Efficacy and Safety of Oteseconazole in Recurrent Vulvovaginal Candidiasis.

BACKGROUND: Management of recurrent vulvovaginal candidiasis (RVVC) is an unmet clinical challenge without approved treatment in the United States. Oteseconazole is a novel oral selective inhibitor of fungal CYP51, designed to treat RVVC without off-target toxicities. VIOLET comprised two global, phase 3, multicenter, randomized, double-blind, placebo-controlled trials (CL-011 and CL-012). The primary objective was to evaluate oteseconazole efficacy through week 48. Key secondary objectives evaluated time to first recurrence, safety, and patient-reported outcomes. METHODS: Women with three or more symptomatic acute vulvovaginal candidiasis (VVC) episodes within the previous 12-month period, including the screening episode (in which the VVC episode cleared with fluconazole induction therapy), were randomly assigned 2:1 at baseline (maintenance phase) to 150 mg of oral oteseconazole daily for 7days and then once weekly for 11 weeks or to matching placebo for 12 weeks. Time-to-first-recurrence data were collected during the maintenance phase. Posttreatment follow-up was 36 weeks. RESULTS: Among 656 women (326 in CL-011 and 330 in CL-012), the averaged percentage of participants with one or more RVVC episodes through week 48 was 6.7% (range, 6.5 to 7.4%) in CL-011 and 3.9% (3.7 to 4.6%) in CL-012 in the oteseconazole groups versus 42.8% (41.3 to 45.0%) and 39.4% (38.0 to 42.6%) in the corresponding placebo groups (P<0.001). Among oteseconazole-treated participants in CL-011 and CL-012 who experienced an RVVC episode (n=22), the mean time to recurrence was 45.7 and 47.2 weeks versus 27.8 and 33.1 weeks for placebo-treated participants (n=84), respectively (hazard ratio [95% confidence interval], 0.11 [0.06 to 0.21] for CL-011 and 0.08 [0.04 to 0.17] for CL-012; P<0.001). Types and frequencies of treatment-emergent adverse events (TEAEs) were similar between groups in both trials, with no drug-related serious TEAEs or adverse effects on pregnancy outcomes, liver function, or QT interval. CONCLUSIONS: Oral oteseconazole was effective in preventing acute VVC recurrence and treating RVVC through week 48 in the CL-011 and CL-012 trials, with mostly mild TEAEs. (Funded by Mycovia Pharmaceuticals, Inc., ClinicalTrials.gov numbers, NCT03562156 for CL-011 and NCT03561701 for CL-012.)