A topical 10% efinaconazole solution was significantly more effective than was placebo against mild to moderate onychomycosis in a pair of randomized, controlled phase III studies comprising more than 1,000 patients.
Current topical therapies for distal lateral subungual onychomycosis (DLSO) are lacquer based, and require nail debridement and the removal of lacquer residue, said Dr. Boni Elewski of the University of Alabama, Birmingham, and her colleagues.
"Oral treatment is limited by drug interactions and risk of acute liver injury (requiring laboratory monitoring)," the researchers noted.
Dr. Boni E. Elewski
To test the efficacy of topical efinaconazole 10%, 1,655 adults with onychomycosis were randomized in two studies (study 1: 870 patients, study 2: 785 patients) at 118 sites in the United States, Canada, and Japan. In both studies, the mean area of target toenail involvement was approximately 36%, with an average of 2.8 affected nontarget toenails per patient. Demographic characteristics were not significantly different between the treatment and placebo groups in either study.
Overall, 18% and 15% of efinaconazole patients in study 1 and study 2, respectively, met the primary endpoint of complete cure at 52 weeks, compared with 3% and 6% of placebo patients, respectively. In addition, 55% and 53% of treatment patients in the two studies met the secondary endpoint of mycologic cure, compared with 7% of placebo patients in each study. Both complete cure and mycologic cure rates were in the range of cure rates achieved with oral therapies, the researchers noted.
The average age of the patients in studies 1 and 2 was 52 years and 51 years, respectively, and approximately 75% of the participants in both studies were men. Patients in each study were randomized to a topical solution of 10% efinaconazole or a placebo vehicle, self-applied at home once daily for 48 weeks. Patients were assessed at 12-week intervals during the study period, and reexamined at 52 weeks after a 4-week treatment-free period. The findings were published in the Journal of the American Academy of Dermatology (2013;68:600-8).
Overall, the rate of adverse events was similar between the drug and placebo groups. Efinaconazole was not associated with adverse events including redness, swelling, burning, itching, or vesiculation, and localized skin reactions were similar between the groups. A total of 235 patients discontinued the study early; the main reasons were patient request (98), lost to follow-up (78), and adverse events (33).
The study was limited by its specific patient population, which did not include children or those with severe disease, the researchers noted. Efinaconazole has not yet been studied in combination with oral antifungal treatment. But the findings suggest that topical efinaconazole is safe and effective, and "may be the first topical treatment for DLSO that can be considered a viable alternative to oral treatments," the researchers wrote.
Dr. Elewski has served as an adviser to Valeant Dermatology, a division of Valeant Pharmaceuticals, which funded the study and manufactures efinaconazole. Her coauthors disclosed that they were employees and stockholders of, and/or advisers and consultants to, several pharmaceutical companies, including Valeant.
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