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SCYNEXIS reports Phase 2b data for SCY-078
JERSEY CITY, N.J—SCYNEXIS, Inc. has announced positive results from its Phase 2b dose-finding study (the DOVE study) evaluating oral SCY-078 for the treatment of vulvovaginal candidiasis (VVC). SCY-078, the first representative of a novel oral and intravenous triterpenoid antifungal family, is in clinical development for the treatment of multiple serious fungal infections, including VVC, invasive candidiasis (IC), invasive aspergillosis (IA) and refractory invasive fungal infections.
The DOVE study evaluated the safety and efficacy of five oral SCY-078 regimens, with total doses of SCY-078 ranging from 600mg to 1800mg and treatment durations of one or three days, compared to fluconazole (FLU), the standard of care for VVC. The study enrolled a total of 186 patients with moderate-to-severe acute VVC (composite signs and symptoms [S&S] score of seven or higher), with 153 patients in the culture-confirmed modified Intent-to-Treat (mITT) population who were assessed at the Day 10 Test-of-Cure (TOC) visit and at the Day 25 Follow-Up (FU) visit. Key efficacy parameters included clinical cure rate (primary endpoint) and mycological eradication; other efficacy evaluations included use of antifungal rescue therapy and changes of S&S score.
“The DOVE study accomplished its primary goal of identifying a well-tolerated oral dose regimen of SCY-078 with high clinical cure and mycological eradication rates,” said David Angulo, M.D., Chief Medical Officer of SCYNEXIS. “The positive effect of oral SCY-078 seen in this study was achieved at greatly reduced doses and with improved tolerability compared to our previous VVC Phase 2a study. The activity of SCY-078 in the DOVE study was consistent with that observed previously and with the fluconazole reference arm, providing reassurance of the validity of the findings across studies and confirming the clinically relevant antifungal activity of oral SCY-078 in this indication.”
All five doses of oral SCY-078 demonstrated meaningful clinical and mycological activity, confirming the potent antifungal effect of SCY-078 observed in our previous VVC Phase 2a study. The lowest SCY-078 dose regimen of 600mg exhibited the optimal combination of overall clinical and mycological activity and favorable tolerability. Pending the End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA), SCYNEXIS believes that the 600mg dose of SCY-078 (given as two doses of 300mg every 12 hours) is the optimal dose regimen for use in the VVC Phase 3 registration program.
The SCY-078 oral dose regimen of 600mg compared favorably to the fluconazole reference arm - at the Day 10 TOC visit, clinical cure (defined as complete resolution of all signs and symptoms) was observed in 14 of 27 (52%) patients in the SCY-078 600mg dose arm and 14 of 24 (58%) patients in the FLU arm. At the Day 25 FU visit, the rate of clinical cure in the SCY-078 600mg dose arm reached 70% compared to 50% in the FLU arm.
At the Day 10 TOC visit, in the mITT population, the mycological eradication rate in the SCY-078 600mg dose arm (63%) was comparable to the FLU arm (63%). Similar to clinical cure, mycological eradication at the Day 25 FU visit was numerically higher in the SCY-078 600mg dose arm (48%) compared to the FLU arm (38%).
The oral SCY-078 600mg dose was generally well-tolerated, with self-limiting (generally one-day duration), mild-to-moderate gastrointestinal adverse events (AEs) being the most commonly reported. Results from the efficacy measures of the SCY-078 600mg dose observed in the DOVE study were in-line with the results observed from the prior Phase 2a Proof-of-Concept VVC study (reported in June 2016), which used doses more than four times higher, further supporting the selection of the SCY-078 600mg dose for development.
“With limited oral treatment options available for patients with VVC, and no approved products in recurrent VVC, the results observed in this Phase 2b study reinforce SCY-078’s potential to address the unmet needs in these patients,” said Marco Taglietti, M.D., President and Chief Executive Officer of SCYNEXIS. “We look forward to having our End-of-Phase 2 meeting with the FDA and starting our Phase 3 registration program for VVC, in which we anticipate oral SCY-078 will be evaluated for superiority versus placebo. These results are an important step toward realizing our goal of maximizing the broad potential of SCY-078 to treat a multitude of invasive, difficult-to-treat and often life-threatening fungal infections. I want to take the opportunity to thank all the patients and investigators who participated in this Phase 2 trial.”
In May 2018, SCYNEXIS announced the receipt of Qualified Infectious Disease Product (QIDP) and Fast Track designations from the FDA for the treatment and prevention of recurrent VVC. In June 2018, SCYNEXIS also announced at the Teratology Society 58th Annual Meeting that pre-clinical studies provide evidence that SCY-078 does not exhibit developmental or reproductive toxicity when administered to animals before and/or during gestation. The absence of teratogenicity is a critical differentiator for SCY-078, as the majority of currently available antifungal therapies, including azoles, are associated with fertility and early embryonic development toxicities.
Angulo continued, “The results from the DOVE study come on the heels of recently shared pre-clinical data suggesting that SCY-078 has no adverse impact on fertility, embryonic development or fetal development, a key differentiator versus the current standard of care for VVC. These results, combined with SCY-078’s fungicidal activity against Candida species, high penetration into vaginal tissue and enhanced antifungal activity in the acidic conditions of the vaginal environment, further support our belief that oral SCY-078 may provide a benefit to many patients with VVC.”