Vulvovaginal Candidiasis

Ibrexafungerp for Vulvovaginal Candidiasis

Ibrexafungerp for Vulvovaginal Candidiasis

Ibrexafungerp (formerly SCY-078), if approved, may represent an optimal therapy for the treatment of acute vulvovaginal candidiasis (VVC) and for prevention of recurrence. Ibrexafungerp is orally administered and is extensively distributed into vaginal tissues. It is also fungicidal, with a broad spectrum of activity and enhanced activity in the acidic pH at the site of infection.

Acute VVC and recurrent VVC are serious conditions with significant morbidity and with very limited oral treatment options. No product is approved for the prevention of recurrent VVC, and current treatment alternatives have significant limitations, particularly in patients with other comorbidities and those who are taking certain concomitant medications, are pregnant or are experiencing episodes caused by an azole-resistant micro-organism.

What is Vulvovaginal Candidiasis?

VVC, commonly known as a "vaginal yeast infection," is the second most common cause of vaginitis and is usually caused by Candida spp. It affects approximately 70-75% of women at least once in their lifetime, with 40-50% of these women experiencing more than one episode. The majority of VVC episodes are uncomplicated cases with sporadic mild-to-moderate infections. The remaining complicated cases are severe and/or recurring infections.

Market Need

VVC can be associated with substantial morbidity, including significant genital discomfort, reduced sexual pleasure, psychological distress and loss of productivity. Diagnosis and treatment, combined with lost productivity, are estimated to cost $1.0 billion per year in the U.S. Current treatments for VVC include over-the-counter (OTC) topical azole antifungals and the prescription oral azole antifungal, fluconazole.

  • Fluconazole is the only orally-administered antifungal currently approved for VVC in the U.S., with a reported therapeutic cure rate of 55%.
  • Management of VVC during pregnancy and treatment of moderate-to-severe VVC, recurrent VVC and VVC caused by fluconazole-resistant Candida are not fully addressed by oral fluconazole.
  • There are no oral alternatives for VVC patients who do not respond to or tolerate fluconazole, and there are no FDA-approved products for the treatment of recurrent VVC.

We believe that ibrexafungerp, if approved for the treatment of VVC, may provide a significant benefit for patients not satisfied with existing therapies

~70-75% of women of reproductive age will have at least one episode of VVC during their lifetime
~40-45% of women will experience two or more episodes of VVC
~650K patients suffer from recurrent complicated VVC (at least four episodes during a 12-month period)

*Data on File (2015 IMS Consulting Group study, commissioned by SCYNEXIS).

Ibrexafungerp (formerly SCY-078) could provide a first-line therapy for recurrent VVC, for which there is currently no FDA-approved treatment, and be the only oral, non-azole, fungicidal treatment for moderate and severe cases of VVC.

  • Ibrexafungerp's broad spectrum activity (including against fluconazole-resistant strains), enhanced activity at acidic pH and high penetration in the vaginal tissue may allow ibrexafungerp to address the current unmet needs in this indication and improve the quality-of-life of these patients.
  • Ibrexafungerp is fungicidal against most Candida isolates, in contrast with fluconazole, which is fungistatic. Ibrexafungerp's "cidal" activity (i.e., killing the pathogen) may provide an advantage in preventing recurrences.

“Many of the unresolved clinical issues in managing women with recurrent VVC would disappear if truly fungicidal drugs and regimens were available.”

- Dr. Jack D. Sobel
Current Infectious Disease Reports 2006,8:481–486

Clinical Trial Results

Clinical experience to date has shown promising evidence of the antifungal activity of  Ibrexafungerp (formerly SCY-078) in patients with Candida infections.

(ClinicalTrials.gov Identifier: NCT02679456)

PK/Efficacy
  • Demonstrated activity vs. Candida
    • Numerically higher clinical cure rates than fluconazole
    • High long-term efficacy
    • Low relapse rate at four months
Safety/Tolerability
  • Safe and well-tolerated
    • No serious AEs or discontinuations
    • Gastrointestinal (GI) events were mild to moderate and of short-duration

Enrollment Completed for Phase 2b Dose-Finding Study in Acute VVC (the DOVE Study)

The DOVE study is a randomized, multicenter, double-blind, active-controlled, dose-finding study designed to identify a safe and efficacious dose regimen of oral ibrexafungerp (formerly SCY-078) in adult female patients. Approximately 180 patients with moderate to severe acute VVC were randomized to one of five different regimens of oral ibrexafungerp or oral fluconazole, the current standard of care (SoC). Efficacy will be measured by the percentage of patients with clinical cure (complete resolution of signs and symptoms) at the test-of-cure visit at day 10 (primary endpoint) and at a follow-up visit on day 25. Mycological eradication (negative fungal culture) will also be evaluated at the same time points. Enrollment in the trial was recently completed, and SCYNEXIS expects top-line results by July 2018.

Learn more here

Clinical Development Plan

SCYNEXIS anticipates that the dose regimen selected from the DOVE study will be subsequently evaluated in Phase 3 studies following an End-of-Phase 2 meeting with the FDA. SCYNEXIS expects to initiate the Phase 3 clinical program in the fourth quarter of 2018 and file a New Drug Application (NDA) for acute VVC in 2020.

Sources

Preliminary assessment (to be further validated). SCYNEXIS Primary HCPs and Payers Market Research.

CDC: Vaginal Candidiasis.