Scynexis reports positive results from first phase III (VANISH-303) registration study of oral ibrexafungerp in vulvovaginal candidiasis .

Scynexis, Inc. announced positive top-line results for its Phase III VANISH-303 study investigating the safety and efficacy of oral ibrexafungerp as a treatment for women with vulvovaginal candidiasis (VVC). Specifically, ibrexafungerp achieved superiority over placebo at a highly statistically significant level (p?0.001) for the primary endpoint and key study endpoints required for regulatory approval of the VVC indication. These top-line results come earlier than originally anticipated due to faster-than-expected enrollment in VANISH-303 and support the Company's stated timeline to submit a New Drug Application (NDA) to the FDA for the treatment of VVC in the second half of 2020.

These results confirm the clinical benefits and favorable tolerability profile observed in the Phase IIb DOVE study, strengthening confidence in ibrexafungerp's future regulatory and commercial success. Ibrexafungerp is the first molecule in an entirely new class of antifungals and possesses key attributes relevant to the VVC indication, including fungicidal activity against Candida. The company believes that ibrexafungerp, as a novel, non-azole, oral therapy, can address large unmet medical needs for women with VVC who may not respond to fluconazole, the only oral option currently available, which is fungistatic against Candida and also has well-documented concerns around drug-drug interactions and embryo-fetal toxicity for women of childbearing age.

The VANISH-303 study was designed following the 2016 "Vulvovaginal Candidiasis: Developing Drugs for Treatment, Guidance for Industry" by the FDA. The study was conducted at 28 centers in the U.S. and enrolled 376 patients randomized to oral ibrexafungerp (single-day 600mg dose regimen consisting of two doses of 300mg administered 12 hours apart) or matching placebo in a 2:1 ratio. To be eligible for this study, patients needed to present with an acute episode of VVC with a signs and symptoms (S&S) score of four or greater on a scale of zero (no S&S) to 18 (maximum severity). Primary efficacy analyses were conducted in the modified-intent-to-treat (mITT) population, comprised of patients with culture confirmed Candida spp. infection at baseline who received at least one dose of study treatment. The characteristics for both groups were evenly balanced at baseline, including the severity of the vaginal infection.

Ibrexafungerp achieved highly statistically significant superiority over placebo (p?0.001) for the primary endpoint and key study endpoints required for regulatory approval . The primary endpoint required for registration is clinical cure, defined as complete resolution (score of 0) of all S&S at the Day-10 test-of-cure (TOC) visit. The observed clinical cure for ibrexafungerp was 50.5%, showing highly statistically significant superiority to placebo (p=0.001). Mycological eradication (secondary endpoint) at TOC in ibrexafungerp patients was 49.5%, also showing superiority to placebo (p<0.001). the vanish-303 ibrexafungerp efficacy results confirm results observed in the phase iib dove study and achieve the superiority versus placebo required for regulatory approval.>

Clinical improvement (score of 0 or 1) at TOC , another secondary endpoint which is a clinically relevant assessment of treatment response, was achieved in 64.4% of ibrexafungerp patients (p<0.001 against placebo. this result is also consistent with findings observed in the phase iib dove study.> Safety and tolerability : Oral ibrexafungerp was generally safe and well tolerated. Severe and serious adverse events (AEs) were rare, with more cases reported in the placebo group than the ibrexafungerp group, and there were no drug-related serious AEs. The majority of Treatment-Emergent AEs (TEAEs) observed at a higher frequency in the ibrexafungerp group were gastrointestinal in nature, with the three most common GI events (diarrhea/loose stool, nausea and abdominal pain) occurring at rates of 25.5%, 16.6% and 7.3%, respectively, similar to the rates seen in the Phase 2b DOVE study. These events were predominantly regarded as mild, of short duration and did not lead to discontinuation, confirming the favorable tolerability profile of the single-day 600mg dose regimen of oral ibrexafungerp previously observed.Only top-line data has been reported to date and comprehensive analysis of the totality of the data is still ongoing.

A second global Phase III study (VANISH-306), with identical design, is being conducted in the U.S. and Europe. Enrollment continues to progress rapidly, and the Company anticipates top-line data early in the second quarter of 2020. More information about this study can be found at: NCT0398762. These two pivotal studies are expected to provide the safety and efficacy data to support an NDA for ibrexafungerp for the treatment of VVC, with submission to the FDA planned in the second half of 2020.

Additionally, enrollment is ongoing in the CANDLE study , a global Phase III, randomized, double-blind, placebo-controlled trial designed to evaluate the safety and efficacy of oral ibrexafungerp (300mg BID for one day, given once per month for a total of six treatment days) compared to placebo in female patients with recurrent VVC. This study is being conducted at approximately 50 global sites and is expected to enroll approximately 320 patients. This study also has an open-label sub-study evaluating oral ibrexafungerp (single-day 600mg dose regimen) for the treatment of patients not responding to oral fluconazole. The Company expects to file a supplemental NDA for oral ibrexafungerp for the prevention of recurrent VVC in 2021. The Company believes this study, combined with the ongoing VANISH Phase III program, will provide ibrexafungerp with the broadest label of any VVC therapy, addressing both treatment of acute episodes and prevention of recurrence. More information about the CANDLE study can be found at: NCT04029116.