Background Onychomycosis, a fungal nail infection, can impact quality of life. Objective We sought to evaluate the efficacy and safety of tavaborole topical solution, 5% for treatment of toenail ...onychomycosis. Methods In 2 phase-III trials, adults with distal subungual onychomycosis affecting 20% to 60% of a target great toenail were randomized 2:1 to tavaborole or vehicle once daily for 48 weeks. The primary end point was complete cure of the target great toenail (completely clear nail with negative mycology) at week 52. Secondary end points included completely or almost clear nail, negative mycology, completely or almost clear nail plus negative mycology, and safety. Results Rates of negative mycology (31.1%-35.9% vs 7.2%-12.2%) and complete cure (6.5% and 9.1% vs 0.5% and 1.5%) significantly favored tavaborole versus vehicle ( P ≤ .001). Completely or almost clear nail rates also significantly favored tavaborole versus vehicle (26.1%-27.5% vs 9.3%-14.6%; P < .001). Rates of completely or almost clear nail plus negative mycology (15.3%-17.9% vs 1.5%-3.9%) were significantly greater for tavaborole versus vehicle ( P < .001). Application-site reactions with tavaborole included exfoliation (2.7%), erythema (1.6%), and dermatitis (1.3%). Limitations Duration of follow-up is a limitation. Conclusion Tavaborole demonstrates a favorable benefit-risk profile in treatment of toenail onychomycosis.
Summary
Background
Onychomycosis is a fungal disease that affects the fingernails and toenails and is predominantly caused by dermatophytes. VT‐1161 is a novel inhibitor of fungal CYP51 through the ...inhibition of lanosterol demethylase, and has demonstrated potent activity against Trichophyton rubrum and Trichophyton mentagrophytes.
Objectives
To evaluate the safety and efficacy of four dosing regimens of orally administered VT‐1161 compared with placebo in patients with moderate‐to‐severe distal and lateral subungual onychomycosis of the toenail.
Methods
This was a phase II, randomized, double‐blind, placebo‐controlled, multicentre study (ClinicalTrials.gov identifier NCT02267356). Patients aged 18–70 years (n = 259) who had 25–75% mycotic involvement were randomized to five treatment groups. They received 300 mg VT‐1161 as a 2‐week daily dose, followed by a once‐weekly dose for either 10 or 22 weeks, or 600 mg VT‐1161 as a 2‐week daily dose, followed by a once‐weekly dose for either 10 or 22 weeks. All treatments were followed by a nontreatment period of 36 weeks. A matching placebo arm was included.
Results
In the intent‐to‐treat population, at week 48 the complete cure rates were 0% in the placebo group and ranged from 32% to 42% in the VT‐1161 treatment groups (P < 0·001 vs. placebo). VT‐1161 was well tolerated, with no evidence of an adverse effect on liver function or QT intervals.
Conclusions
VT‐1161 treatment led to high nail clearance rates and a favourable safety profile. VT‐1161 exhibits characteristics that appear promising for the treatment of this chronic and difficult‐to‐treat condition and warrants further evaluation in larger studies.
What is already known about this topic?
Onychomycosis is a fungal disease that is chronic and difficult to treat.
Topical drugs are currently available but have limited effectiveness. Oral drugs, while effective, suffer from side‐effects including liver function abnormalities.
The majority of patients are elderly on polypharmacy and are at high risk of drug interactions.
An effective and safe oral drug with low potential for liver toxicity and drug interaction is highly desirable.
What does this study add?
This study presents the first large phase II study of a novel tetrazole antifungal, VT‐1161.
The study shows that VT‐1161 has an encouraging safety profile and is highly effective in treating even hard‐to-treat cases of onychomycosis.
The new tetrazole provides a lower overall drug load with an excellent safety and tolerability profile.
VT‐1161 is as effective as or numerically better than the current standard of care, terbinafine.
Linked Comment: Barbieri. Br J Dermatol 2021; 184:191.
Plain language summary available online
Typically, the amount of mycotic nail involvement in onychomycosis (fungal infection of the nail) before and after drug therapy is determined visually. Because there is an inherent element of ...subjectivity, it is difficult to accurately measure and compare results across clinical trials or to assess how much improvement has been achieved in response to therapy. We developed a simple tool for measuring mycotic nail involvement. This novel tool consists of a large grid containing 5 toenail templates of varying nail morphologies that are derived from the actual shape of the toenail of the great toe in several males and females, and one standardized computer-generated nail shape. The toenail templates are presented in 7 different sizes to match different nail sizes. Each toenail template is further divided into 8 segments, each comprising approximately 12.5% of the total nail surface. Measurement of the percentage of mycotic nail involvement is accomplished by the following procedure: (1) placing tracing film over the target toenail; (2) tracing the outline of the entire toenail, followed by tracing the affected portion of the toenail on the same film; (3) placing the tracing film over a nail template on the grid that best fits the shape of the toenail; and (4) counting the number of grid segments that correspond to 50% or more involvement. To assess feasibility, the tool was used in a large randomized trial involving over 30 sites and 500 subjects with onychomycosis. This tool is a more accurate and less biased alternative to visual assessment for measuring nail involvement or progression of nail clearing.
PDF
