Oteseconazole (VIVJOA; Mycovia Pharmaceuticals) capsules have displayed positive safety and efficacy data compared to fluconazole for treating vulvovaginal candidiasis (VVC), according to results of a phase 3 trial published in Antimicrobial Agents and Chemotherapy.
Takeaways
- Oteseconazole capsules, compared to fluconazole, have demonstrated positive safety and efficacy in the treatment of severe vulvovaginal candidiasis (VVC), according to results from a phase 3 trial.
- Vulvovaginal candidiasis is a common condition, affecting approximately 80% of women at least once. Symptoms include vulvovaginal itching, irritation, soreness, burning, redness, fissuring, vaginal discharge, and dyspareunia.
- Oteseconazole, a novel fungal CYP51 inhibitor, exhibits over 2,000-fold selectivity for fungal CYP51 compared to human CYPs, indicating increased safety. This selectivity addresses concerns over decreased activity against non-Candida albicans species.
- The phase 3 trial involved women aged 18 to 75 with severe VVC symptoms. Participants were randomized to receive either oteseconazole or fluconazole, and the study assessed therapeutic and mycological cure rates, along with safety measures.
- Oteseconazole showed superior efficacy compared to fluconazole, with higher rates of therapeutic cure (66.88% vs. 45.91%), mycological cure (82.50% vs. 59.12%), and clinical cure (71.25% vs. 55.97%) at day 28. Treatment-emergent adverse events were reported in both groups, with a slightly higher percentage in the oteseconazole group (51.3% vs. 42.9%), all of which were mild or moderate in severity.
VVC, presenting as vulvovaginal itching, irritation, soreness, burning, redness, fissuring, vaginal discharge, and dyspareunia, occurs at least once in approximately 80% of women. While oral fluconazole has displayed efficacy in managing VVC, there are concerns over decreased activity against non-Candida albicans (C. albicans) species.
Oteseconazole, a novel fungal CYP51 inhibitor, has displayed an over 2,000-fold selectivity for fungal CYP51 compared to human CYPs, indicating increased safety. Investigators conducted a study to evaluate the efficacy and safety of oteseconazole compared to fluconazole for treating severe VVC.
Participants included women aged between 18 and 75 years with vulvovaginal signs and symptoms (VSS) scores of 7 or greater and positive Candida species presentation. Reproductive-capable women needed a negative pregnancy test and contraception use throughout the study and for 6 months following the final treatment administration.
Exclusion criteria included recurrent VVC (RVVC) or RVVC history with concomitant vulvovaginitis, using antifungal treatments, estrogen replacement therapy within 7 days prior to randomization, systemic corticosteroid treatment use within 30 days before randomization, cervical cancer history, and moderate to severe hepatic or renal disorders.
Participants were randomized 1:1 to receive either oteseconazole or fluconazole. The otesconazole group received oteseconazole 600 mg and fluconazole matching placebo 150 mg on day 1, oteseconazole 450 mg on day 2, and fluconazole matching placebo 150 mg on day 4.
The fluconazole group received fluconazole 150 mg and oteseconazole matching placebo 600 mg on day 1, oteseconazole matching placebo 450 mg on day 2, and fluconazole 150 mg on day 4. Clotrimazole vaginal tablets were provided in patients with worsened symptoms based on investigator decisions.
VVC VSS scores at baseline, day 14, and day 28 were used to determine efficacy. Therapeutic cure was the primary endpoint, defined by clinical and mycological cure. Adverse events, physical examinations, vital signs, and electrocardiograms were used to determine safety.
There were 322 women included in the final analysis, 319 of whom had a positive Candida species screening and were included in efficacy assessments. Of the participants, 316 completed the study.
Baseline VSS scores of 8.7 in the oteseconazole group and 8.4 in the fluconazole group were reported. A positive C. albicans screening was reported in 78.1% of patients and C. glabrata by 15.4%.
Therapeutic cure at day 28 was reported in 66.88% of the oteseconazole group and 45.91% of the fluconazole group. Among patients with a positive culture of C. albicans, these rates were 76.56% and 56.20%, respectively.
Mycological cure was also significantly higher in the otesconazole group, at 82.50% vs 59.12% in the fluconazole group. Clinical cure rates in these groups were 71.25% vs 55.97%, respectively.
Similar results were observed at day 14, at 52.50% vs 38.36%, respectively, for therapeutic cure and 81.88% vs 66.67%, respectively, for mycological cure. These results were consistent in subgroups with a positive culture of C. albicans. However, clinical cure rates at day 14 were similar between the groups, at 56.88% vs 50.31%, respectively.
One or more treatment-emergent adverse event (TRAE) was reported in 51.3% of the otesconazole group and 42.9% of the fluconazole group, all of which were mild or moderate in severity. Common TAEs in the oteseconazole group were urinary tract infection, bacterial vulvovaginitis, dizziness, and headache.
These results indicated safety and efficacy of oteseconazole over fluconazole for treating severe VVC. Investigators concluded oteseconazole can be used as treatment in women with severe VVC.
Reference
Wang X, Chen L, Xiong Z, et al. Oteseconazole versus fluconazole for the treatment of severe vulvovaginal candidiasis: a multicenter, randomized, double-blinded, phase 3 trial. Antimicrobial Agents and Chemotherapy. 2024;68(1). doi:10.1128/aac.00778-23
