Patients with acute vulvovaginal candidiasis (VVC) greatly benefited from oral ibrexafungerp (Brexafemme, Scynexis), according to results of a global phase 3 randomized, double-blind, placebo-controlled superiority study published in the international journal of obstetrics and gynecology, BJOG.
Oral ibrexafungerp, which is a semisynthetic, triterpenoid derivative that blocks the synthesis of the fungal cell wall polymer beta-D-glucan, received approval from the U.S. Food and Drug Administration (FDA) in June 2021 and is available by prescription.
The study was conducted between June 2019 and February 2020 at 37 study sites: 19 in the U.S. and 18 in Bulgaria
The 449 female patients in total were all at least 12 years old with acute VVC and a vulvovaginal signs and symptoms (VSS) score of ≥4 at baseline.
Patients were randomly assigned 2:1 to 2 tablets of ibrexafungerp 150 mg or placebo, 2 times daily for 1 day only.
The primary endpoint was the percentage of patients with a clinical cure (VSS = 0) at the test-of-cure visit at mean day 11, for which ibrexafungerp showed a success rate of 63.3% versus 44.0% for placebo (P = 0.007).
Secondary endpoints included percentages of patients with mycological eradication; clinical cure and mycological eradication for overall success; clinical improvement of VSS ≤1 at test-of-cure visit; and complete resolution of symptoms at the follow-up visit at mean day 25.
Mycological eradication with ibrexafungerp was 58.5% compared to 29.8% with placebo (P < 0.001); overall success was 46.1% vs 28.4% (P = 0.022); and clinical improvement was 72.3% versus 54.8% (P = 0.01).
Symptom resolution was also sustained and further increased with ibrexafungerp than with placebo at follow-up: 73.9% vs. 52.4%, respectively (P = 0.001).
The drug was generally well tolerated, with adverse events primarily gastrointestinal that were mild to moderate in severity.
“We were pleased to see that this medication was highly effective in treatment of women with acute [VVC],” said Ryan Sobel, MD, a clinical assistant professor of ob/gyn at Sidney Kimmel Medical College at Thomas Jefferson University in Philadelphia, Pennsylvania, who is one of the principal investigators in the U.S.
“Ibrexafungerp is a promising novel, well-tolerated and effective oral 1-day treatment for acute VVC,” said Sobel, noting that the first-in-class medication results in an unstable cell wall and the subsequent death of the yeast.
Still, the results of the study “should not and cannot be compared to prior studies using different medications and protocols,” Sobel told Contemporary OB/GYN®.
Nonetheless, for the first time in nearly 2 decades, there is a new orally available antifungal to treat acute VVC, according to Sobel, an attending physician and co-director of the Jefferson Vulvovaginal Health Center in Philadelphia. “For women who are not able to use fluconazole -- which is the only available oral alternative—due to a variety of reasons, such as side effects, allergy and fungal resistance, ibrexafungerp represents a convenient, safe and effective treatment,” he said.
Currently, however, the drug is contraindicated in pregnancy until further data is available. “Also, being a newly patented medication, it is not yet covered by insurance providers, so the cost can be high and may be use-prohibitive for some patients,” Sobel said.
Sobel is a consultant and is on the advisory board and speakers bureau for Scynexis.