New Topical Therapeutic Options in the Management of Superficial Fungal Infections

of action is unknown, the drug appears to inhibit activity of the enzyme lanosterol 14α-demethylase, which prevents conversion of lanosterol to ergosterol, a necessary constituent of the fungal cell wall.¹⁷

Pre-clinical data demonstrated strong antifungal activity of luliconazole. In one study, the drug demonstrated potent mean inhibitory concentrations against both T. rubrum and E. floccosum.¹⁸ While the clinical significance of this data has not been established, these organisms are the most common causes of tinea pedis, tinea corporis, and tinea cruris. In an in vivo study, luliconazole was demonstrated to be maintained at high levels in the stratum corneum over 14 days. Here, the drug was topically applied to guinea pig plantar skin, and the stratum corneum was evaluated for drug levels. After application for 3 consecutive days, high levels of luliconazole were observed and maintained over the 14-day course of the study with continued daily application.¹⁹

Two phase 3 clinical studies have been published evaluating the safety and efficacy of luliconazole in tinea pedis and tinea cruris. In total, 324 eligible patients used luliconazole—159 in the tinea pedis study and 165 in the tinea cruris study.^20,21

This randomized, double blind, vehicle controlled study was performed across 12 U.S. study sites to evaluate the safety and efficacy of luliconazole for interdigital tinea pedis. Three hundred and twenty-one subjects eligible for the modified intent-to-treat analysis were randomized 1:1 to receive either luliconazole 1% cream (n=159) or vehicle (n=162). They applied the study drug once daily for 2 weeks, followed by 4 weeks of follow-up. Patients were 12 years of age or older, and suffered from at least moderate disease. Baseline demographics as well as signs and symptoms of erythema, scaling, and pruritus were equally distributed in both arms of the respective studies.²¹

The study’s primary endpoint was complete clearance at the 4-week post-therapy time point. Complete clearance was defined as both a clinical and mycologic cure, where patients were clear of any clinical signs of erythema, scaling, and pruritus along with a negative potassium hydroxide (KOH) test and fungal culture. Statistically significant differences in complete clearance were achieved in the active vs vehicle arm (P<.001). 26.4% patients on luliconazole 1% cream achieved a complete clearance at day 42 (4 weeks after the 2-week treatment period), compared with 1.9% patients using the vehicle (P<.001).²¹

The studies met all of its secondary efficacy end points. 62.3% of patients in the luliconazole group and 17.5% in the vehicle group achieved a mycological cure (defined as both a negative KOH and fungal culture) at the 4-week post-treatment visit. Similarly, statistical significance was achieved in evaluating the clinical cure at the 4-week post-treatment visit (29.2% vs 7.8% in the luliconazole and vehicle groups, respectively, P<.001). Here, clinical cure was defined as the absence of any signs of erythema and scaling along with zero patient-reported pruritus.²¹

An “effective treatment” was a secondary endpoint defined as achieving both a mycologic cure along with a clinical improvement of no pruritus but at most mild erythema and/or scaling at the 4-week post-treatment visit. This hybrid endpoint represents a real-world scenario of those patients who have been cured of the infection but who have not yet fully recovered clinically. The pooled results from both studies of patients who reached this endpoint were 48.1% and 9.7% in the luliconazole cream and vehicle group respectively (P<.001).²¹

In the phase 3 study evaluating tinea cruris, participants applied luliconazole cream once daily for a week, with follow-up for 3 weeks post-therapy (day 28). Four hundred and eighty-three patients were enrolled, and those eligible for the modified intent-to-treat analysis were randomized 2:1 to receive either luliconazole 1% cream (n=165) or vehicle (n=91). Eligible patients were at least 12 years old and had a tinea infection with signs of at least moderate erythema, mild scaling, and moderate pruritus. Baseline demographics and disease signs and symptoms were evenly matched between treatment groups.²⁰

The primary and secondary endpoints of the tinea cruris study mirrored those of the tinea pedis studies, and all endpoints were met. The primary endpoint of complete clearance at the 3 weeks post one-week treatment was 21.2% in the luliconazole group vs 4.4% in the vehicle group (P<.001). A mycological cure at that day 28 visit was achieved by 78.2% and 45.1% of