Drug Developments in Onychomycosis
It has been a while since any new drugs have entered the market indicated for the treatment of onychomycosis. In an earlier blog I discussed some topical antifungal drugs which were not available in the UK (click here) but a paper late last year reports a potential new, oral agent that has completed phase 2 clinical trials. Drug trials are normally conducted in three phases:
Phase 1: Normally a drug tested on healthy volunteers to determine safety and its effective dosing ranges.
Phase 2: Tests of a product normally as a controlled trial to assess the drug’s effectiveness and continued safety, which intensively studies participants with the condition under study.
Phase 3: A larger study on a broader population with the condition and usually compares the new product with existing ones.
Phase 4: A drug, following approval for use, undergoes post-marketing surveillance to ensure continued safety and effectiveness.
A new antifungal product with the code name VT-1161 finished its phase 2 clinical trials with results being published in the British Journal of Dermatology . The drug works as a cytochrome P51 (CYP51) inhibitor with potent in vitro activity against several species of tinea and yeasts.
The randomized controlled trial of 259 patients was aimed specifically at assessing the drug’s safety as well as testing 5 different dosing regimens to assess which showed the most effectiveness. At the end of the study at week 48, none of the placebo group had shown a complete cure versus between 32%-42% of the active treatment groups.
Do we need another oral agent? At this stage, the drug is showing promise but it is entering a market currently dominated by itraconazole and terbinafine. So, does it have any distinct advantages over the existing dynamic duo? Well, there are a few things to note which may make a difference. Firstly, safety. There were just 6% adverse events reported in the treatment arm and they were classified as mild to moderate – ingrowing toenail, headache and cough although the frequency of these were similar in the placebo group as well. Data so far has not shown any adverse effects on liver function with VT-1161, which has been an issue observed with terbinafine which I covered in a previous blog (click here).
Secondly, the new drug could be used at a lower dosing regimen – potentially a once-a-week dose, which represents a significant advantage over terbinafine and even the “pulsed” regime of itraconazole . Finally, while the cure rate result may seem low at 32% - 42% it is important to remember that this is a complete cure (namely negative mycology plus restoration of the visual appearance to normal). The mycological cure rates (negative microscopy including negative culture) was 72% which shows rates comparable to terbinafine and itraconazole. Further analysis showed that the improvement in the percentage of nails involved was as high as 92% at 48 weeks versus just 14% in the placebo group - a very promising result. As a final thought with new reports of terbinafine resistant dermatophytes strains emerging in parts of the world, new classes of antifungals will be needed in the pipeline to prevent issues around drug resistance - this is a topic that will be covered in a forthcoming blog.
Ultimately, if the drug is likely to be approved it will need to complete phase three trials which test it in a broader population for efficacy and safety. The results of the trials to date suggest a potential competitor for the oral antifungal agents currently available. If it does reach the approval stage, of course, in what countries the drug will be licensed and available is currently unknown.
1. Elewski B, Brand S, Degenhardt T, et al. A phase II, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the efficacy and safety of VT-1161 oral tablets in the treatment of patients with distal and lateral subungual onychomycosis of the toenail. Br J Dermatol. 2020. Online ahead of print.
2. Gupta AK, Gover MD, Lynde CW. Pulse itraconazole vs. continuous terbinafine for the treatment of dermatophyte toenail onychomycosis in patients with diabetes mellitus. J Eur Acad Dermatol Venereol. 2006;20(10):1188-1193.