A Closer Look At A New Topical Option For Onychomycosis

Limited pharmacologic treatment options exist for onychomycosis, especially for patients who wish to avoid or are unable to take oral antifungal medication. Ciclopirox 8% nail lacquer (Penlac) has long been the only prescription strength, Food and Drug Administration (FDA) approved topical antifungal for the treatment of onychomycosis. Unfortunately, ciclopirox 8% nail lacquer has had very poor therapeutic outcomes, even with concomitant nail debridement. Over the past 10 years, following the introduction of topical ciclopirox 8% nail lacquer, there has been a significant lack of development of topical antifungal therapies for the treatment of onychomycosis.

Recently, efinaconazole 10% solution (Jublia, Valeant Pharmaceuticals) has emerged as a promising new prescription strength topical treatment option for onychomycosis. Efinaconazole reportedly has cure rates comparable to oral itraconazole (Sporanox, Janssen Pharmaceuticals) and mycological and complete cure rates two to three times greater than that of ciclopirox 8% nail lacquer.¹

Nail debridement has been an integral part of therapeutic studies examining the efficacy of ciclopirox. Despite concomitant nail debridement, the efficacy of ciclopirox for the treatment of onychomycosis is very poor. Daily application of ciclopirox 8% nail lacquer in combination with nail debridement has shown mycological cure rates (negative culture and negative potassium hydroxide preparation) ranging from 29 to 36 percent.^2,3 Complete cure rates (mycological cure and normal toenail appearance) of ciclopirox 8% nail lacquer are significantly lower, ranging from 5.5 to 8.5 percent.³ Given these outcomes, physicians usually reserve ciclopirox for very mild cases of onychomycosis, for palliative care, when patients cannot tolerate oral antifungal medication or when oral antifungals are contraindicated.³

How Efinaconazole 10% Solution Compares To Other Antifungals For Onychomycosis

Efinaconazole 10% solution, a new triazole topical antifungal specifically developed for onychomycosis, received FDA approval in June. Two parallel, double-blind, randomized phase III trials, — in which study participants applied efinaconazole daily for 48 weeks without nail debridement — showed mycological and complete cure rates two to three times greater than those for ciclopirox, and comparable to 12 weeks of oral itraconazole.^1,3-5 Specifically, efinaconazole showed a 53.4 to 55.2 percent mycological cure rate at 52 weeks.^4,5 The complete cure rate with efinaconazole treatment was 15.2 to 17.8 percent. In these studies, researchers considered 40 to 45 percent of patients as having treatment successes. They defined treatment success as an affected target toenail area of less than 10 percent.

Several factors, including the topical’s antifungal and physiochemical properties, theoretically contribute to the much higher efficacy of efinaconazole 10% solution. Efinaconazole is a broad spectrum antifungal with in vitro studies showing activity against dermatophytes, non-dermatophytes and yeast. Researchers have shown that efinaconazole is more potent than terbinafine, ciclopirox, itraconazole and amorolfine in in vitro testing against T. rubrum, T. mentagrophytes, Candida albicans and Epidermophyton floccosum.⁶

Physicochemical properties that contribute to the efficacy of efinaconazole 10% solution include improved nail unit penetration and distribution to the entire nail apparatus. Nail unit penetration is a primary limiting factor for topical antifungal medications. Keratin binding and the rate of keratin bound drug release are important factors in allowing topical antifungals to penetrate the nail plate and exert their antifungal activity at the deeper levels of the nail plate, the nail bed and the nail matrix.¹

Research has shown efinaconazole 10% solution to have considerably lower keratin binding and faster keratin bound drug release in comparison to other topical antifungals.¹ Alcohol, lipophilic esters and cyclomethicone in the efinaconazole solution help to create a low surface tension that allows application to the dry nail surface, nail folds, hyponychium and the undersurface of the nail, improving drug delivery and distribution.¹ To date, researchers have evaluated the therapeutic efficacy of efinaconazole 10% solution without additional nail plate debridement. The hypothesis is that debridement may increase nail plate penetration and lead to even higher mycological and complete cure rates.

In Conclusion

Onychomycosis can be a difficult disorder to treat, especially in patients who cannot tolerate or are not candidates for oral antifungal medications. Until recently, topical treatment options were very limited with ciclopirox 8% nail lacquer being the only prescription topical antifungal available for the treatment of onychomycosis. Efinaconazole 10% solution is a promising new topical treatment option of onychomycosis with cure rates comparable to oral itraconazole, and mycological and complete cure rates 2 to 3 times greater than that of ciclopirox 8% nail lacquer.

References

1. Del Rosso JQ. The role of topical antifungal therapy for onychomycosis and the emergence of newer agents. J Clin Aesthet Dermatol. 2014;7(7):10-8.

2. De Berker D. Fungal nail disease. N Engl J Med. 2009;360(20):2108210800

3. Gupta AK, Joseph WS. Ciclopirox 8% nail lacquer in the treatment of onychomycosis of the toenails in the United States. J Am Podiatr Med Assoc. 2000;90(10):495495 2

4. Elewski BE, Rich P, Pollak R, et al. Efinaconazole 10% solution in the treatment of toenail onychomycosis: Two phase III multicenter, randomized, double-blind studies. J Am Acad Dermatol. 2013;68(4):600-8.

5. Gupta AK, Elewski BE, Sugarman JL, et al. The efficacy and safety of efinaconazole 10% solution for treatment of mild to moderate onychomycosis: a pooled analysis of two phase 3 randomized trials. J Drugs Dermatol. 2014;13(7):815-20.

6. Jo Siu WJ, Tatsumi Y, Senda H, et al. Comparison of in vitro antifungal activities of efinaconazole and currently available antifungal agents against a variety of pathogenic fungi associated with onychomycosis. Antimicrob Agents Chemother. 2013;57(4):1610-6.