Review of the Clinical Efficacy and Safety of Efinaconazole 10% Topical Solution for Onychomycosis Across Subgroups

Abstract

Introduction: Onychomycosis treatment can be challenging, and factors like disease severity and age can affect treatment response. Topical efinaconazole 10%—approved in 2014 in the US for once-daily toenail onychomycosis treatment—demonstrated efficacy and safety in 2 identical pivotal phase 3 trials and several post hoc analyses (eg, patient sex, age, etc). This review summarizes efinaconazole efficacy/safety data in different subgroups from published phase 3 post hoc analyses.

Methods: A literature search was performed to identify post hoc analyses of the 2 efinaconazole phase 3 trials (NCT01008033; NCT01007708), in which participants 18-70 years of age with mild to moderate toenail onychomycosis (20%-50% clinical involvement; N=1655) were randomized (3:1) to once-daily efinaconazole/vehicle (VEH) for 48 weeks, with 1 follow-up at week 52. Efficacy endpoints at week 52 included rates of mycologic cure (MC; negative potassium hydroxide examination + negative fungal culture), complete cure (0% clinical involvement + MC), and complete/almost complete cure (≤5% clinical involvement + MC). Adverse events (AEs) were also assessed.

Results: A total of 25 subgroups were examined in 9 post hoc analyses: sex (male/female; 2 analyses), age (<65/≥65 years; ≥65 only), weight (<84.4/≥84.4 kg), self-reported race (White/Asian/Black) or ethnicity (Latino/non-Latino), baseline disease severity (mild/moderate; 2 analyses) or duration (1-5/>5 years), concurrent tinea pedis (no/yes), concurrent treated tinea pedis (no/yes), or concurrent diabetes (yes). All 9 analyses (25 subgroups) reported complete cure rates for efinaconazole vs VEH, with ranges of 12.9%-29.4% vs 0%-13.0%, respectively, which were generally similar to the overall phase 3 populations (15.2%-17.8% vs 3.3%-5.5%, respectively). Eight analyses reported MC (17 subgroups) and complete/almost complete cure (14 subgroups) for efinaconazole vs VEH, with ranges of 45.2%-64.8% vs 10.7%-30.4% and 19.1%-37.5% vs 0%-18.8%, respectively; rates were generally similar to the overall populations (MC, 53.4%-55.2% vs 16.8%-16.9%; complete/almost complete cure, 23.4%-26.4% vs 7.0%-7.5%). AE and discontinuation rates with efinaconazole ranged from 54.3%-71.3% (5 analyses, 9 subgroups) and 0%-5.5% (6 analyses, 11 subgroups), respectively, and were in line with the overall populations (AEs, 64.5%-66.0% vs 58.5%-61.0%; discontinuations, 1.9%-3.2% vs 0%-0.5%).

Conclusions: Once-daily topical efinaconazole 10% solution demonstrated efficacy and safety that was comparable to the overall phase 3 trials in multiple patient populations with onychomycosis, including those who may be more difficult to treat, such as older patients and those with greater disease severity.