Drugs currently under investigation for the treatment of invasive candidiasis

ABSTRACT

Introduction: The widespread implementation of immunosuppressants, immunomodulators, hematopoietic stem cell transplantation and solid organ transplantation in clinical practice has led to an expanding population of patients who are at risk for invasive candidiasis, which is the most common form of fungal disease among hospitalized patients in the developed world. The emergence of drug-resistant Candida spp. has added to the morbidity associated with invasive candidiasis and novel therapeutic strategies are urgently needed.

Areas covered: In this paper, we explore investigational agents for the treatment of invasive candidiasis, with particular attention paid to compounds that have recently entered phase I or phase II clinical trials.

Expert opinion: The antifungal drug development pipeline has been severely limited due to regulatory hurdles and a systemic lack of investment in novel compounds. However, several promising drug development strategies have recently emerged, including chemical screens involving Pathogen Box compounds, combination antifungal therapy, and repurposing of existing agents that were initially developed to treat other conditions, all of which have the potential to redefine the treatment of invasive candidiasis.

KEYWORDS:

• Candidiasis
• glucan synthase
• chitin
• SCY-078
• mycoses

Article highlights

• Invasive candidiasis (IC) is the most common fungal disease among hospitalized patients in the developed world and comprises both bloodstream infection due to Candida spp. and deep-seated tissue candidiasis

• In 2016, nosocomial transmission of C. auris, which was previously a rare cause of IC, led to a worldwide outbreak associated with distinct clonal lineages

• Only one new class of antifungal agents has been introduced into clinical practice in the past three decades

• The Pathogen Box is a project led by Medicines for Malaria Venture (MMV, Switzerland) that aims to identify novel drugs with activity against diseases such as tuberculosis, malaria, toxoplasmosis, and hemorrhagic viral infections

• AR-12 is in the early stages of development as a drug to treat IC, but it shows remarkable promise due to its activity against azole- and echinocandin-resistant Candida isolates

• AR-12/OSU-03012 is a celecoxib-derivative inhibits fungal acetyl CoA synthetase in vitro and is fungicidal at concentrations similar to those achieved in human plasma

• The mammalian PDK1 inhibitor KP-372–1 is a potent antifungal agent with activity against Candida spp. that was identified using a screening strategy for PKIs that block the cell wall stress response in yeast

• SCY-078 (formerly MK-3118) is novel oral glucan synthase inhibitor and represents the first compound of the triterpene class of antifungals

This box summarizes key points contained in the article

Declaration of interest

M. W. McCarthy has served as a paid consultant to Allergen. T. J. Walsh receives research grant for the experimental and clinical antimicrobial pharmacotherapeutics from Astellas, Cubist, Theravance, The Medicines Company, Allergan, Novartis, Merck and Pfizer. He has also served as a consultant to Astellas, Actavis, ContraFect, Drais, iCo, Novartis, Methylgene, SigmaTau and Trius. 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.

Additional information

Funding

This manuscript was not funded.