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.
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.
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.
*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.
- Dr. Jack D. Sobel
Current Infectious Disease Reports 2006,8:481–486
Clinical experience to date has shown promising evidence of the antifungal activity of Ibrexafungerp (formerly SCY-078) in patients with Candida infections.
Identified 600 mg dose as having optimal combination of activity and tolerability - plan to move this into Phase 3.
(ClinicalTrials.gov Identifier: NCT03253094)
| Treatment Groups Total Dose in mg |
Reginmen | ITT / mITT (# of patients) |
|---|---|---|
| 600mg SCY-078 | 300mg BID for 1 day | 30 / 27 |
| 750mg SCY-078 | 750mg QD for 1 day | 32 / 26 |
| 900mg SCY-078 | 450mg BID for 1 day | 28 / 21 |
| 900mg SCY-078 | 150mg BID for 3 days | 32 / 29 |
| 1080mg SCY-078 | 300mg BID for 3 days | 32 / 26 |
| 150mg Fluconazole | 150mg QD for 1 day | 32 / 24 |
Results based on mITT population | * No rescue antifungal use.
Signs and Symptoms [S&S] score defined as a composite endpoint of the subject’s reported symptoms (burning, itching and irritation) and the investigator’s assessed signs (swelling, redness and excoriations). Each sign and symptom can be absent, mild, moderate or severe, with a corresponding score from 0 to 3. The total composite scale goes from 0 to 18 points.
Results based on mITT population.
Mean signs and symptoms score based on 0-18 scale.
P value based on change from baseline score mean difference between SCY-078 600mg and FLU.
SCY-078 Phase 2 Study in Moderate and Severe Vulvovaginal Candidiasis (VVC)
Randomized, multicenter, active controlled, evaluator-blinded study of oral SCY-078 compared to oral fluconazole in adult female patients with acute vulvovaginal candidiasis (VVC). A total of 96 patients with an acute moderate to severe, symptomatic episode of VVC were randomized in a 1:1:1 ratio to receive either three daily doses or five daily doses of SCY-078 or oral fluconazole, at the labeled dose regimen of 150mg single dose. Efficacy was evaluated based on the proportion of patients achieving clinical cure (resolution of all signs and symptoms, score=0 and 1) mycological eradication and therapeutic cure (combination of both clinical cure and mycological eradication) at day 24 (+/-3) after initiation treatment, in line with draft guidelines from the FDA.
(ClinicalTrials.gov Identifier: NCT02679456)
The Phase 2a POC VVC Study and the Phase 2b DOVE study showed comparable efficacy results, providing reassurance of reliability of findings across studies.
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.
Indication
2018
2019
2020
2021
Acute Vulvovaginal Candidasis
Phase 2b DOVE Results
Two Phase 3 Acute VVC Studies
Potential NDA filing in H2:2020
Recurrent Vulvovaginal Candidasis
One Phase 3 Recurrent VVC Study
Potential sNDA filing in 2021
Preliminary assessment (to be further validated). SCYNEXIS Primary HCPs and Payers Market Research.
CDC: Vaginal Candidiasis.
