Recently at the American Podiatric Medical Association (APMA) National meeting in Philadelphia, I came across a poster describing the six-month data of a new oral antifungal, VT-1161 (Viamet Pharmaceuticals).1 Currently, this oral medication is undergoing its Phase 2b process and hopefully will start Phase 3 in the new year, but I thought it would be worthwhile to discuss this new medication on the horizon with potential for treating onychomycosis.
When considering an oral antifungal, many physicians and patients alike are concerned with drug-drug interactions and potential liver enzyme elevation/injury. Currently approved medications like itraconazole (Sporanox, Bristol-Myers Squibb) and terbinafine (Lamisil, Novartis) have shown their efficacy in clinical trials, and a meta-analysis looked at the safety of 20,000 patients over 122 studies.2 Even with this data, is it possible to utilize a broad spectrum oral antifungal medication without adversely affecting the liver? This might very well be the case.
The current oral azoles on the market potently inhibit a broad range of human cytochrome p450 enzymes (CYPs), which leads to the issues described above. The new VT-1161 specifically targets fungal CYP51 rather than the related human enzymes.1 Also, the triazole metal binding group has been modified to become a first in its class antifungal: the tetrazole. Preliminary studies found that the minimum inhibitory concentration (MIC) values against mold, dermatophytes and Candida were superior to the approved azoles itraconazole and voriconazole (Vfend, Pfizer). Also, in the Phase I clinical studies, the pharmacokinetics of VT-1161 were favorable and had sustained target tissue concentrations. This explains the dosage regimen used in the Phase 2b study.3
Let’s discuss the current data on VT-1161 for onychomycosis. The Phase 2b multicenter, randomized, double-blind, placebo-controlled, dose-ranging study focused on 259 patients, ranging from 18 to 70 years of age, who had moderate to severe distal subungual onychomycosis (25 to 75 percent nail involvement).1 The current six-month analysis of this study reported the percent change of nail involvement, mycological cure and less than 10 and 25 percent nail involvement. The researchers also included safety assessments of the drug in the study.
In the five arms of this study, patients received a two-week, once daily loading phase of either 300 mg or 600 mg of VT-1161 or placebo.1 The study participants subsequently had once weekly dosing for 10 weeks of either the study drug or continued placebo. Following the initial 12 weeks, patients either received placebo for another 12 weeks or once weekly dosing for another 12 weeks. Accordingly, the total time of taking the medication (active or placebo) for study participants was 24 weeks. At the 24-week point, all the patients stopped taking any oral medication (active or placebo) and there will be a subsequent follow-up at week 60. The average age of the mostly male patients (it is extremely common for most patients to be male in onychomycosis studies) was 48. The mean nail involvement was anywhere from 41.8 to 47.7 percent for the various treatment arms.
So what are the results so far? Those who had received the study drug have attained a median improvement from baseline in percent nail involvement as high as 66.7 percent (300 mg/12 weeks) and 60.8 percent (600 mg/24 weeks).1 Sixty percent of the patients in the 600 g/24-week arm of the study had less than 25 percent nail involvement remaining (i.e. anywhere from 0 to 25 percent nail changes still present clinically) at week 24. Mycological cure (defined as KOH and culture negative for dermatophytes) occurred in 23 to 35 percent of patients across the active medication arms.
What does all of this mean? Well, the 24-week data is promising. Certainly the 48-week and 60-week data are forthcoming and will determine which dosage and length of time of taking the medication the Phase 3 study researchers will use. So far, there has been no evidence of an adverse effect on liver function. Drug-drug interaction data is also forthcoming. Nail involvement change from baseline is also encouraging at the 24-week mark. The potential of this drug to be efficacious and safe as a broad-spectrum antifungal for onychomycosis therapy is exciting.
Watch this space for future updates as it will be interesting to see the antifungal’s progression to end of study and its entrance into Phase 3 studies.
- Tavakkol A, Pollak R, Reyzelman A, et al. A randomized, double-blind, placebo-controlled clinical trial of four oral dosing regimens of VT-1161 in the treatment of patients with moderate-severe toenail onychomycosis (RENOVATE): results of a planned week 24 interim analysis. Poster presentation, American Podiatric Medical Association National, Philadelphia, 2016.
- Chang CH, Young-Xu Y, Kurth T, et al. The safety of oral antifungal treatments for superficial dermatophytosis and onychomycosis: a meta-analysis. Am J Med. 2007;120(9):791–798.
- Hoekstra WJ, Yates CM, Garvey EP, Moore WR, Schotzinger RJ. Rationally-designed metalloenzyme inhibitors have potent, broad-spectrum antifungal activity. Poster presentation, 2012.