrexafungerp was well tolerated. Adverse events were primarily gastrointestinal and mild in severity. Conclusion Ibrexafungerp provides a promising safe and efficacious oral treatment that mechanistically differs from current azole treatment options for acute VVC.