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Anti-Fungal Drugs- Something New and Something Old

Invasive, life threatening fungal diseases are a major cause of mortality and morbidity. The number of therapeutic options available for treating invasive fungal infections is quite limited compared to bacterial infections; and they include only three structural classes of drugs, polyenes, azoles and echinocardins. Polyenes which are the oldest class of antifungal drugs has a major drawback attributed to them i.e. their toxicity. However, over the past 30 years, anti-fungal drugs have been given a great deal of importance and research in the field had increased dramatically.

Anti-fungal drugs have their applications in the treatment of invasive fungal infections such as Aspergillosis, Candidiasis, Cryptococcosis and Febrile neutropenia. Invasive Candidiasis is a common healthcare-associated infection. It is estimated that approximately 46,000 cases of invasive candidiasis occur each year in the United States.  Candidemia is the most common of invasive candidiasis. Overall candidemia rates have increased over the past 20 years, according to a survey conducted by CDC the incidence rate per 100,000 persons increased from 9.1 during 1992-1993 to 14.1 in 2008 in Atlanta region whereas it increased from 24.2 during 1998-2000 to 30.9 in 2008 in Baltimore region. Rates have decreased since 2008 with the improvements in the field of antifungal drugs.

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In contrast to the development of new antimicrobials targeting bacteria, antifungal drug development faces a key challenge that the fungal pathogens are closely related to the host. Most of the small molecules that affect the yeast will also affect humans subsequently. Hence targeting the structures unique to fungi has been a major challenge in the development of these drugs. In the last 2 decades, treatment options for the systemic fungal infections have expanded substantially, with the introduction of 3 lipid-based amphotericin B preparations, 4 azole antifungal drugs, and an echinocardin. These new agents are less toxic and in some cases, more efficient than amphotericin B deoxycholate, which was the gold standard of antifungal therapy for decades.

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Historically, the most common approach for identifying antifungal small molecules has been to screen large number of synthetic or natural products for their ability to inhibit the growth of a selected fungus. It is impossible to predict which of the lead molecules currently being explored will emerge as the next clinically useful antifungal.

Anti-Fungals in Clinical Development

Drug Candidate

Company/ Organization

Targeted Disease

Preclinical Stage

Aminocandin

Novexel, France

First line therapy against invasive fungal infections

Novamycin

Novabiotics Ltd., UK

Bloodstream and deep tissue infections caused by Candida

Phase 1 Clinical Trial or Completed

Recombinant Protein Vaccine (NDV-3)

NovaDigm Therapeutics, Inc., USA

Recurrent Vulvovaginal Candidiasis

Virosome Formulated Anti-Candida Vaccine (PEV7)

Pevion Biotech Ltd, Switzerland

Being developed for recurrent Vulvovaginal Candida infection

Nikkomycin Z

University of Arizona, USA

Treatment of patients with uncomplicated Coccidioides pneumonia

Phase II trial in progress or completed

VT-1161 (Oral)

Viamet Pharmaceuticals, Inc., USA

Acute vulvovaginal candidiasis

Luliconazole

Topica Pharmaceuticals, USA

Distal subungual onychomycosis

MOB015

Moberg Derma AB, Sweden

Distal subungual onychomycosis

Human lactoferrin hLF1-11

AM-Pharma, The Netherlands

Infectious complications among haematopoietic stem cell transplant recipients

Albaconazole

Stiefel (GlaxoSmithKline company), USA

Distal subungual Onychomycosis

Novexatin

Novabiotics Ltd., UK

topical brush-on treatment for onychomycosis

Phase III trial in progress or completed

Isavuconazole

Astellas Pharma Inc., Japan and Basilea Pharmaceutica, Switzerland

Treatment of Candidemia and other invasive Candida infections

Glucocorticoid

Postgraduate Institute of Medical Education and Research, India

Allergic bronchopulmonary Aspergillosis

 

The global burden of fungal disease is noteworthy as a number of investigators have been underappreciated or underfunded relative to other diseases. Currently, the gold standard therapy for cryptococcosis, one of the most prevalent invasive life threatening fungal infections on the planet, is based on the drugs that were developed in the 1950s. Since the introduction of amphotericin, only two additional classes of antifungals have been developed. This rate of antifungal drug discovery is unlikely to be meeting the future demands.

To find out more on the Anti-Fungal drugs in the healthcare domain, checkout Market Data Forecast’s comprehensive research report “Global Anti-Fungal Drugs” equipped with exhaustive segmentation, wide ranging geographical analyses complete with list of the drivers and restraints, company profiles, and strategic analysis. Contact now for your free research sample and subscribe to our newsletters to make your decisions researched and well-versed.

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