21 Jan Oteseconazole: Mycovia Pharmaceuticals Reports Positive Phase 3 Data for their Oral Drug for Recurrent Vaginal Yeast Infections
MedicalResearch.com interview with:
Dr. Stephen Brand, Chief Development Officer
Dr. Stephen Brand discusses the results of Mycovia’s three Phase 3 studies for recurrent vaginal yeast infections (RVVC )and what’s next for the company.
MedicalResearch.com: What is the background for these Phase 3 studies?
Answer: Our Phase 3 clinical program for our oral therapy oteseconazole was comprised of three trials enrolling more than 870 patients at 176 sites across 11 different countries.
Two of these trials, referred to as VIOLET were identical Phase 3 randomized, double-blind, placebo-controlled clinical trials to evaluate the safety of oteseconazole and its ability to prevent episodes of recurrent vulvovaginal candidiasis (RVVC), commonly referred to as chronic yeast infection. The trials took place over 48 weeks in subjects with an established disease history of at least three episodes of acute VVC in the past 12 months. More than 650 patients randomized at 125 sites across 11 countries.
The VIOLET trials consisted of two parts: During the first part of the study which lasted two weeks after patients presented with an active VVC episode, patients were treated with three sequential 150mg doses of fluconazole. The second part consisted of 12 weeks, when the patient either took oteseconazole 150mg or a placebo once weekly (according to a random assignment), and then a 36-week follow-up period.
In addition, subjects participating in the VIOLET trials in the U.S. who remained infection-free at their Week 48 visit were offered the opportunity to participate in an extension study and are being monitored for an additional 48 weeks to further define the long-term protection profile of oteseconazole. Eighty-five subjects are enrolled.
The third Phase 3 study, called ultraVIOLET, was designed to complement and extend VIOLET as a 50-week randomized, double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of oteseconazole. In addition the study compared the effectiveness of oteseconazole compared to fluconazole, the current standard of care, to treat an acute VVC infection in the RVVC population. A total of 220 patients were randomized at 51 sites in the U.S. for the ultraVIOLET trial.
The ultraVIOLET trial consisted of two parts: In the first part of the study RVVC subjects presenting with an active infection were randomized to receive either 2 days of dosing with oteseconazole or 3 sequential 150 mg doses of fluconazole (every 72 hours). The second part consisted of 11 weeks, when the patient took either oteseconazole or a placebo weekly (according to the random assignment from the first part of the study), and then a 37-week follow-up period.
MedicalResearch.com: Why is Mycovia focusing on recurrent vaginal yeast infections?
Answer: RVVC is a debilitating infectious condition that affects nearly 138 million women worldwide each year. While primary physical symptoms include vaginal itching, burning, irritation and inflammation, RVVC also impacts quality of life to a degree comparable to asthma and worse than diseases such as migraine.
Historically, investment and innovation in women’s health have been limited. However, Mycovia is committed to recognizing and empowering those living with unmet medical needs, which is one of the reasons we focused first on developing oteseconazole for RVVC, a disease for which there are currently no approved drugs in the US. We are proud to be at the forefront of a growing movement in healthcare to focus on conditions like RVVC, which can negatively impact so much of a woman’s life physically, personally and emotionally.
MedicalResearch.com: What are the main findings of the Phase 3 studies?
Answer: We’re delighted by the positive topline results from the VIOLET and ultraVIOLET studies of oteseconazole in patients with RVVC, with the data clearly differentiating oteseconazole from other antifungal agents.
Topline data shows that the two VIOLET studies successfully met their primary endpoint (p-value <0.001), defined as the proportion of subjects with one or more culture-verified acute VVC episodes during the maintenance phase (post-randomization through Week 48) in the intent-to-treat population. All key secondary endpoints met statistical significance (p-value <0.001) through Week 48.
Oteseconazole also protected more than 90% of participants from having a recurrence during the maintenance phase. Oteseconazole was able to prevent a recurring infection over the course of these 48-week studies in 96% and 93% of women.
The results from ultraVIOLET demonstrate oteseconazole’s effectiveness in treating acute episodes of VVC and reinforce its efficacy and safety profile in treating RVVC compared to fluconazole. The ultraVIOLET study met all primary and secondary endpoints. Over 50 weeks, patients treated with oteseconazole had a recurrence rate of 5.1%, compared to 42.2% in patients treated with fluconazole followed by placebo (p-value < 0.001). This means oteseconazole prevented a recurring episode in 95% of women for approximately one year. Oteseconazole was shown to be non-inferior to fluconazole in the resolution of signs and symptoms at Day 14.
MedicalResearch.com: How does oteseconazole differ from the current standard of care for RVVC?
Answer: Despite RVVC’s impact and high prevalence, there are currently no FDA-approved treatments in the U.S. The current standard of care is a first-generation antifungal for yeast infections called fluconazole. Although fluconazole is not approved to treat recurrent VVC infections, it is often used, despite the fact most of these women will experience a recurrence once treatment is stopped. There are also numerous safety concerns such as liver toxicity, increased risk of miscarriage and drug-to-drug interactions that limit chronic dosing of fluconazole.
Oteseconazole was designed with the goal of having greater selectivity, fewer side effects and improved efficacy as compared to fluconazole. Oteseconazole more potently inhibits fungal CYP51 than current azoles and avoids off-target interactions, resulting in greater CYP selectivity, less toxicity and greater efficacy.
To date, oteseconazole is the only product to be studied in three Phase 3 trials in women suffering from RVVC. The VIOLET and ultraVIOLET studies support its efficacy and safety compared to other antifungals. If approved, oteseconazole would be the first FDA-approved therapy indicated for the treatment of RVVC.
MedicalResearch.com: What were the most common side effects?
Answer: Oteseconazole was generally safe and well tolerated in all three trials. Treatment-emergent adverse events (TEAEs) were similar across treatment and placebo groups. In the VIOLET studies, related TEAEs were also balanced and included: headache (<1%), nausea (<1%), and diarrhea (<1%). No drug-related severe adverse events (SAEs) were reported.
MedicalResearch.com: Is there potential to utilize oteseconazole in other indications?
Answer: Oteseconazole has also been studied for the potential treatment of onychomycosis, a fungal infection of fingernails or toenails. In a Phase 2 study, oteseconazole met its primary endpoint of complete cure rate at 48 weeks. Oteseconazole led to high nail clearance rates and a favorable safety profile. Oteseconazole exhibits characteristics that appear promising for the treatment of this chronic infection and also for difficult-to-treat opportunistic fungal infections only associated with high mortality.
Mycovia also recognizes a tremendous potential for its oral fungal inhibitors and a growing need to treat a range of multi-drug resistant fungal pathogens. Mycovia is committed to the development of a robust pipeline of novel therapies to address the needs of patients living with overlooked medical conditions in women’s health and beyond.
MedicalResearch.com: When does Mycovia anticipate submitting a new drug application for oteseconazole? Assuming approval, when will Mycovia launch oteseconazole?
Answer: Thankfully, the COVID-19 pandemic didn’t delay our timeframe for oteseconazole, and we appreciate the tireless work of our team at Mycovia and partners in ensuring these clinical trials stayed on schedule. We plan to submit a new drug application for oteseconazole in the first half of 2021. With oteseconazole receiving FDA Qualified Infectious Disease Product Status and Fast-Track designation, we anticipate a U.S. launch in 2021.
MedicalResearch.com: Aside from the U.S., in which other markets are you planning to launch oteseconazole?
Answer: In 2019, Mycovia licensed oteseconazole to Jiangsu Hengrui Medicine Co. to develop and commercialize oteseconazole in China, including mainland China, Hong Kong, Macau and Taiwan, and to Gedeon Richter Plc., a Hungary-based pharmaceutical company, to commercialize and manufacture oteseconazole in Europe, Russia, the Commonwealth of Independent States, Latin America and Australia. The robust interest that the markets have shown over this last year in healthcare and biotech affirms that there is ample capital to support exciting innovations like ours.
Answer: We are thrilled that the positive results from the Phase 3 VIOLET and ultraVIOLET studies bring us another step closer to launching the potential first FDA-approved therapy indicated for the treatment of RVVC. RVVC impacts millions of women, yet the treatment landscape for this global population has been relatively unchanged for decades. Mycovia is at the vanguard for these women as we bring forward an innovative therapy in oteseconazole to address this significant unmet need.
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