Clinical Pharmacology Update: Brexafemme From Scynexis, Inc

The FDA has approved ibrexafungerp oral tablets (Brexafemme; Scynexis, Inc) to treat adult and postmenarchal pediatric female patients with vulvo- vaginal candidiasis (VVC).¹

Symptoms of VVC include abnormal vaginal discharge, excoriation of vaginal mucosa, irritation, pruritus, and vaginal soreness. Approximately 70% to 75% of women worldwide will experience 1 VVC episode in their lifetime, and 40% to 50% of these women will have multiple episodes. Candida albicans

is frequently the cause of VVC, but an increase in fluconazole-resistant and non-albicans Candida strains, such as Candida glabrata, has been observed. Brexafemme is the first novel antifungal to be approved for VVC in over 20 years, and it is the only nonazole and oral treatment available.²

PHARMACOLOGY AND PHARMACOKINETICS

Brexafemme is a triterpenoid antifungal agent that displays concentration-dependent fungicidal activity against Candida species. It inhibits glucan synthase, which is an enzyme involved in the formation of 1,3--D-glucan and an essential component of the fungal cell wall.

Brexafemme reaches maximum plasma concentrations 4 to 6 hours after multiple and single oral dosing. It displays an elimination half-life of approximately 20 hours. Brexafemme is a substrate of cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp). In vitro, Brexafemme is an inhibitor of CYP2C8, CYP3A4, OATP1B3 transporter, and P-gp transporter. It is not a CYP3A4 inducer.¹

DOSING AND ADMINISTRATION

The dose of Brexafemme is 300 mg twice a day for 1 day, for a total treatment dose of 600 mg. The medication may be taken

with or without food. Female patients of reproductive potential should have their pregnancy status verified before beginning treatment. Brexafemme is supplied as 150-mg tablets.¹

CLINICAL TRIALS

The efficacy and safety of Brexafemme for the treatment of VVC were evaluated in 2 double-blind, multicenter, placebo-controlled, randomized trials of nonpregnant post-menarchal female participants with a diagnosis of VVC. The VVC diagnosis was defined as a composite vulvovaginal signs and symptoms (VSS) score of greater than or equal to 4 with at least 2 signs or symptoms having a score of 2 or greater, a normal vaginal pH, and a positive microscopic examination revealing budding yeasts or yeast forms. The total composite VSS score was based on the signs of edema, erythema, and excoriation, and the symptoms of burning, irritation or itching. Each component was scored as 0 for absent, 1 for mild, 2 for moderate, or 3 for severe. In trial 1, the baseline median VSS score was 9, and 92% of participants were culture positive with C albicans. In trial 2, the baseline median VSS score was 10, and 89% of participants were culture positive with C albicans. Participants in both trials were randomized to receive either Brexafemme or a placebo. Study visits included the test of cure (TOC) visit 8 to 14 days after administration and a follow-up visit 21 to 29 days after administration.

Efficacy was evaluated at the TOC visit. A complete clinical response was defined as the total resolution of signs and symptoms, as determined by a VSS score of 0. Other end points included a negative culture for Candida species at the TOC visit and the clinical outcome at the follow-up visit. The trials found statistically significantly greater percentages of participants who received Brexafemme experienced a complete clinical response at the TOC visit, a negative culture at the TOC visit, and a complete clinical response at the follow-up visit.^1,2

CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS

Treatment with Brexafemme is con- traindicated in pregnancy and in patients with a hypersensitivity to the medication.

Based on animal reproduction studies, the use of Brexafemme in preg- nancy may cause fetal harm. Female patients of reproductive potential should use effective contraception during treatment with Brexafemme and for 4 days after the last dose. When used concomitantly with a strong CYP3A inhibitor, the exposure of Brexafemme is increased, and the dose of Brexafemme should be reduced to 150 mg twice daily for 1 day. Brexafemme should not be used concomitantly with a moderate or strong CYP3A inducer, as this combination may significantly reduce the exposure of Brexafemme.

The most frequent adverse reactions are abdominal pain, diarrhea, dizziness, nausea, and vomiting.¹

Monica Holmberg, PharmD, BCPS, is a pharmacist and Pharmacy Times® contributor.

REFERENCES

1. Brexafemme. Prescribing information. Scynexis Inc; 2021. Accessed August 4, 2021. https://d1io3yog0oux5.cloudfront.net/scynexis/files/pages/scynexis/db/pis/Digital+Ibrexafungerp+Prescribing+Information+%28PI%29.pdf
2. Scynexis announces FDA approval of Brexafemme (ibrexafungerp tablets) as the first and only oral non-azole treatment for vaginal yeast infections. News release. Scynexis Inc; June 2, 2021. Accessed August 4, 2021. https://www.scynexis.com/news-media/press-releases/detail/240/scynexis-announc- es-fda-approval-of-brexafemme