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Published online: 14 August 2014
© Springer International Publishing Switzerland 2014
Abstract Tavaborole is a novel, low-molecular weight oxaborole antifungal drug under development by Anacor Pharmaceuticals Inc. for the topical treatment of onychomycosis of the toenail. The drug has received its first global approval for this indication in the US. This article summarizes the milestones in the development of tavaborole leading to this first approval for onychomycosis of the toenails.
1 Introduction
Subungual onychomycosis is difficult to treat due to the poorly perfused location of the infection. To be effective, a topical treatment must penetrate the nail plate and reach the site of infection at a concentration sufficient to exert anti- fungal activity. Tavaborole is a novel, low molecular weight (151.9 Da) oxaborole antifungal drug developed by Anacor Pharmaceuticals, Inc. that has been shown to penetrate the nail after topical application at concentrations sufficient to inhibit the primary causative fungi of ony- chomycosis [1], Tavaborole topical solution 5 % has been approved in by the US Food and Drug Administration (FDA) for the treatment of onychomycosis of the toenails caused by Trichophyton mentagrophytes or Trichophyton rubrum [2, 3], Phase III development in this indication is underway in Canada and Mexico.
1.1 Company Agreements
In early 2007 Anacor entered into an exclusive worldwide licensing agreement with Schering-Plough Corporation (now a subsidiary of Merck) for the development and commercialisation of tavaborole, which led to the two companies successfully manufacturing the product candi- date and completing certain phase III development activi- ties. In February 2010, Merck re tinned full worldwide development and commercialisation rights for the drug to Anacor [4],
1.2 Patent Information
Anacor has been issued patents in the US (US Patent Nos. 7 582 621 and 7 767 657), Australia, New Zealand, South Africa and Russia, which cover, among other embodiments, methods of using tavaborole to treat onychomycosis, and pharmaceutical formulations containing tavaborole.
2 Scientific Summary
2.1 Pharmacodynamics
Tavaborole exerts its antifungal activity by blocking cel- lular protein synthesis via inhibition of yeast cytoplasmic leucyl-aminoacyl transfer RNA (tRNA) synthetase. For- mation of a stable tRNALeu-tavaborole adduct (resulting from the boron atom of the oxaborole ring binding to the 2', 3'-hydroxy groups on the tRNA 3'-terminal adenosine) inhibits leucyl-tRNALeu synthesis, consequentially blocking protein synthesis. Tavaborole analogs...