The novel antifungal agent VT-1161 was as effective as fluconazole for the treatment of acute vulvovaginal candidiasis (VVC) and more effective than the latter for preventing recurrence of VVC, according to results of a phase 2a dose-ranging study [NCT01891331] presented by Stephen R. Brand, PhD, Viamet Pharmaceuticals, Inc, Durham, North Carolina, USA.

VT-1161, a novel oral selective inhibitor of fungal CYP51, is being developed to treat mucosal and superficial fungal infections [Hoekstra WJ et al. Bioorg Med Chem Lett. 2014; Warrilow AGS et al. Antimicrob Agents Chemother. 2014]. It is highly active against a wide range of Candida spp, including azole-resistant strains. A phase 2a study showed that VT-1161 was effective and safe in patients with moderate to severe acute VVC.

The present randomized double-blind trial evaluated the efficacy and safety of different doses of oral VT-1161 compared with fluconazole in patients with moderate to severe acute VVC.

Fifty-five patients were randomized to 1 of 4 treatment arms: low-dose VT-1161 (300 mg/d for 3 days; n = 14), middose VT-1161 (600 mg/d for 3 days; n = 12), high-dose VT-1161 (600 mg BID for 3 days; n = 14), or fluconazole 150 mg for 1 day administered as a single dose (n = 15). At baseline, approximately 76% of patients had a positive culture for Candida spp. Demographics and baseline characteristics were similar across all groups.

The outcomes were an effective therapeutic cure, defined as a total acute VVC severity score of 0 or 1 and a negative Candida culture assessed at day 28, as well as the ability to prevent mycologic and clinical recurrence at 5 months after study treatment was stopped. In the intention-to-treat population, the rates of an effective clinical cure were 71%, 83%, 86%, and 78% in the low-, mid-, and high-dose VT-1161 arms and fluconazole arm, respectively. Furthermore, the rates of mycologic cure were 100%, 92%, 93%, and 73% in these 4 arms, respectively.

At the 5-month follow-up, none of the patients in the VT-1161 arms had a positive Candida culture, compared with 46% of patients in the fluconazole arm. Clinical recurrences that required retreatment during the trial occurred in 47% of the fluconazole patients vs 14% of the low-dose VT-1161 patients; none occurred in the mid- and high-dose VT-1161 patients.

No patients in the intention-to-treat population discontinued participation in the study through the 6-month follow-up. Reported adverse events were mild and considered unrelated to the study drug. No clinically significant changes in vital signs, physical findings, electrocardiograms, or laboratory parameters were observed.

Overall, this study showed that VT-1161 provided a similar effective therapeutic cure at day 28 as fluconazole, but at the mid- and high doses, VT-1161 was more effective in preventing disease recurrence. This latter finding suggests that VT-1161 may have a role in treating recurrent VVC, for which there is no approved therapy, according to the investigators. Indeed, this is now being investigated in the phase 2b randomized REVIVE trial [NCT02267382] in patients with recurrent VVC in the United States.