Image credit: Mycovia Pharmaceuticals
This week, Mycovia Pharmaceuticals announced it has enrolled its first participant for its phase 2 PLATFORM-CM clinical trial evaluating oteseconazole for cryptococcal meningitis.1
This is an open-label randomized trial with single or potentially multiple interventional arms to compare the efficacy and safety of antifungal investigational therapies, including oteseconazole, to the standard of care WHO first-line therapy in treating cryptococcal meningitis. The clinical trial will be conducted at 3 sites in Uganda and will involve up to 200 participants who will be treated for 18 weeks with oteseconazole. 1
The study’s designers and principal investigators are David Boulware, MD, professor of Medicine, Infectious Disease and International Medicine at the University of Minnesota, School of Public Health, and David Meya, PhD, associate professor at the School of Medicine at the College of Health Sciences, Makerere University in Uganda. 1
“We are excited to initiate this important study and enroll our first research participant,” Boulware said in a statement. “Our goal is to generate meaningful data that will show a reduction in death for patients that cannot use or who have developed resistance to current standard of care treatments.” 1
Cryptococcal meningitis causes an estimated 152,000 cases and 112,000 deaths annually, and is one of the leading causes of death among people living with HIV in Africa. Several challenges exist with the current standard of care therapy including medication access and stability, supplier limitations, and substantial toxicity. Additional treatments are needed for cryptococcal meningitis, particularly those which have less toxicity, greater efficacy, a prolonged half-life, and minimal drug-drug interactions. The World Health Organization has identified Cryptococcus as a critical fungal priority pathogen. 1
About the Therapy
Oteseconazole is designed to selectively inhibit fungal CYP51, which is required for fungal cell wall integrity, and this interaction is also toxic to fungi, resulting in the inhibition of fungal growth. Preclinical studies have demonstrated that oteseconazole is potent against fluconazole-sensitive and -resistant strains of Cryptococcus. 1
“This study will serve to further evaluate oteseconazole beyond its currently approved indication and expand upon the encouraging preclinical data that suggests oteseconazole may have clinical utility in treating this serious fungal infection of the brain and central nervous system,” Mycovia Chief Development Officer Stephen Brand, PhD, said in a statement.
Previous FDA Approval
In April 2022, the FDA approved oteseconazole (marketed under the name Vivjoa), the first and only medication authorized for chronic yeast infection. Vivjoa, oteseconazole capsules, reduces the incidence of recurrent vulvovaginal candidiasis (RVVC) in women with a history of RVVC who are not planning to get pregnant. Oteseconazole was previously granted Fast-Track and Qualified Infectious Disease Product designations by the FDA.2
The approval was base on positive results from 3 different phase 3 clinical trials of oteseconazole. The 2 global VIOLET studies and 1 US-focused ultraviolet study included 875 patients at 232 sites in 11 countries.2
In the global studies, 93.3% and 96.1% of women with RVVC who received oteseconazole did not have a recurrence in the 48-week maintenance period. This is compared to the placebo recipients, among whom 57.2% and 60.6% did not experience recurrence.2
In the ultraviolet study, 89.7% of women with RVVC who received oteseconazole cleared their initial yest infection and had no recurrent infections for the 50-week maintenance period. 57.1% of women who received fluconazole and placebo had no recurrence. The most frequently reported adverse events were headache and nausea, occurring in 7.4% and 3.6% of trial participants, respectively.2
