16 May ibrexafungerp: First New Drug for Vaginal Yeast Infections Shows Promise
MedicalResearch.com Interview with:
Marco Taglietti, M.D.
President and Chief Executive Officer
Dr. Taglietti discusses SCYNEXIS’ announcement of positive results from its second Phase 3 study investigating the safety and efficacy of oral ibrexafungerp as a treatment for vaginal yeast infection.
MedicalResearch.com: What is the background for this study?
Response: The VANISH-306 study is one of two Phase 3 randomized, double-blind, placebo-controlled, multi-center studies designed to demonstrate the superiority of oral ibrexafungerp to placebo as a treatment of vaginal yeast infections, also known as vulvovaginal candidiasis. Ibrexafungerp is a novel oral/intraveneous broad-spectrum antifungal in late stage development for multiple indications, from the treatment and prevention of vaginal yeast infections to life-threatening invasive fungal infections in the hospital setting.
The VANISH-306 study was conducted in 42 centers in the US and EU and enrolled 449 patients. Patients were randomized to oral ibrexafungerp (two doses of 300mg taken 12 hours apart for one day) or placebo in a 2:1 ratio The primary endpoints included clinical cure rate, defined as the complete resolution of all signs and symptoms at the test-of-cure visit (Day-10) and secondary endpoints included mycological eradication and change in signs and symptoms scores compared to baseline at both day 10 and follow-up visit (Day-25). The VANISH-306 study reported positive topline data which showed that 63.3% of ibrexafungerp-treated patients saw a complete resolution of signs and symptoms 10 days following a single day dose of ibrexafungerp.
The first study in the VANISH program was VANISH-303, a US-based study, had an identical design to the VANISH-306 study. The VANISH-303 study reported positive topline data in November 2019 which showed that 50.5% of ibrexafungerp-treated patients saw a complete resolution of signs and symptoms 10 days following a single day dose of ibrexafungerp.
Both VANISH studies showed a highly significant statistical difference in the primary and secondary efficacy endpoints. The product was well tolerated.
MedicalResearch.com: How common is vaginal yeast infection and recurrent infection?
Response: Vaginal yeast infections affect up to three out of four women in their lifetime and primarily affect women of childbearing ages. Recurrent vaginal yeast infections, defined as more than three episodes in a 12-month period, affect 8-10% of all VVC women. Despite the prevalence of these conditions, there is currently only a single oral antifungal available for the treatment of vaginal yeast infections, and there is no approved treatment for the prevention of recurrent vaginal yeast infections. OTC topical agents and the one oral prescription have multiple limitations both in terms of activity and safety.
MedicalResearch.com: How does ibrexafungerp differ from other treatments for vaginal yeast infection?
Response: Currently, fluconaxzole is the only one orally available antifungal for the treatment of vaginal yeast infections. However, fluconazole is not a one size fits all medication, and has some meaningful limitations.
Fluconazole is known to have safety gaps such as embryo/fetal toxicities, QTC prolongation, liver toxicity and, importantly, may cause negative interactions with other drugs. So far in its development, the experimental drug ibrexafungerp has not shown any major systemic safety signals, nor any evidence of embryo/fetal toxicity in animal studies. In addition, Phase 1 studies have shown limited risk of potential for drug-drug interactions.
One major distinction is in the mechanism of action. Fluconazole, like all azole agents, is fungistatic, which means it only slows fungal growth, whereas ibrexafungerp is fungicidal, which means it actually kills the pathogen. Additionally, ibrexafungerp has shown to date relevant attributes for treatmnent of vaginal yeast infections such as, enhanced activity at low vaginal pH, broad spectrum activity including fluconazole-resistant Candida strains and high vaginal tissue penetration. If approved, we believe that the cumulative advantages of ibrexafungerp could make it a valuable treatment option for patients not currently satisfied with existing therapies. It would also provide a much-needed alternative for physicians, often frustrated with the limitations of fluconazole and and other topical treatments. We look forward to the results from the ongoing Phase 3 CANDLE study evaluating oral ibrexafungerp for the prevention of recurrent vaginal yeast infections, for which there is currently no approved treatment.
MedicalResearch.com: What are the main findings of the Phase 3 finding?
Response: Our study found that 63.3% of ibrexafungerp-treated patients met the primary endpoint of clinical cure, defined as the complete resolution of signs and symptoms 10 days following a single day dose and that 72.3% of patients showed a significant clinical improvement of signs and symptoms at Day-10. In addition, at the Day-25 follow-up, 73.9% of ibrexafungerp-treated patients had a complete symptom resolution, showing the potential sustained effect of ibrexafungerp in VVC patients..
MedicalResearch.com: What side effects if any have been seen?
Response: In the VANISH-306 study, ibrexafungerp was generally safe and well-tolerated. Severe and serious adverse events (AEs and SAEs) were rare and there were no drug-related SAEs. Similar to previous studies, including our Phase 3 VANISH-303 and our Phase 2 DOVE study in VVC patients, the majority of Treatment-Emergent AEs (TEAEs) were gastrointestinal (GI) in nature, with the three most common GI events (diarrhea/loose stool, nausea and abdominal pain) occurring at rates of 9.4%, 8.4% and 2.7%, respectively.
MedicalResearch.com: What should readers take away from your report?
Response: The cumulative results of this study suggest that oral ibrexafungerp has the potential to provide a much-needed alternative to current treatment options for patients with vaginal yeast infections who are not responsive to, or satisfied with, current treatment options. We know there is a great need for new options which was evident when we completed enrollment approx. 4 months ahead of schedule, in both VANISH studies. Based on the positive findings from our VANISH program, we plan to file a new drug application for the use of ibrexafungerp for the treatment of vaginal yeast infections in the second half of this year and look forward to the results of our ongoing Phase 3 CANDLE study evaluating ibrexafungerp for the prevention of recurrent vaginal yeast infections in 2021.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: We also have multiple ongoing late-stage clinical trials exploring the use of oral ibrexafungerp for the treatment of life-threatening fungal infections, including one dedicated trial for infections caused by the emerging fungal pathogen, Candida auris. C. auris was first identified in 2009 and has since spread across the globe with a mortality rate of 30-60%. C. auris is difficult to identify, is commonly resistant to current antifungals and can spread rapidly in a hospital setting, making it particularly dangerous for patients with a compromised immune system, such as those receiving treatment for cancer or organ transplants.
Ibrexafungerp has been shown in multiple pre-clinical and clinical settings to be active against a broad range of pathogens, even against the most drug-resistant fungal strains. If approved, ibrexafungerp could be the first representative of new class of antifungals to enter the market in over 20 years. At SCYNEXIS, we believe that now more than ever, there is a growing need for innovation in the anti-infective field to combat the threat of evolving pathogens.
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