Novel antifungal effective against vulvovaginal candidiasis in phase 3 trials

Ibrexafungerp was superior to placebo in patients with vulvovaginal candidiasis, with statistically significant rates of clinical cure, clinical improvement and mycological eradication, according to results of the phase 3 VANISH-306 trial.

In addition, a sub-analysis of another phase 3 trial, VANISH-303, showed that ibrexafungerp (Scynexis) had clinical activity against non-albicans Candida (NAC) species, which are “difficult to treat because of their intrinsic and acquired resistance” to current treatment, according to researchers.

The findings of both analyses were presented at the American College of Obstetricians and Gynecologists Annual Clinical and Scientific Meeting, which was held virtually. They support “ibrexafungerp’s potential to treat a broad range of Candida species,” including fluconazole-resistant strains, as well as patients with severe vulvovaginal candidiasis (VVC), Nkechi Azie, MD, vice president of clinical development and medical affairs at Scynexis, said in a press release.

“Candida albicans has been the prominent species causing vaginal yeast infections; however, we are seeing a notable shift in the etiology candidiasis, with non-albicans Candida species gaining prominence,” she said in the release. “Fluconazole is not recommended for treatment of non-albicans Candida VVC, often because of a high rate of resistance, leaving no oral treatment options for this difficult-to-treat patient population.”

For VANISH-306, Azie and colleagues randomly assigned 188 patients (median age, 32 years; white, 81.4%) from the U.S. and Bulgaria to receive 300 mg ibrexafungerp and 84 patients (median age, 32 years; white, 82.1%) to placebo. For VANISH-303, the researchers randomly assigned 188 patients (median age, 32.5 years; white, 54.8%) from the U.S. to receive 300 mg ibrexafungerp and 98 patients to placebo. The sub-analysis of VANISH-303 included 19 patients with NAC pathogens in the ibrexafungerp group and 13 patients with NAC pathogens in the placebo group.

The primary endpoint of both VANISH-306 and VANISH-303 was clinical cure, which the researchers defined as complete resolution of signs and symptoms at a test-of-cure visit on day 10. The follow-up period was 25 days.

In the VANISH-306 trial, 63.3% of patients who received ibrexafungerp had clinical cure at the test-of-cure visit vs. 44% of patients who received placebo (RR = 1.38; 95% CI, 1.07-1.78). In addition, 72.3% of patients in the ibrexafungerp group had clinical improvement vs. 54.8% in the placebo group (RR = 1.28; 95% CI, 1.04-1.57), and 58.5% had mycological eradication vs. 29.8% in the placebo group (RR = 1.85; 95% CI, 1.33-2.58). At day 25, 73.9% of patients treated with ibrexafungerp had symptom resolution.

In the VANISH-303 trial, 50.5% of patients who received ibrexafungerp had clinical cure at the test-of-cure visit; 49.5% had mycological eradication and 64.4% had clinical improvement. The rate of clinical cure in the NAC subgroup was 42.1%, but the researchers reported that “there were too few subjects with NAC in the study to draw a strong conclusion.” At day 25, the proportion of patients with symptom resolution was 59.6% overall and 52.6% among those with NAC.

The most common adverse events in both studies were gastrointestinal symptoms. Among VANISH-303 participants in the treatment group, 25.5% reported diarrhea, 16.2% reported nausea, 6.9% reported abdominal pain and 2% reported vomiting; the researchers wrote that most cases were “mild to moderate, lasting one day.” Among VANISH-306 participants in the treatment group, 9.4% reported diarrhea, 8.4% reported nausea and 2.7% reported abdominal pain; like the VANISH-303 trial, most cases were mild or moderate.

Scynexis announced in October that it submitted a new drug application to the FDA for ibrexafungerp for the treatment of vulvovaginal candidiasis. The target action date is set for June 1, 2021. According to the company’s website, another phase 3 trial investigating the efficacy of ibrexafungerp in preventing recurrent vulvovaginal candidiasis is ongoing.

References:

• Azie N, et al. Phase 3 oral ibrexafungerp study in vulvovaginal candidiasis (VANISH-303): Outcomes in non-. Presented at: American College of Obstetricians and Gynecologists Annual Clinical and Scientific Meeting; April 30-May 4, 2021 (virtual meeting).
• SCYNEXSIS. Pipeline. Accessed May 4, 2021. Available at: https://www.scynexis.com/pipeline.
• SCYNEXIS. SCYNEXIS presents data at 2021 ACOG demonstrating the positive outcome and sustained response of investigational oral ibrexafungerp (Brexafemme) in difficult-to-treat patients with vaginal yeast infections. Accessed May 4, 2021. Available at: https://www.scynexis.com/news-media/press-releases/detail/236/scynexis-presents-data-at-2021-acog-demonstrating-the.
• Sobel R, et al. Efficacy and safety of oral ibrexafungerp in the treatment of vulvovaginal candidiasis: A phase 3 study (VANISH-306). Presented at: American College of Obstetricians and Gynecologists Annual Clinical and Scientific Meeting; April 30-May 4, 2021 (virtual meeting).