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Positive Phase III Data Reported for Antifungal Agent Isavuconazole

Superiority over voriconazole demonstrated in patients with invasive aspergillosis

Positive efficacy and safety data from a phase III trial of isavuconazole (Basilea Pharmaceutica/Astellas Pharma) in patients with invasive aspergillosis have been presented at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) in Barcelona, Spain.

In the randomized, double-blind SECURE trial, treatment-emergent adverse events (AEs) were reduced with isavuconazole compared with voriconazole (Vfend, Pfizer) in the system organ classes of hepatobiliary (8.9% vs. 16.2%, respectively), skin (33.5% vs. 42.5%), and eye disorders (15.2% vs. 26.6%). In addition, isavuconazole showed fewer drug-related AEs compared with voriconazole (42.4% vs. 59.8%, respectively). In both treatment groups, the most common treatment-emergent AEs for isavuconazole and voriconazole, respectively, were nausea (27.6% vs. 30.1%), vomiting (24.9% vs. 28.2 %), pyrexia (22.2% vs. 30.1%), and diarrhea (23.7% vs. 23.2%).

Previously announced data showed that the SECURE study met its primary objective of demonstrating the non-inferiority of once-daily isavuconazole versus twice-daily voriconazole for the primary treatment of invasive fungal disease caused by Aspergillus species or certain other filamentous fungi. Baseline characteristics of the severely ill patient population enrolled in this trial were balanced between treatment groups and reflected patients at risk for invasive fungal disease (mean age, 51 years; 84% hematologic malignancies; 66% neutropenic; and 20% allogeneic hematopoietic stem-cell transplantation).

The primary endpoint of all-cause mortality through day 42 in the intent-to-treat population (ITT, N = 516) was 18.6% in the isavuconazole group and 20.2% in the voriconazole group. All-cause mortality through day 42 in patients with proven or probable invasive fungal disease (modified ITT population) was 19.6% for isavuconazole and 23.3% for voriconazole.

Overall response (a composite of clinical, mycologic, and radiologic responses) at the end of therapy in the modified ITT population was 35.0% for isavuconazole versus 36.4% for voriconazole.

Isavuconazole is an investigational once-daily intravenous (IV) and oral broad-spectrum antifungal agent for the potential treatment of severe invasive and life-threatening fungal infections.

Isavuconazole demonstrated in vitro and in vivo coverage of a broad range of yeasts (such as Candida species) and molds (such as Aspergillus species) as well as activity in in vitro studies and in animal models against emerging and often fatal molds, including those that cause mucormycosis. In the U.S., isavuconazole was granted FDA fast-track status and received an “orphan drug” designation for invasive aspergillosis and mucormycosis (zygomycosis).

The phase III clinical program for isavuconazole includes three studies: SECURE, VITAL, and ACTIVE.

The SECURE trial is a global double-blind, randomized study designed to evaluate the safety and efficacy of once-daily isavuconazole compared with twice-daily voriconazole in the primary treatment of invasive fungal disease caused by Aspergillus species or other filamentous fungi.

The VITAL trial is 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, yeasts or dimorphic fungi.

The ACTIVE trial is evaluating the safety and efficacy of IV and oral isavuconazole compared with IV caspofungin (Cancidas, Merck) followed by oral voriconazole in the treatment of invasive Candida infections. Data from the SECURE and VITAL trials were reported in September 2013 and February 2014, respectively.

Invasive aspergillosis is estimated to occur in 5% to 13% of recipients of bone marrow transplants, in 5% to 25% of patients who have received heart or lung transplants, and in 10% to 20% of patients who are receiving intensive chemotherapy for leukemia. Mortality rates for transplant patients with invasive aspergillosis have been reported to be between 34% and 58%. Approximately 47% of solid-organ transplant recipients who developed invasive aspergillosis had renal insufficiency. Moreover, acute renal failure was reported for 43% of intensive-care patients with invasive aspergillosis compared with 21% of the general intensive-care population.

Source: Basilea Pharmaceutica Ltd.; May 14, 2014.

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