The First Phase III Project Of Oral Non-azole Antifungal Drug Ibrexafungerp To Treat Vulvovaginal Candidiasis Is Successful

- Mar 17, 2020-

Scynexis is a biotechnology company headquartered in New Jersey, USA, focused on developing innovative therapies to overcome and prevent infections that are difficult to treat and resistant to. Recently, the company announced the positive top-line results of the new broad-spectrum antifungal drug ibrexafungerp phase III VANISH-306 study.


This study investigated the efficacy and safety of oral ibrexafungerp in the treatment of vulvovaginal candidiasis (VVC). The results show that ibrexafungerp has a high statistical advantage, safety, and tolerability in terms of primary and critical secondary endpoints compared to placebo. The positive results of this study are consistent with the previously reported Phase III VANISH-303 study. The primary and critical secondary endpoints in these two VANISH key trials are required for regulatory approval of VVC indications, and the study data paved the way for the submission of regulatory application documents for ibrexafungerp treatment of VVC in the second half of 2020.


ibrexafungerp is a new, broad-spectrum antifungal drug and the first representative of triterpenoids, a unique structure of glucan synthase inhibitors. ibrexafungerp combines the good activity of glucan synthase inhibitors with the potential flexibility of oral and intravenous administration. Currently, the drug is being developed to treat fungal infections caused by Candida (including Candida auris, C. auris) and Aspergillus. In vitro and in vivo studies, the drug showed broad-spectrum antifungal activity against a variety of drug-resistant pathogens (including strains resistant to azole and echinocandins).


The announcement of the results of the VANISH-306 research topline marks the successful completion of the VANISH Phase III project. Scynexis plans to submit a new drug application (NDA) to the US Food and Drug Administration (FDA) later this year. If approved, ibrexafungerp will be the first and only oral non-azole drug used to treat vaginal yeast infections. Vaginal yeast infection is a disease that can affect up to three-quarters of women in a lifetime, but treatment options are limited and no new treatment has been approved for more than 20 years. The positive results of the VANISH project show that ibrexafungerp has the potential to solve vaginal yeast infections of a wide range of disease severity. The drug will be an ideal treatment option, especially for patients who are currently dissatisfied with existing therapies.


David Angulo, MD, Chief Medical Officer of Scynexis, said: "We are excited about the results from VANISH-306, which is consistent with the previously reported VANISH-303 study, supporting the efficacy of oral ibrexafungerp as a new treatment for vaginal yeast infections And safety. Two VANISH phase III studies also confirmed the sustained clinical effect of ibrexafungerp during 25 days of follow-up, which is consistent with the results of the phase IIb DOVE study. At the same time, we are continuing to advance the CANDLE phase III study to test oral ibrexafungerp prevention Recurrent vaginal yeast infection (there is currently no approved treatment) and it is expected to report the latest data for this indication in the second half of 2021. "

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Vulvovaginal candidiasis (VVC), commonly known as vaginal yeast infection caused by Candida, is the second most common cause of vaginitis. Although these infections are usually caused by Candida albicans, fluconazole-resistant Candida strains, such as Candida glabrata, have been reported to be increasingly common. VVC can cause severe morbidity, including severe genital discomfort, decreased sexual pleasure, psychological distress, and loss of productivity. Typical symptoms of VVC include itching, vaginal soreness, irritation, loss of vaginal mucosa, and abnormal vaginal secretions.


It is estimated that 70-75% of women worldwide will have at least one episode of VVC in their lifetime, and 40-50% of women will experience two or more episodes of VVC. About 6-8% of patients with VVC have recurrent disease, defined as experiencing at least three episodes in 12 months.


At present, the treatment of VVC includes several topical azole antifungal drugs (clotrimazole, miconazole, etc.) and fluconazole, the latter is currently the only oral antifungal drug approved for the treatment of VVC in the United States. Fluconazole reported a 55% cure rate on its label and now includes warnings of potential fetal harm, indicating the need for new oral alternatives. Oral fluconazole or topical drugs cannot fully meet the needs of female patients with moderate to severe VVC, repeated VVC, VVC caused by Candida anti-fluconazole, and VVC of childbearing age. In addition, there are no oral replacements for fluoroconazole patients who do not respond or tolerate VVC treatment, nor are there FDA-approved products to prevent relapsed VVC.


ibrexafungerp is a new, broad-spectrum antifungal drug and the first representative of triterpenoids, a unique structure of glucan synthase inhibitors. ibrexafungerp combines the good activity of glucan synthase inhibitors with the potential flexibility of oral and intravenous administration. Currently, the drug is being developed to treat fungal infections caused by Candida (including Candida auris, C. auris) and Aspergillus. In vitro and in vivo studies, the drug showed broad-spectrum antifungal activity against a variety of drug-resistant pathogens (including strains resistant to azole and echinocandins). Previously, the US FDA has granted ibrexafungerp oral and intravenous preparations for the treatment of invasive candidiasis (IC, including candidemia), invasive aspergillosis (IA), and vulvovaginal candidiasis (VVC). QIDP) and Fast Track Qualification (FTD), and granted Orphan Drug Qualification (ODD) for the treatment of IC and IA indications. ibrexafungerp was previously called SCY-078.


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Results of the VANISH-306 study: (1) 63.3% of ibrexafungerp-treated patients reached the primary end point of clinical cure at the 10th day of the test-of-cure (TOC) visit. Clinical cure was defined as a single day After the 600 mg dose regimen (two doses of 300 mg taken 12 hours apart), all vaginal signs and symptoms (S & S) completely disappeared. (2) 58.5% of ibrexafungerp-treated patients reached the secondary end point of fungal eradication at the TOC visit, that is, negative culture. (3) 72.3% of ibrexafungerp-treated patients were classified as clinically improved at the TOC visit, defined as a total sign and symptom score of 0 or 1. (4) 73.9% of patients completely disappeared on the 25th day of the visit.


Safety results: In the VANISH-306 study, oral ibrexafungerp was generally safe and well tolerated. Serious adverse events (SAE) are rare and there are no drug-related SAEs. Similar to previous studies, most of the treatment-induced adverse events (TEAE) that occurred at a higher frequency in the ibrexafungerp treatment group observed in the VANISH-306 study were essentially gastrointestinal (GI) events, of which three The most common gastrointestinal events (diarrhea / faeces, nausea, abdominal pain) were 9.4%, 8.4%, and 2.7%, respectively. Most of these events were mild, of short duration, and did not lead to discontinuation, which confirmed the well-tolerated previously observed single-day 600 mg oral ibrexafungerp regimen.


The joint safety database of VVC patients in the VANISH and DOVE projects currently includes more than 850 enrolled patients, of which 575 patients received a single daily 600mg ibrexafungerp treatment plan. In the total database, the total incidence of the most common gastrointestinal events in patients treated with ibrexafungerp was 16.7% for diarrhea / sparse stool, 11.8% for nausea, and 4.5% for abdominal pain. The data supports the good safety and tolerability of ibrexafungerp. (Bioon.com)