VT-1161 is a novel oral agent that we are developing for the treatment of onychomycosis, a very common fungal infection of the nail for which current therapies are suboptimal with respect to safety, tolerability, efficacy and duration of response. We are also developing VT-1161 for recurrent vulvovaginal candidiasis, or RVVC, a common mucosal infection, for which we believe there are no approved therapies in the United States.
VT-1161 has shown high potency and selectivity in in vitro studies and is an orally administered inhibitor of fungal CYP51, a metalloenzyme important in fungal cell wall synthesis. In preclinical studies, VT-1161 has demonstrated broad-spectrum activity against dermatophytes, including the most common species that cause onychomycosis, and against Candida species, including azole-resistant strains, which frequently cause RVVC. Because VT-1161 is highly selective for fungal CYP51, we believe that it may avoid the side effects that limit the use of current antifungals, including terbinafine and fluconazole, which are often prescribed for onychomycosis and acute episodes of vulvovaginal candidiasis, respectively. In addition, due to the high potency and therapeutic index of VT-1161, we believe that the agent may achieve greater efficacy compared to current standard of care therapies for onychomycosis and provide for a highly effective treatment of RVVC.
Onychomycosis is a fungal infection that typically involves the nail matrix, the nail bed, and the nail plate. Approximately 32 million individuals in the United States are afflicted with this condition. According to data provided by IMS Health, approximately 3.0 million prescriptions were written in 2014 for terbinafine, the most commonly used oral drug for onychomycosis. Several new topical agents have also been recently approved and have achieved significant uptake despite the relatively short time period since launch. Despite their significant use, however, current oral and topical agents have significant shortcomings including low cure rates, safety issues and inconvenient dosing. Given the large patient population and the limitations of currently available therapies, we believe that onychomycosis represents a significant commercial opportunity.
RVVC is defined as the occurrence of three or more episodes of acute vulvovaginal candidiasis within a 12-month period. RVVC involves the vaginal mucosa as well as the surrounding tissues and causes a significant negative impact on quality of life and lost days of work. An estimated 5 - 8% of women of child-bearing age are afflicted with RVVC in the United States. While fluconazole or topical therapies are often prescribed to treat each acute episode of vulvovaginal candidiasis in patients with RVVC, we believe that there are currently no approved therapies in the United States to prevent the recurrence of infection. Given the prevalence of this condition, the absence of approved therapies, and the significant negative impact on quality of life for affected women, we believe that RVVC represents a significant commercial opportunity.
We recently completed a randomized, double-blind, Phase 2b clinical trial of VT-1161, the RENOVATE Study, in patients with onychomycosis of the toenail. The study was fully enrolled and patients were randomized to one of four VT-1161 arms or placebo. The treatment arms comprised low or high-dose VT-1161 given once daily during a 14-day loading-dose phase followed by once-weekly administration for an additional 10 or 22 weeks. The placebo arm consisted of a matching placebo regimen.
The RENOVATE study met its primary endpoint of complete cure rates at 48 weeks. In the intent-to-treat analysis, complete cure rates were 0% in the placebo arm compared to a range of 32% to 42% in the four VT-1161 arms of the study with all arms achieving statistical significance vs. placebo. In the per protocol analysis, which includes patients evaluable through week 48, the cure rates were as high as 55% in the VT-1161 groups. There was an 87% median reduction in the percentage of nail involvement at week 48 across the VT-1161 arms, as compared to a 9% reduction in the placebo arm with all arms achieving statistical significance vs. placebo. Complete cure rates continued to improve through week 60, with all active arms having a complete cure rate of greater than 40% in the intent-to-treat analysis. Throughout the study, VT-1161 was very well tolerated with a favorable safety profile. The incidence of adverse events was similar across the VT-1161 arms relative to placebo. No patient in any VT-1161 arm discontinued the study due to a laboratory abnormality and less than 1% of patients across the VT-1161 arms discontinued the study due to an adverse event. There was also no evidence of an adverse effect of VT-1161 on liver function.
We also recently completed a randomized, double-blind, Phase 2b clinical trial of VT-1161, the REVIVE Study, in patients with RVVC. The study was fully enrolled and patients were randomized to one of four VT-1161 arms or placebo. The treatment arms comprised low or high dose VT-1161 given once daily for a seven-day loading-dose phase followed by once-weekly administration for an additional 11 or 23 weeks. The placebo arm consisted of a matching placebo regimen.
The REVIVE study met its primary endpoint of proportion of subjects with one or more culture-verified AVVC episodes through 48 weeks. In the per protocol analysis, which includes patients evaluable through 48 weeks, the recurrence rate in the placebo arm was 66%. In contrast, patients in all VT-1161 arms had markedly lower rates of AVVC recurrence. The proportion of subjects with one or more culture-verified AVVC episodes was 0% to 11% in the four VT-1161 arms of the study with all arms achieving statistical significance vs. placebo. Throughout the study, VT-1161 was very well tolerated with a favorable safety profile, and the incidence of adverse events was lower in all of the VT-1161 arms compared to placebo. In addition, no patient in any VT-1161 arm discontinued the study early due to an adverse event or laboratory abnormality. There was also no evidence of an adverse effect of VT-1161 on liver function.
VT-1161 has received Qualified Infectious Disease Product (QIDP) and Fast Track designations for the treatment of recurrent vulvovaginal candidiasis by the U.S. Food and Drug Administration.