Ibrexafungerp for vaginal yeast infection: a phase III trial in China

In this Chinese phase III trial, one day of oral ibrexafungerp led to more day-11 clinical cures than placebo among adults with symptomatic, microscopy-positive vaginal yeast infection. The study did not compare ibrexafungerp with fluconazole or topical azoles, so it does not establish a preferred route or a new treatment action.

This is a large randomized placebo-controlled study of an oral non-azole treatment in a Chinese population. It adds a useful treatment result to the research record while leaving oral-versus-topical azole comparisons unanswered.

The phase III trial took place at 31 tertiary hospitals in China. It randomized 369 participants (246 to ibrexafungerp and 123 to placebo). The safety set included 244 and 123 participants; the modified intention-to-treat set included 239 and 121 who had a positive baseline Candida culture and received at least one dose. Participants were aged 18–64 and had symptoms, microscopy findings consistent with Candida, and vaginal pH ≤4.5. Pregnancy, other vaginal infections, immunosuppression, and uncontrolled diabetes (HbA1c >9%) were exclusions.

Participants received oral ibrexafungerp 300 mg twice daily for one day or matching placebo. The primary outcome was clinical cure, defined as a vulvovaginal signs and symptoms (VSS) score of 0, at test-of-cure on day 11 ± 3. Secondary outcomes included negative Candida culture, overall response (both clinical cure and mycological eradication), clinical improvement (VSS score ≤1), and symptom resolution at follow-up on day 25 ± 4. Rescue antifungal treatment at or before test-of-cure and missing categorical responses counted as failures; missed follow-up visits also counted as failures.

At test-of-cure, clinical cure was 122/239 (51.0%) with ibrexafungerp and 31/121 (25.6%) with placebo: a difference of 25.3 percentage points (95% CI 15.31–35.21; p<0.001). Mycological eradication was 133/239 (55.6%) versus 22/121 (18.2%). Table 2 reports a difference of 37.5 points (95% CI 28.18–46.88; p<0.001), but the Results prose reports 38.8 points (95% CI 29.46–48.21). The article does not explain the discrepancy, so the table estimate is used here with the conflict stated.

Overall response was 81/239 (33.9%) versus 10/121 (8.3%), a difference of 25.6 points (95% CI 17.84–33.38; p<0.001). Clinical improvement was 196/239 (82.0%) versus 59/121 (48.8%), a difference of 33.2 points (95% CI 23.03–43.30; p<0.001). At follow-up, complete symptom resolution was 178/239 (74.5%) versus 48/121 (39.7%), a difference of 34.8 points (95% CI 24.45–45.11; p<0.001).

In the safety set, at least one treatment-emergent adverse event occurred in 154/244 (63.1%) ibrexafungerp participants and 52/123 (42.3%) placebo participants. Gastrointestinal events were reported in 124/244 (50.8%) and 13/123 (10.6%); diarrhea in 105/244 (43.0%) and 6/123 (4.9%); nausea in 22/244 (9.0%) and none; and abdominal pain in 10/244 (4.1%) and 2/123 (1.6%). Nearly all events were mild or moderate, no event led to study discontinuation, and the two serious adverse events occurred in the placebo group and were reported as unrelated to treatment. One pregnancy was reported in the ibrexafungerp group and ended in elective abortion; this does not establish pregnancy safety.

These estimates apply to the tested one-day regimen against placebo in adults aged 18–64 with symptomatic, microscopy-positive acute VVC at Chinese tertiary hospitals. Pregnancy, other vaginal infections, immunosuppression, and uncontrolled diabetes were excluded. The trial does not compare ibrexafungerp with oral or topical azoles, assess recurrent-infection maintenance, or determine what is available or suitable in either locale.

There was no active comparator, and follow-up ended at day 25. The study was conducted in China and excluded pregnancy and several complex conditions; only 10 participants in the modified intention-to-treat set had diabetes, so subgroup estimates cannot guide care for people with diabetes. The authors examined species and fluconazole-susceptibility subgroups, including post-hoc analyses; these are exploratory and do not justify resistance or treatment-failure advice. The Results prose and Table 2 give conflicting mycological rate differences. The study was manufacturer-funded, with the sponsor involved from design through publication authorization and three authors employed by the sponsor. The linked online supplement was not independently reviewed; no results available only there are summarized.

Contextual. This placebo-controlled trial adds a result for one oral non-azole regimen in Chinese adults with acute VVC. It does not resolve comparisons of oral and topical azoles, recurrent-treatment evidence, or locale-specific treatment choices.

No practical change. The trial does not establish an azole route preference or replace current, exact-product guidance on treatment access, pregnancy, contraindications, and interactions.

Jiangsu Hansoh Pharmaceutical Group Co., Ltd. funded and sponsored the study and participated in study design, monitoring, data collection, analysis and interpretation, reporting, and authorization of results for publication. Qiong Wu, Wen Jia, and Chuan Li were company employees; the other authors reported no conflicts.

Read the original publication (published online April 3, 2024). The linked supplementary material was not independently reviewed for this summary.