Fungal Infections
Overview of Albaconazole Javier Bartroli1
and Manuel Merlos2 1. Chief Technology Officer; 2. Chief Scientific Officer, Palau Pharma S.A., Barcelona
Abstract
Albaconazole is a new oral triazole discovered and developed at Palau Pharma with broad-spectrum antifungal activity, unique pharmacokinetics and excellent tolerability. It has demonstrated high in vitro activity against pathogenic yeasts, dermatophytes and filamentous fungi. Albaconazole has proven effective in animal models of systemic aspergillosis, candidiasis, cryptococcosis, scedosporiosis and Chagas’ disease. Preclinical studies did not reveal limiting toxicity concerns. In Phase 1 studies, albaconazole displayed excellent tolerability and high plasma levels with pharmacokinetics suitable for once-weekly administration. In Phase 2 studies, albaconazole showed efficacy superior to fluconazole in vulvocandidiasis after single administration and excellent activity in toenail onychomycosis and tinea pedis when administered once-weekly. Albaconazole has the potential to become a best-in-class drug for the oral treatment of a variety of fungal infections.
Keywords Albaconazole, triazoles, antifungal agents, vulvovaginal candidiasis, onychomycosis, invasive fungal infections, Chagas’ disease, Phase 2
Disclosure: All authors were employees of Palau Pharma at the time of these studies. Received: 25 July 2011 Accepted: 10 August 2011 Citation: European Infectious Disease, 2011;5(2):88–91 Correspondence: Heidi Sisniega, Palau Pharma, S.A., Polígon Industrial Riera de Caldes, Avinguda Camí Reial, 51-57 08184, Palau-solità i Plegamans, Barcelona, Spain. E:
hsisniega@palaupharma.com
Support: The publication of this article was funded by Palau Pharma.
It is clear that the number of fungal opportunistic infections and fungal pathogens has gone up in the last few decades.1
Fungi that were once
considered harmless are now pathogenic in the immunocompromised host. In addition, there is an increase in infections resistant to conventional antifungal therapy. As a result, during the past few decades there has been a rapidly increasing incidence of fungal disease associated with poor therapeutic outcomes.
The armamentarium of newer antifungals available has also risen and may offer new therapeutic options for both regular and emerging pathogens.2
Albaconazole3 (UR-9825; see Figure 1) is a new oral triazole
discovered and developed at Palau Pharma S.A. (Barcelona, Spain) with broad-spectrum antifungal activity, unique pharmacokinetics and excellent tolerability. It has demonstrated high efficacy in Phase 2 clinical trials of vulvovaginitis (single dose), tinea pedis and onychomycosis (once-a-week). As with the rest of the azole class of antifungals, albaconazole inhibits the synthesis of ergosterol, a key fungal cell wall constituent. Its structure carries two chiral centres and it is prepared and developed as a single, pure enantiomer. The current enantioselective synthesis involves only two steps from commercially available compounds.
Satisfactory solid formulations have been obtained in the forms of capsules and tablets. Additionally, cream and lacquer forms are under pharmaceutical development for topical use.
Activity In vitro, albaconazole has shown general superiority when compared with other marketed or investigational azoles such as
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fluconazole, itraconazole, ketoconazole, voriconazole, posaconazole and ravuconazole. This has been reported in different studies involving hundreds of strains of yeasts including Candida albicans, C. parapsilosis, C. guillermondii, C. tropicalis, C. glabrata, C. Krusei, C. dublinensis, C. lusitaniea, C. intermedia, C. holmii, C. kefy, Rhodotorula rubra,4–8
Cryptococcus neoformans,9,10 other basidiomycetous yeasts.13
Similarly, albaconazole has been reported to show excellent activity against filamentous fungi,14 and A. niger,4
A. Ustus,16
including Aspergillus fumigatus,15 A. sclerotiorum,17
Absidia crymbifera,
Alternaria spp., Beauveria spp., Cladosporium spp., Drechslera spp., Emmonsia parva, Fusarium spp., Microsporum spp., Trichophyton spp., Ulocladium spp. and Wangiella dermatiditis,4 Scedosporium spp,19–21
Chaetomium globosum,22
different dermatophytes,23 Fusarium solani,24,25 F. thapsinum,26 S. luriei,30
Paecilomyces spp.,27 and Pseudallescheria boydii.31 active against 70 isolates of Malassezia spp.6
Chagas’ disease is an endemic disease from South America caused by the parasite Trypanosoma cruzi, with a large unmet medical need. Albaconazole has shown high in vitro activity against T. cruzi. The minimum inhibitory concentration (MIC) for albaconazole was 33-fold lower than that of ketoconazole.32–34
The in vivo antifungal efficacy of albaconazole has been demonstrated in a plethora of animal models, including candidiasis, aspergillosis, cryptococcosis, scedosporiosis and trypanosomiasis. Albaconazole
© TOUCH BRIEFINGS 2011 Exophiala spp.,18
a set of 508 strains of F. verticillioides and
Sporothrix schenckii,4,28,29 Albaconazole was also very
C. gattii11,12 and
A. flavus
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