New Topical Therapeutic Options in the Management of Superficial Fungal Infections

protein synthesis. In 2014, the FDA approved tavaborole 5% solution for the treatment of toenail onychomycosis.³⁶

Two phase 3, multicenter, randomized, double-blind, vehicle-controlled trials assessed the safety and efficacy of tavaborole in adults with distal subungual onychomycosis, which affected 20% to 60% of a great toenail. The first phase 3 trial included 594 subjects, and the second phase 3 trial included 604 subjects. The subjects were randomized 2:1 to receive tavaborole or vehicle once daily for 48 weeks. The trials’ primary end point was a complete cure of the affected toenail, defined as a mycological cure in addition to a clinically cured toenail at week 52.³⁷ In both studies, the complete cure rate in the tavaborole groups were statistically better than vehicle, 6.5% vs 1% (P<.001) and 9.1% vs 1.5% (P<.001) in studies 1 and 2, respectively.³⁷

The respective incidence of AEs with tavaborole compared with vehicle in the first trial were 64.4% vs 69.9%, and in the second trial were 57.5% vs 54.0%. The vast majority of AEs in patients receiving tavaborole (95.5%) or vehicle (93.4%) were reported as mild or moderate in severity. The most common treatment-related application site AEs with tavaborole in the 2 trials were exfoliation (2.7%), erythema (1.6%), and dermatitis (1.3%).³⁷

Luliconazole was the first antifungal discussed in this article, and it is indicated for the topical treatment of interdigital tinea pedis, tinea cruris, and tinea corporis. A phase 3 trial, evaluating luliconazole for the treatment of interdigital tinea pedis, randomized 321 subjects 1:1 to receive either luliconazole 1% cream or vehicle. The trial’s primary endpoint was complete clearance as defined by both a clinical and mycologic cure, where patients were clear of any clinical signs of erythema, scaling, and pruritus, as well as a negative KOH test and fungal culture. In the trial, 26.4% patients receiving luliconazole 1% cream achieved a complete clearance at day 42, which was 4 weeks after the 2-week treatment period, vs 1.9% patients using the vehicle (P<.001).

A phase 3 trial, evaluating luliconazole 1% cream or vehicle for the treatment of tinea cruris, randomized 483 subjects 2:1 to receive luliconazole 1% cream or vehicle. The primary endpoint was complete clearance at week 3, which was one week post treatment. The primary endpoint was achieved by 21.2% of subjects in the luliconazole group compared with 4.4% in the vehicle group (P<.001). Additionally, 24.4% of patients using luliconazole achieved a clinical cure at day 28 vs 6.6% of patients using the vehicle (P<.001). Moreover, luliconazole was safe and well tolerated in the aforementioned phase 3 studies.

Naftifine hydrochloride cream is FDA-approved for the treatment of tinea pedis, tinea cruris, and tinea corporis; and a 2% gel and cream formulation has recently been FDA-approved for the treatment of interdigital type tinea pedis in pediatric patients aged 12 to 17 years old. In the 2 phase 3 trials reviewed in this article, evaluating naftifine 2% gel for the treatment of moccasin-type tinea pedis, 1,715 subjects were randomized 2:1 to receive naftifine gel 2% or the vehicle. The trials’ primary efficacy variables were a negative mycology culture, which correlated with a complete cure, and scores of 0 on the clinical signs and symptoms for erythema, scaling, and pruritus at week 4 post-treatment. At week 4 post-treatment, 19.6% of the subjects receiving naftifine gel 2% achieved a complete cure vs 0.7% for vehicle-treated subjects (P<.0001). With regards to safety, 1.8% out of 1,143 receiving naftifine gel and 0.7% receiving the vehicle experienced one or more treatment-emergent AEs, but the majority of these subjects continued with the study and completed the trial.

Efinaconazole is a new triazole antifungal indicated to treat onychomycosis caused by T. rubrum and T. mentagrophytes, and it received FDA approval in 2014. Two phase 3 52-week multi-center, randomized, double-blind, vehicle-controlled studies were performed to evaluate the safety and efficacy of efinaconazole 10% solution for the treatment of onychomycosis.

The primary efficacy variable was a complete cure at week 52, which was defined by a clinical cure of the target toenail in addition to a mycologic cure, defined as a negative KOH and negative fungal culture. At week 52, 17.8% of patients in the first study and 15.2% of patients in the second study treated with efinaconazole achieved a complete cure vs 3.3% and 5.5%