Onychomycosis armamentarium set to expand with new options

April 1, 2014

Oral terbinafine has been the gold standard for treatment of onychomycosis for more than 20 years, but development of new therapeutic options has been the focus of some significant research activity.

Maui, Hawaii - Oral terbinafine has been the gold standard for treatment of onychomycosis for more than 20 years, but development of new therapeutic options has been the focus of some significant research activity.

Speaking at MauiDerm 2014, Aditya K. Gupta, M.D., Ph.D., professor of dermatology, University of Toronto, Ontario, and President, Mediprobe Research, London, Ontario, provided an update on emerging treatments for onychomycosis.

Oral options

Dr. Gupta notes that two new oral triazole antifungal agents - posaconazole (Noxafil, Merck) and albaconazole (Stiefel) - are being investigated for the treatment of onychomycosis. Results from dose-ranging clinical trials showed that using the most effective dose (posaconazole 200 mg/day for 24 weeks, albaconazole 400 mg/day for 36 weeks), both agents were associated with a mycological cure rate similar to that achieved using a pulse terbinafine regimen. However, the new antifungal agents had lower complete cure rates than that associated with terbinafine.

“It remains to be seen what role these new oral antifungal agents would have in the management of onychomycosis. Perhaps they will be considered as monotherapy for mild to moderate onychomycosis or maybe they will be used part of a combination regimen,” Dr. Gupta says.

Topical therapy

Dermatologists can also look forward to an expansion of the armamentarium of topical treatments for onychomycosis.

Efinaconazole 10 percent solution (Jublia, Valeant Pharmaaceuticals) was recently approved in Canada for the treatment of onychomycosis. Features of this triazole antifungal include potent in vitro activity against dermatophytes, yeasts and nondermatophytes along with relatively low keratin binding. Phase 3 studies investigating once-daily treatment with efinaconazole showed that at 52 weeks, mycological and complete cure rates were 54 and 17 percent, respectively, exceeding the outcomes reported for topical ciclopirox (32 and 7 percent, respectively).

Tavaborole (Anacor) is also being developed as a topical treatment for onychomycosis. It is a broad-spectrum oxaborole antifungal agent that has a low molecular weight and low lipophilicity, features that facilitate penetration into the nail plate. In preliminary clinical testing, patients who applied tavaborole 5 percent topical solution once daily for 48 weeks to affected toenails achieved mycological and complete cure rates of 34 percent and 8 percent, respectively, according to press release data from Anacor.

“When reviewing the results achieved with efinaconazole and tavaborole, it is important to recognize there were methodological differences between the studies that preclude making head-to-head comparisons of the two medications. In addition, the efinaconazole vehicle was twice as effective as the tavaborole vehicle,” Dr. Gupta says.

Another topical imidazole antifungal, luliconazole 10 percent solution, is in phase 2/3 studies for the treatment of onychomycosis. A 1 percent cream formulation of luliconazole (Luzu, Valeant) was recently approved by the Food and Drug Administration (FDA) for the treatment of interdigital tinea pedis, tinea cruris and tinea corporis.

Dr. Gupta notes that topical antifungal treatments are less effective than systemic therapies, but they can be a useful alternative in patients who are not good candidates for one of the oral medications. In addition, he speculates that the new topicals may have a role for treating patients who fail oral therapy and that their efficacy might be improved by lengthening the course of treatment from 12 months to at least 18 months. Consideration might also be given to using topical therapy as early prevention against infection recurrence, which is a very common problem.

 

 

Lasers for onychomycosis

Several lasers have received 510(k) FDA clearance to be marketed for use in treating onychomycosis. However, Dr. Gupta points out that the approved indication for these devices is cosmetic in nature, ie., use for the temporary increase of clear nail, and can be granted based on demonstration of equivalency to predicate devices.

“I think the jury is still out on the use of lasers for onychomycosis. We have a lot to learn about their mechanism and the effects of different wavelengths, and we need data from randomized controlled trials evaluating their efficacy for achieving complete and mycological cures,” he says.

Strategies for improving outcomes

Success in treating onychomycosis depends on accurate diagnosis, and Dr. Gupta notes that molecular biology diagnostic techniques that have recently become available are a major step forward for determining the causative pathogen(s), especially considering the likelihood of a mixed infection.

He also reminds dermatologists that effective treatment of onychomycosis and preventing recurrence requires attention to reducing the fungal burden in shoes and socks. Disinfection by laundering requires washing in hot water exceeding 60 degrees Celsius for longer than 45 minutes. Ozone and ultraviolet light devices have also been shown effective for sanitizing shoes.

Disclosures: Dr. Gupta has been a clinical trial investigator or speaker for multiple companies that market treatments for onychomycosis.