Oral triterpenoid antifungal works against recurrent vulvovaginal candidiasis

Treatment with the first-in-class oral nonazole, triterpenoid antifungal ibrexafungerp appears to be efficacious and well-tolerated in patients with recurrent vulvovaginal candidiasis, as shown in the phase III CANDLE study.

In the intent-to-treat population, clinical success (ie, absence of mycologically proven, presumed, or suspected recurrence) at week 24 was achieved in 65.4 percent of ibrexafungerp-treated patients vs 53.1 percent of placebo-treated patients (relative risk [RR], 1.24, 95 percent confidence interval [CI], 1.034–1.486; p=0.020). [Am J Obstet Gynecol 2025;233:617.e1-617.e18]

Significantly more patients in the ibrexafungerp vs the placebo group were free of mycologically proven recurrence by week 28 (70.8 percent vs 58.5 percent; RR, 1.22, 95 percent CI, 1.032–1.430; p=0.019).

Treatment benefit was sustained over the 4 months following last dose for both the clinical success (57.7 percent vs 46.2 percent; RR, 1.26, 95 percent CI, 1.017–1.555; p=0.034) and no mycologically proven recurrence (65.4 percent vs 53.8 percent; RR, 1.22, 95 percent CI, 1.021–1.456; p=0.029).

In terms of safety, treatment-emergent adverse events (AEs) occurred in 64.6 percent of ibrexafungerp-treated patients and in 58.5 percent of those who received placebo. The most common AEs in both the ibrexafungerp and placebo groups were headache, bacterial vaginosis, and diarrhoea. These events were mostly mild in severity.

Treatment-related AEs were documented in 14.6 percent and 6.9 percent of patients in the ibrexafungerp and placebo groups, respectively. No AEs in the ibrexafungerp group led to treatment or study discontinuation

The present data position ibrexafungerp as a needed addition to the therapeutic armamentarium for the management of recurrent vulvovaginal candidiasis, according to the study authors.

“Recurrent vulvovaginal candidiasis management encompasses many challenges including limited treatment options, substantial burden on overall health, quality of life, work productivity, and frequent relapses after stopping therapy. Additionally, rates of resistance to azole antifungals are increasing, especially among non-albicans C spp., and oral treatment options for fluconazole-resistant Candida spp. are limited,” the authors noted.

“[Ibrexafungerp] addresses several unmet needs for vulvovaginal candidiasis treatment by providing a nonazole mechanism of action with a broad-spectrum of activity, fungicidal activity against Candida, high penetration into target tissues, and antifungal potency not affected by vaginal pH,” they added. 

CANDLE

The study included 260 patients (average age 34 years, 90 percent White, average BMI 25 kg/m²) with recurrent vulvovaginal candidiasis who were experiencing an acute infection episode. These patients received three doses of oral fluconazole (150 mg, administered once daily every 3 days) during the acute phase. Those who had culture-confirmed vulvovaginal candidiasis from the screening sample and achieved substantial resolution of signs and symptoms entered the maintenance phase.

In the maintenance phase, patients were randomly assigned to receive oral ibrexafungerp 300 mg (n=130) or placebo (n=130). Treatment was administered twice daily for 1 day and repeated once every 4 weeks for a total of six treatments. The primary endpoint was clinical success, and the secondary endpoint was the absence of mycological recurrence, both assessed at week 24.

As for the other endpoints, rescue antifungal medication was given in 31.5 percent of patients in the ibrexafungerp group and 41.5 percent in the placebo group by week 24. The rates of mycological eradication ranged from 63.8 percent to 66.2 percent in the ibrexafungerp group and from 56.2 percent to 59.2 percent in the placebo group by weeks 12, 24, and 36.

“Future studies could investigate whether other dose regimens with ibrexafungerp could result in higher cure rates and how this compares to azole-based therapies,” the authors said.