Oral Ibrexafungerp for Vulvovaginal Candidiasis Treatment: An Analysis of VANISH 303 and VANISH 306

Abstract

Background: Ibrexafungerp is a novel antifungal treatment for acute vulvovaginal candidiasis (VVC). Using pooled data from two phase three studies (VANISH 303 and 306) in the treatment of acute VVC, this analysis sought to determine the effectiveness of ibrexafungerp in various patient subgroups that may impact outcomes. Materials and Methods: Data from VANISH 303 (NCT03734991) and VANISH 306 (NCT03987620) evaluating ibrexafungerp 300 mg twice daily (BID) for 1 day versus placebo, were pooled and analyzed to determine clinical cure rate, clinical improvement, and mycological cure at the test-of-cure visit (day 11 ± 3) and symptom resolution at the follow-up visit (day 25 ± 4) in the overall population. Patient subgroups analyzed included race, body mass index (BMI), baseline vulvovaginal signs and symptoms (VSS) score, and Candida species. Results: At the test-of-cure visit, patients receiving ibrexafungerp, compared with those who received placebo, had significantly higher rates of clinical cure (56.9% [214/376 patients] vs. 35.7% [65/182 patients]), clinical improvement (68.4% [257/376 patients] vs. 45.1% [82/182 patients]), and mycological cure (54.0% [203/376 patients] vs. 24.2% [44/182 patients]; all p < 0.0001). At the follow-up visit, patients receiving ibrexafungerp had sustained responses with higher symptom resolution rates (66.8% [251/376 patients]) versus placebo (48.4% [88/182 patients]; p < 0.0001). Race, BMI, baseline VSS score (including VSS severity score 13-18), and Candida species infection did not adversely affect clinical cure rates. Safety analysis results were consistent with the individual studies. Conclusions: Ibrexafungerp provides a safe and well-tolerated first-in-class fungicidal, 1-day oral treatment for patients with acute VVC, the first new therapy in >20 years. Clinical Trial Registration Number: NCT03734991.

Keywords: Candida albicans; antifungal; ibrexafungerp; placebo; vulvovaginal candidiasis.

Conflict of interest statement

O.G. has served on the advisory board for SCYNEXIS, Inc., and Evvy. She is a contributor to Up-To-Date and Merck Manuals.

R.S. is a consultant for SCYNEXIS, Inc., and Mycovia Pharmaceuticals.

P.N. has served as a principal investigator and as a consultant for SCYNEXIS, Inc., Mycovia Pharmaceuticals, and Hologic, Inc.

S.R.G. has served on an advisory board for SCYNEXIS, Inc.

M.S. has served on an advisory board for SCYNEXIS, Inc., and received honorarium for Audio Roundtable discussion.

B.F. has received payment or honoraria for serving as a consultant and/or speaker for Palatin Technologies, Mayne Pharma, Agile Therapeutics, Inc., SCYNEXIS, Inc., Bonafide, Inc., and Solv WellnessTM. B.F. has also served on advisory boards for Solv Wellness and SCYNEXIS, Inc., and served as secretary for the International Society for the Study of Women's Sexual Health (ISSWSH).

S.L. has no conflicts to report.

T.K., N.E.A., and D.A. are employed by and hold stocks in SCYNEXIS, Inc.

J.D.S. has received research funds from SCYNEXIS, Inc., and Mycovia Pharmaceuticals.

Figures

FIG. 1.

Patient disposition of the pooled analysis of the VANISH 303 and VANISH 306 studies. aFive patients experienced a TEAE not related to ibrexafungerp that led to study discontinuation (bacterial vaginosis, n = 4; diabetes mellitus, n = 1). mITT, modified intention to treat; TEAE, treatment-emergent adverse event.

FIG. 2.

Efficacy outcomes for the VANISH 303, VANISH 306, and pooled analysis studies. BID, twice daily; mITT, modified intention to treat.

FIG. 3.

Clinical cure rates at the test-of-cure visit in patient subgroups in pooled analyses of VANISH 303 and VANISH 306 patients (mITT population). aInsufficient number of patients to analyze ≥65 years of age, Asian, and Race (other) subgroups. BMI, body mass index; mITT, modified intention to treat; TOC, test-of-cure; VSS, vulvovaginal signs and symptoms.