Ibrexafungerp Versus Placebo for Vulvovaginal Candidiasis Treatment: A Phase 3, Randomized, Controlled Superiority Trial (VANISH 303)

Abstract

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.

Methods: 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 = .001), mycological eradication (49.5% [93/188] vs 19.4% [19/98]; P < .001), and overall success (36.0% [64/178] vs 12.6% [12/95]; P < .001) compared with placebo. Symptom resolution was sustained and further increased with ibrexafungerp compared with placebo (59.6% [112/188] vs 44.9% [44/98]; P = .009) at follow-up. Post hoc analysis showed similar rates of clinical cure and clinical improvement at test-of-cure for Black patients (54.8% [40/73] and 63.4% [47/73], respectively) and patients with a body mass index >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.

Conclusions: Ibrexafungerp provides a promising safe and efficacious oral treatment that mechanistically differs from current azole treatment options for acute VVC.

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

Figure 1.

Patient disposition. Abbreviations: FU, follow-up; ITT, intention-to-treat; mITT, modified intention-to-treat; TOC, test of cure.

Figure 2.

Select efficacy endpoints. A, Efficacy outcomes at TOC visit (day 10): clinical cure (ibrexafungerp, 95/188 patients; placebo, 28/98 patients), mycological eradication (ibrexafungerp, 93/188 patients; placebo, 19/98 patients), and overall success (ibrexafungerp, 64/178 patients; placebo, 12/95 patients). B, Efficacy outcomes at TOC visit (day 10) for patients with C. albicans infections, clinical cure (ibrexafungerp, 88/173 patients; placebo, 25/90 patients), mycological eradication (ibrexafungerp, 89/173 patients; placebo, 17/90 patients), and overall success (ibrexafungerp, 61/163 patients; placebo, 11/88 patients). *P = .001, **P < .001 for comparisons between ibrexafungerp and placebo. Abbreviation: TOC, test of cure.