Highlights
Brexafemme (ibrexafungerp) is a new drug indicated for the treatment of adult and post-menarchal pediatric females with vulvovaginal candidiasis
Oral Brexafemme, approved by the U.S. Food and Drug Administration (FDA) in early June 2021, was developed by Scynexis.
Ibrexafungerp is the first member of a new class of antifungal drugs in more than 20 years.
The treatment of vulvovaginal candidiasis with Brexafemme lasts only one day.
What Is Vulvovaginal Candidiasis
Vulvovaginal candidiasis, also known as vaginal yeast infection, is a common cause of vulvovaginitis due to the growth of Candida albicans and other Candida fungi. Approximately 75% of women experience at least one case of this condition.
Vulvovaginal candidiasis can be idiopathic or secondary to other risk factors, including antibiotic use, sexual intercourse, pregnancy, oral contraceptives, and diabetes mellitus.
Typical symptoms of vaginal yeast infection include thick white vaginal discharge, often accompanied by vulval itching and irritation, external dysuria, and/or dyspareunia.
C. albicans accounts for 85%–95% of vaginal yeast strains.
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Recurrent vulvovaginal candidiasis is defined as more than 3–4 documented symptomatic separate episodes within 1 year. Recurrent disease is encountered in up to 9% of patients.
Uncomplicated vulvovaginal candidiasis is treated with antifungal drugs: either azole antimycotics (oral fluconazole or intravaginal clotrimazole, miconazole, tioconazole, butoconazole, or terconazole) or the polyene antimycotic nystatin intravaginally.
Treatment of complicated vulvovaginal candidiasis (severe or recurrent disease; infection caused by Candida species other than C. albicans; infection in pathological conditions) involves identifying the relevant pathogen and determining its sensitivity to pharmacotherapy. The latter, being prolonged in treatment time, may include oral fluconazole, intravaginal boric acid, nystatin or flucytosine (together with amphotericin B), as well as itraconazole, posaconazole, voriconazole, anidulafungin, caspofungin, micafungin.
Vivjoa (oteseconazole), developed by Mycovia Pharmaceuticals, is the first drug approved by FDA specifically to treat recurrent vaginal yeast infection.
Vivjoa: First Drug for Chronic Vaginal Yeast Infection
Oteseconazole by Mycovia Pharmaceuticals will prevent the risk of recurrent episodes of vulvovaginal candidiasis.
Brexafemme: Mechanism of Action of Ibrexafungerp
Ibrexafungerp (SCY-078) is an oral small-molecule drug compound belonging to the triterpenoids and acting as a semi-synthetic derivative of enfumafungin. Ibrexafungerp inhibits glucan synthase, an enzyme involved in the formation of 1,3-β-D-glucan, a key component of the fungal cell wall not present in mammalian cells. This leads to the suppression of resistance against osmotic forces, which results in cell lysis.
Although the mechanism of action of ibrexafungerp is similar to that of the echinocandins (anidulafungin, caspofungin, micafungin), the molecule is structurally different and interacts differently with its target. Ibrexafungerp retains activity against most strains resistant to echinocandins due to point mutations in the FKS1 and FKS2 genes.
Ibrexafungerp is the first representative of a new family of compounds called fungerps.
Ibrexafungerp is characterized by its concentration-dependent fungicidal activity against Candida fungi. Ibrexafungerp exhibits in vitro and in vivo activity against Candida albicans. Ibrexafungerp works in vitro against most isolates of the following microorganisms: Candida auris, Candida dubliniensis, Candida glabrata, Candida guilliermondii, Candida keyfr, Candida krusei, Candida lusitaniae, Candida parapsilosis, Candida tropicalis, and Aspergillus species. Ibrexafungerp, like echinocandins, lacks significant activity against pathogens causing mucormycosis, although it shows some action against historically difficult to eradicate Lomentospora prolificans and Paecilomyces variotii.
Possible resistance to ibrexafungerp, evaluated in vitro, is associated with mutations in the FKS2 gene. Ibrexafungerp retains activity against most fluconazole-resistant Candida species.
Brexafemme: Efficacy and Safety of Ibrexafungerp in Vulvovaginal Candidiasis Treatment
The efficacy of Brexafemme was evaluated in the equally designed VANISH 303 (NCT03734991) and VANISH 306 (NCT03987620) clinical trials phase 3 (randomized, double-blind, placebo-controlled, multicenter) involving patients (n=568) with acute vulvovaginal candidiasis.
Ibrexafungerp was administered orally one day in two doses of 300 mg with 12 hours between them.
The primary endpoint, stated clinical cure (complete resolution of signs and symptoms of the disease) between 8 and 14 days after completion of treatment, was 50.0% and 63.5% of patients in the ibrexafungerp groups — versus 28.0% and 44.9% in the placebo groups (p=0.001 and p=0.009).
Among the secondary endpoints:
- Mycological eradication (culture with no growth of Candida species) after 8–14 days: in 49.5% and 58.7% of patients in the ibrexafungerp groups — vs. 19.0% and 29.2% in the control groups (p<0.001).
- Clinical cure after 25 days: 59.5% and 72.5% — vs. 44.0% and 49.4% (p=0.007 and p=0.006).
The most common adverse reactions to Brexapheme administration were diarrhea (16.7% of subjects — versus 3.3% in the placebo groups), nausea (11.9% vs. 4.0%), abdominal pain (11.4% vs. 5.1%), dizziness (3.3% vs. 2.5%), vomiting (2.0% vs. 0.7%).
Ibrexafungerp: What’s Next
Scynexis continues the development of ibrexafungerp (oral and intravenous), focusing it on the prevention of recurrent vulvovaginal candidiasis as well as the treatment of invasive pulmonary aspergillosis (in combination with voriconazole) and invasive candidiasis refractory or intolerant to standard antifungal therapy. The latter include: mucocutaneous candidiasis, coccidioidomycosis (Valley fever), histoplasmosis, blastomycosis, chronic pulmonary aspergillosis, allergic bronchopulmonary aspergillosis, invasive pulmonary aspergillosis, recurrent vulvovaginal candidiasis, candidemia.
Extras
Brexafemme (ibrexafungerp). Prescribing information. U.S. [PDF]
Scynexis. Investor presentation. January 2022. [PDF]
Scynexis. Hospital pipeline update, December 6, 2021. [PDF]
Scynexis. Brexafemme for the treatment of VVC. Commercial update call. June 29, 2021. [PDF]
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Ibrexafungerp: A novel oral triterpenoid antifungal in development for the treatment of Candida auris infections. Antibiotics (Basel). 2020 Aug 25;9(9):539. [source]
Ibrexafungerp: A novel oral glucan synthase inhibitor. Med Mycol. 2020 Jul 1;58(5):579-592. [source]
Combination therapy with ibrexafungerp (formerly SCY-078), a first-in-class triterpenoid inhibitor of (1→3)-β-d-glucan synthesis, and isavuconazole for treatment of experimental invasive pulmonary aspergillosis. Antimicrob Agents Chemother. 2020 Jun; 64(6): e02429-19. [source]
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