Novel antifungal treatment approved for vaginal candidiasis

Efficacy

Two randomized placebo-controlled clinical trials evaluated the safety and efficacy of ibrexafungerp. Eligible participants in both trials were post-menarche, nonpregnant females diagnosed with VVC. Signs and symptoms of VVC include erythema, excoriation, edema, irritation, burning, and itching. In trials, a diagnosis of VVC is defined as a minimum composite vulvovaginal signs and symptoms (VSS) score greater than or equal to 4 and a minimum of 2 moderate signs or symptoms (score of 2 or greater), positive microscopic examination in a sample demonstrating yeast, and a normal vaginal pH. Signs and symptoms were scored along a 4 point scale: 0 (absent) to 3 (severe). Median VSS scores at baseline in trials 1 and 2 were 9 and 10, respectively, at baseline; range 4 to 18. In both trials, the majority of cultures were positive for Candida albicans. Enrolled participants received two 150-mg tablets (300-mg dose) of ibrexafungerp or placebo 12 hours apart in a single day, a total daily dose of 600 mg. Participants were reassessed at a test-of-cure (TOC) visit between days 8 to 14 and a follow-up visit between days 21 to 29. Participants with a positive culture for Candida who received at least 1 dose of the study drug were included in a modified intention to treat analysis (MITT).Compared with placebo, a greater percentage of participants on ibrexafungerp demonstrated negative cultures at the TOC visit (P < .001) and VSS scores of 0 (ie, complete clinical response) at the TOC (P = .001 and .009) and follow-up visits (P = .007 and.006).

Safety

In trials, a total of 545 participants were exposed to a dose of ibrexafungerp. The most common adverse effects (AEs) noted in participants administered ibrexafungerp are diarrhea (16.7%), nausea (11.9%), abdominal pain (11.4%), dizziness (3.3%), and vomiting (2.0%). For comparison, the most common AE noted in participants administered placebo in trials is abdominal pain (5.1%). Ibrexafungerp is metabolized by cytochrome P450 (CYP3A). Concomitant administration of strong inhibitors or moderate to strong inducers of CYP3A may alter the patient’s exposure to ibrexafungerp. A reduced dose of ibrexafungerp, 150mg (1 tablet), should be given when concomitantly administered with strong CYP3A inhibitors. Ibrexafungerp is potentially teratogenic. The use of ibrexafungerp is contraindicated in pregnant women. A patient’s pregnancy status should be confirmed prior to use. The manufacturer recommends the use of contraception for 4 days after the last dose of ibrexafungerp for all women of reproductive potential. If a woman is pregnant or pregnancy is detected within 4 days after the last dose of ibrexafungerp, patients should report the pregnancy to the manufacturer to include in an ongoing safety analysis by calling 1-888-982-7299.

Dosing

The recommended dosage of ibrexafungerp for treatment of VVC is 300 mg. This dose is provided as two 150-mg tablets. To complete a full course of therapy, patients should take two 150-mg tablets for the first dose and two 150-mg tablets 12 hours later. This medication may be taken with or without food.

Reference

Brexafemme. Prescribing Information. Scynexis, Inc; 2021. Accessed June 14, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214900s000lbl.pdf