Oteseconazole proves safe, effective against recurrent vulvovaginal candidiasis
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Oteseconazole, an investigational oral antifungal therapy, was shown to be safe and effective in the treatment of acute and recurrent vulvovaginal candidiasis, according to a study presented during IDWeek.
“About 75% of all adult women experience at least one episode in their lifetime,” Mark G. Martens, MD, an OB/GYN professor at Drexel University College of Medicine and vice president and chief academic officer at Tower Health, said during the presentation. “Approximately 6% to 9% of all women develop recurrent vulvovaginal candidiasis.”
Most cases historically have been caused by Candida albicans, but infections caused by non-albicans species are increasing in prevalence, Martens said, and non-albicans species of Candida are associated with a higher frequency of recurrent infections.
The researchers defined recurrent vulvovaginal candidiasis as three episodes or more of acute candidiasis per year, with symptoms including itching, burning and abnormal discharge. Typical treatment involves addressing the acute episode, followed by long-term suppressive therapy with weekly or biweekly oral fluconazole.
“However, upon cessation of therapy, over 50% of patients with recurrent vaginal candidiasis experience an infection within the next 6 months,” Martens said. “While the physical symptoms are distressing, the emotional and psychological consequences of a recurrent infection and impact on your daily life can really take a toll.”
Meanwhile, fluconazole comes with safety liabilities limiting chronic dosing, such as liver toxicity, drug-to-drug interactions and increased risks for miscarriage and birth defects when used while pregnant. Emerging C. albicans azole resistance and poor azole activity against Candida glabrata and Candida krusei are concerns as well, Martens said.
But oteseconazole, a fungal CYP-51 inhibitor, offers high potency against fluconazole-resistant Candida species and 2,000 times more selectivity than fluconazole in addition to robust pharmacokinetics and long half-life for sustained efficacy, according to the researchers. More than 1,800 participants have been dosed to date, indicating its strong safety profile.
The randomized, double-blind, phase 3 study — called ultraVIOLET — compared oteseconazole to fluconazole and placebo among 219 participants aged 12 years and older with two or more episodes of acute vulvovaginal candidiasis in the previous 12 months.
Participants who presented with a vulvovaginal signs and symptoms score of at least 3 and tested positive for Candida were randomly assigned to receive oteseconazole (four 150 mg capsules on day 1 followed by three 150 mg capsules on day 2) or fluconazole (three sequential 150 mg doses every 72 hours), both with matching placebo capsules.
Those whose scores dropped below 3 by day 14 next moved into a maintenance phase and received oteseconazole or placebo weekly for 11 weeks. Participants were followed up through week 50.
By day 14, 93.2% of patients on oteseconazole and 95.8% of patients on fluconazole saw their acute vulvovaginal candidiasis episode resolved — meeting the criteria for noninferiority. But oteseconazole was shown to be statistically superior to fluconazole regarding the proportion of patients with one or more culture-verified acute vulvovaginal candidiasis episodes through week 50 in the intent-to-treat population — 42.2% of those in the fluconazole group vs. only 5.1% of participants in the oteseconazole group (P < .001).
According to the researchers, 54% of the patients on oteseconazole and 64% of the patients on fluconazole and placebo had at least one treatment-emergent adverse event, but most were deemed mild (25% of oteseconazole patients vs. 29% of fluconazole and placebo patients) or moderate (26% of oteseconazole patients vs. 31% of fluconazole and placebo patients). Additionally, there were no serious adverse events or adverse effects on liver function or QT intervals, according to the researchers.
The FDA has accepted a New Drug Application from Mycovia Pharmaceuticals, which is developing oteseconazole, for review, according to a company press release. In June, the FDA approved Scynexis’s novel 1-day oral treatment for vulvovaginal candidiasis, ibrexafungerp, making it the first approved drug in a novel antifungal class in more than 2 decades, the company said.
References:
Mycovia Pharmaceuticals Announces Presentations of its Supportive Phase 3 Clinical Study
(ultraVIOLET) Evaluating the Safety and Efficacy of Oteseconazole (VT-1161) for the
Treatment of Recurrent Vulvovaginal Candidiasis (RVVC) and Susceptibility Testing Against
Clinical Isolates at IDWeek 2021 Virtual Conference. https://static1.squarespace.com/static/5ab958c5e749401d7a2ed988/t/61547eb4a3ac21609b81d2b3/1632927412818/IDWeek+Release+FINAL_9.29.21.pdf. Published Sept. 29, 2021. Accessed Sept. 30, 2021.
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Martens MG, et al. Abstract 107. Presented at: IDWeek; Sept. 29-Oct. 1, 2021 (virtual meeting).
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