Novel investigational therapies for onychomycosis: an update

ABSTRACT

Introduction: Onychomycosis is an infection of the nail plate that is prevalent among the ageing population. Onychomycosis is difficult to treat with low initial cure rates, high rates of relapse, and reinfection. Present treatment options include oral and topical therapies, with oral therapies yielding better results. However, there has been a greater emphasis on the development of topical antifungal therapies as they have fewer side effects and drug interactions.

Areas Covered: This review summarizes new and reformulated drugs. Results from in vitro studies to Phase III clinical trials are discussed. Novel drugs include: the oral azole VT-1161, the topical azole efinaconazole, the benzoxaborole tavaborole, reformulations of terbinafine P-3058 and LI-P, novel inhibitor of succinate dehydrogenase ME1111, and off-label use of tazarotene. Enhanced permeation of the morpholine amorolfine through the nail plate is also discussed using ultraviolet (UV) curable gels, and a fractional CO₂ laser.

Expert opinion: Novel topical antifungals and the reformulation of current antifungals have demonstrated marked improvement in nail penetration. Current research has an emphasis on topical therapies due to their minimized risk for adverse effects and higher patient demand. Nevertheless, few topical agents have surfaced in the past few years and the investigation of efficacious combination therapies may become more important.

KEYWORDS:

• antifungal
• fungus
• nail
• onychomycosis
• treatment

Article highlights.

• One novel oral azole under development is VT-1161.

• Topical drugs under development are azoles, allylamines, benzoxaboroles, retinoids, morpholines, and succinate dehydrogenase inhibitors.

• VT-1161, P-3058, and ME1111 are currently undergoing clinical investigation.

• Tazarotene was investigated off-label for the treatment of onychomycosis.

• Reformulations to increase permeation through the nail plate were investigated using terbinafine hydrochloride (P-3058 and liposome film formulations) and amorolfine (UV-curable gel).

• Enhancing permeation of drugs through the nail plate is necessary to treat fungal infections in the underlying nail bed.

This box summarizes key points contained in the article.

Financial and Competing Interests Disclosure

AK Gupta has served as a clinical trials investigator and/or speaker for Valeant Pharmaceuticals Inc, Bristol-Myers Squibb, Novartis, Janssen Pharmaceuticals, Bayer Healthcare and Anacor Pharmaceuticals Inc. Furthermore, AK Gupta is the President and CEO of Mediprobe Research Inc., and is also a clinical trials investigator for Mediprobe Research Inc.CD Studholme is employed by Mediprobe Research Inc, which conducts the clinical trials under the supervision of AK Gupta. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.