Efficacy and Safety of Oteseconazole in Severe Vulvovaginal Candidiasis Categorized by Candida Species and Previous Genital Tract Infection: A Post Hoc Analysis of a Phase 3 Trial

Purpose: Oteseconazole, a novel selective fungal CYP51 inhibitor, demonstrated superior efficacy over fluconazole for severe vulvovaginal candidiasis (SVVC) in a phase 3 trial. However, whether the efficacy and safety of oteseconazole on SVVC varies by Candida species or previous genital tract infection remains unknown. Patients and Methods: In this exploratory post hoc analysis of a phase 3 trial (NCT04956419), data were analyzed from patients with SVVC receiving oteseconazole (600 mg on day 1 and 450 mg on day 2) or fluconazole (150 mg on days 1 and 4). The primary outcome was therapeutic cure rate at day 28, assessed in subgroups categorized by Candida species (Candida albicans vs. non-Candida albicans) and previous genital tract infection (yes vs. no). Results: Of 319 patients categorized by Candida species or previous genital tract infection (oteseconazole, n = 160; fluconazole, n = 159), 249 were in the Candida albicans subgroup and 70 in the non-Candida albicans subgroup. Regarding previous infection, 107 had previous genital tract infection, while 212 had none. At day 28, the therapeutic cure rates were higher with oteseconazole than with fluconazole across subgroups categorized by Candida species (Candida albicans: 76.56% vs 56.20%, propensity score [PS]-weighted odds ratio [OR] 2.59 [95% CI 1.76, 3.81]; non-Candida albicans: 28.13% vs 13.16%, PS-weighted OR 2.78 [95% CI 1.17, 6.64]) and previous genital tract infection (yes: 61.70% vs 45.00%, PS-weighted OR 2.03 [95% CI 1.18, 3.51]); no: 69.03% vs 46.46%, PS-weighted OR 2.59 [95% CI 1.74, 3.85]). Additionally, the incidence of treatment-emergent adverse events was comparable between oteseconazole and fluconazole across all subgroups. Conclusion: Oteseconazole may offer benefits and is generally well tolerated in patients with SVVC, irrespective of Candida species and previous genital tract infection. However, given the exploratory post hoc nature and the relatively small subgroup sample size, these findings warrant further validation in larger studies.