By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
The FDA has approved the first-in-class triterpenoid, or “fungerp,” a glucan synthase inhibitor, non-azole, antifungal agent to treat vulvovaginal candidiasis. The FDA classified the solution as a qualified infectious disease product and granted a fast track designation. This oral, one-day treatment course is distributed as Brexafemme.
INDICATIONS
Ibrexafungerp can be prescribed to treat adults and post-menarchal pediatric females with vulvovaginal candidiasis (VVC).1
DOSAGE
The recommended dose is 300 mg taken as two 150-mg tablets twice a day for one day.1 It may be taken without regard to meals. Because ibrexafungerp is metabolized by CYP3A, the dose should be reduced to one 150-mg tablet twice-daily with concomitant use of a strong CYP3A inhibitor (e.g., clarithromycin). Co-administration with CYP3A inducers is not recommended. Ibrexafungerp is available as a blister pack with four 150-mg tablets.
POTENTIAL ADVANTAGES
Ibrexafungerp, which interrupts fungal cell wall formation, demonstrated potent in vitro activity against Candida species, including certain echinocandin- and azole-resistant isolates.1,2 In contrast to azoles (e.g., fluconazole), which are fungistatic, ibrexafungerp is fungicidal at normal vaginal pH.1
POTENTIAL DISADVANTAGES
Based on animal studies, ibrexafungerp is contraindicated in pregnancy over risk of fetal harm.1 Pregnancy status should be verified in women of reproductive potential before initiation of treatment. An effective contraception should be used for four days after the last dose. The most frequently reported adverse reactions (> 10% vs. placebo) are diarrhea (16.7% vs. 3.3%), nausea (11.9% vs. 4.0%), and abdominal pain (11.4% vs. 5.1%).1
COMMENTS
The safety and efficacy of ibrexafungerp were evaluated in two randomized, placebo-controlled trials that included subjects with a VVC diagnosis.1 VVC was defined as a minimum composite vulvovaginal signs and symptoms (VSS) score of ≥ 4, positive microscopic evidence of yeast in a vaginal sample, and normal vaginal pH (≤ 4). The composite VSS score was based on vulvovaginal signs (erythema, edema, excoriation) and symptoms (itching, burning, or irritation). These are scored from 0 to 3 (absent, mild, moderate, or severe, respectively). The efficacy endpoint was complete clinical response (i.e., complete resolution of signs and symptoms [VSS score = 0]) at the test of cure (TOC) visit, day 8 to 14 after administration. Additional endpoints were negative Candida albicans culture at TOC and complete clinical response at follow-up (day 21 to day 29).
Subjects were randomized 2:1 to ibrexafungerp or placebo (n = 190 and n = 100 in trial 1 and n = 189 and n = 89 in trial 2). Complete clinical responses at TOC were 50.0% vs. 28.0% in trial 1 and 63.5% vs. 44.9% in trial 2. Negative culture rates were 49.5% vs. 19.0% and 58.7% vs. 29.2%, respectively. Complete clinical response rates at follow-up were 59.5% vs. 44.0% and 72.5% vs. 49.4%, respectively.
CLINICAL IMPLICATIONS
VVC or vaginal yeast infection is the second most common type of vaginal infection (after bacterial vaginal infections), affecting generally healthy women of child-bearing age.3,4 Typically, it is caused by an opportunistic fungus, Candida albicans. The Infectious Diseases Society of America recommends topical (intravaginal) or oral fluconazole treatment.5 Effectiveness is similar between vaginal products nightly for seven days and fluconazole as a single oral dose, and similar to those reported for ibrexafungerp.1,6 Ibrexafungerp may offer clinical advantage in non-albicans species (e.g., C. glabrata, C. auris) or refractory (azole-resistant) Candida albicans in VVC, but that remains to be established. Because of its good oral bioavailability (i.e., suitable for parenteral and oral administration) and in vitro activity, ibrexafungerp might play a role in the treatment of invasive candidiasis infections. The cost for ibrexafungerp is $475 for a treatment course vs. a course of generic fluconazole, which is less than $3.
REFERENCES
- Scynexis, Inc. Brexafemme prescribing information. June 2021.
- Davis MR, Donnelley MA, Thompson GR. Ibrexafungerp: A novel oral glucan synthase inhibitor. Med Mycol 2020;58:579-592.
- Centers for Disease Control and Prevention. Fungal diseases. Vaginal candidiasis. Page last reviewed Nov. 10, 2020.
- Willems HME, Ahmed SS, Liu J, et al. Vulvovaginal candidiasis: A current understanding and burning questions. J Fungi (Basel) 2020;6:27.
- Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 2016;62:e1-e50.
- Drugs.com. Diflucan. Last reviewed July 1, 2021.
Ibrexafungerp can be prescribed to treat adults and post-menarchal pediatric females with vulvovaginal candidiasis.
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