Michael L. Krychman, MD, and Jack D. Sobel, MD, review the clinical implications of the recent approval of oteseconazole, which has been shown to be efficacious and well tolerated in RVVC treatment.
Michael L. Krychman, MD: Let’s turn to the recently approved drug oteseconazole. Can you give me a high-level overview of this novel drug, which was just approved for recurrent VVC [vulvovaginal candidiasis]? It’s the only drug approved for recurrent VVC. Feel free to highlight some of the high-level data from the VIOLET and ultraVIOLET studies. Are there any potential problems or pitfalls? This is exciting. There haven’t been a lot of new developments in the field of VVC or RVVC [recurrent VVC]. It’s first in class for recurrent VVC. I’d love to hear your general take, and then we’ll dive deep into things that are emerging.
Jack D. Sobel, MD: Oteseconazole was approved in August 2022 for the treatment of recurrent candidal vaginitis. It’s the first drug approved. Even though fluconazole was used for 20 years, nobody ever applied for approval. No company was interested in getting the drug approved. Along comes oteseconazole, which is a second cousin of fluconazole, tetrazole, and clotrimazole, but it’s still the same family that’s been designed to be more potent than fluconazole in the test tube against yeast and not only the common Candida albicans but also the non–Candida albicans species, like Candida glabrata and Candida krusei. It’s also designed to have an affinity for the yeast target enzymes, which are present in human epithelial cells and subvert. The affinity for the fungus target toward enzymes is far greater than it is for fluconazole. It’s more active and more potent, but it doesn’t have the toxicity that’s part of fluconazole’s identity. It’s a safer drug.
Remember, fluconazole isn’t approved; it’s contraindicated in pregnancy. The biggest drawback of fluconazole is that it can’t be used for pregnancy, yet many practitioners continue to do this unwisely. I never prescribe fluconazole in pregnancy. Along comes oteseconazole, which is more potent. Most important, in addition to its potency, it doesn’t affect QTc [QT interval corrected for heart rate] and doesn’t have the same tendency to cause lots of drug injury reactions. It’s a well-tolerated, safe drug for patients with candidal vaginitis. It has increased potency, and it has 1 other major advantage: it stays in the tissues; it sticks around. That’s in contrast with fluconazole, which has a half-life of under 30 hours, closer to 20 hours. Oteseconazole has a half-life of about 130 days.
The reason why this drug was designed to be effective in recurrent candidal vaginitis is that if it stays in the tissues for a prolonged period of time, it’s going to prevent vaginal recolonization. Long after they’ve stopped taking the medication, patients remain free of recolonization. Not forever—you can’t change your genes—but that’s part of its potency. In clinical studies done with women all over the world, called VIOLET and ultraVIOLET, the drug was found to be highly effective in reducing attacks of recurrent candidal vaginitis. It reduces not only C albicans, which is 85% to 90% of recurrent infections, but in the other 10%, which is when you start getting resistance because it’s more potent.
Michael L. Krychman, MD: The issue we’re hearing is from the clinical perspective. I appreciate your discussion about the tissue, the half-life, and staying effective. That can be looked at as a double-edged sword, in terms of a half-life of 2 years and drug exposure. With every drug, there are positives and negatives. No one is doubting efficacy or safety. But there are some discussions about potential shortcomings, study population vs approved population, long half-life, and drug exposure can be problematic. I appreciate your insight about the benefits of a long half-life. That’s very important in terms of maintaining the effectiveness, and it’s the only drug approved for recurrent VVC.
Transcript Edited for Clarity