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IsavuconazoleIsavuconazole (drug substance: isavuconazonium sulfate) is an investigational once-daily intravenous and oral broad-spectrum antifungal for the potential treatment of invasive fungal infections. This kind of infections predominantly occurs in immunocompromised patients such as cancer patients undergoing chemotherapy.

A European Union (EU) Marketing Authorization Application and a U.S. New Drug Application for isavuconazole are currently under regulatory review by the European Medicines Agency (EMA) and the U.S. FDA, respectively, for the treatment of invasive aspergillosis and mucormycosis (also known as zygomycosis) in adults.

Isavuconazole was designated a Qualified Infectious Disease Product (QIDP) by the U.S. Food and Drug Administration (FDA) under the U.S. Generating Antibiotics Incentives Now (GAIN) Act for the treatment of invasive aspergillosis, mucormycosis, and candidiasis. In addition, it has EU and U.S. orphan drug status for invasive aspergillosis and mucormycosis.

Isavuconazole is being co-developed with Astellas Pharma Inc. Basilea holds full rights to isavuconazole in markets outside of the U.S. and Canada where Astellas is the exclusive license holder.

About the isavuconazole phase 3 program
The phase 3 program with isavuconazole includes three studies, SECURE, VITAL and ACTIVE. The SECURE study was a global double-blind randomized study and evaluated the safety and efficacy of once-daily isavuconazole versus twice-daily voriconazole in the primary treatment of invasive fungal disease caused by Aspergillus species or other filamentous fungi. The VITAL study was an open-label study of isavuconazole in the treatment of aspergillosis patients with pre-existing renal impairment or patients with invasive fungal disease caused by emerging and often fatal molds such as Mucorales, yeasts, or dimorphic fungi. The ACTIVE study evaluates the safety and efficacy of intravenously (i.v.) and orally administered isavuconazole versus i.v. caspofungin followed by oral voriconazole in the treatment of candidemia and other invasive infections caused by Candida yeasts.1 Results from the SECURE2 and VITAL3 studies have already been reported, while enrollment into the ACTIVE study is anticipated to be completed by early 2015.

The need for new antifungal therapies
The expansion of the immunocompromised patient population including cancer patients with chemotherapy-induced neutropenia and transplant recipients receiving immunosuppressive therapy has led to an increased incidence of invasive fungal infections.

Invasive aspergillosis is estimated to occur in 5-13% of bone marrow transplant recipients, 5-25% of patients who have received heart or lung transplants, and 10-20% of patients who have received intensive chemotherapy for leukemia.4 Mortality rates for transplant patients with invasive aspergillosis have been reported to be between 34% and 58%.5 Around 47% of solid organ transplant recipients who developed invasive aspergillosis had renal insufficiency and acute renal failure was reported for 43% of intensive care unit (ICU) patients with invasive aspergillosis, compared to 20% in the general ICU population.5, 6

Mucormycosis (also known as zygomycosis) is an often lethal fungal infection caused by certain emerging molds. Mucormycosis is associated with high morbidity and mortality rates in immunocompromised patients such as patients undergoing chemotherapy or bone marrow transplantation.7, 8 Left untreated, mucormycosis is almost always lethal, and even with appropriate medical management, mortality rates remain high.9

There is a high medical need to address the limitations of current therapies, most importantly the gaps in the antifungal spectrum, unwanted side effects, limited dosing flexibility as well as the development of resistance.

1. identifier: NCT00413218
2. J. Maertens et al. A phase 3 randomised, double-blind trial evaluating isavuconazole vs. voriconazole for the primary treatment of invasive fungal disease caused by Aspergillus spp. or other filamentous fungi (SECURE). European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 2014, oral presentation O230a
3. F. M. Marty et al. An open-label phase 3 study of isavuconazole (VITAL): Focus on mucormycosis. IDWeek conference 2014, poster 824
4. E. M. Harman. Medscape Reference, Drugs, Diseases & Procedures, Aspergillosis Clinical Presentation, [Accessed August 20, 2014]
5. J. W. Baddley et al. Factors associated with mortality in transplant patients with invasive aspergillosis. Clinical Infectious Disease 2010 (50), 1559-1567
6. K. H. Vandewoude et al. Invasive aspergillosis in critically ill patients: attributable mortality and excesses in length of ICU stay and ventilator dependence. Journal of Hospital Infection 2004 (56), 269-276
7. F. Lanternier et al. A global analysis of mucormycosis in France: the RetroZygo study (2005-2007). Clinical Infectious Diseases 2012 (54), S35-S43
8. J. Ambrosioni et al. Emerging invasive zygomycosis in a tertiary care center: epidemiology and associated risk factors. International Journal of Infectious Diseases 2010 (14S), e100-e103
9. J. Wingard. Zygomycosis: Epidemiology and treatment options. Proceedings 2006 (6), S526-S530


IDSA Infectious Diseases Society of America