Antifungal Agent Isavuconazole Submitted for FDA Review
Treatment targets aspergillosis and mucormycosis
The FDA has received a new drug application seeking approval for isavuconazole (Astellas Pharma/Basilea Pharmaceutica International) for the treatment of invasive aspergillosis and invasive mucormycosis (also known as zygomycosis) — life-threatening fungal infections that predominantly occur in immunocompromised patients.
In February 2014, the FDA designated isavuconazole as a qualified infectious disease product (QIDP) for invasive mucormycosis. A QIDP designation for the treatment of invasive aspergillosis was granted in 2013. The QIDP status provides priority review and a 5-year extension of market exclusivity in the U.S. In addition, in 2013, isavuconazole was granted “orphan drug” status for the treatment of invasive aspergillosis and invasive mucormycosis.
Isavuconazole — the active moiety of the prodrug isavuconazonium sulfate — is an investigational once-daily intravenous and oral broad-spectrum antifungal agent being developed for the 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 against emerging and often fatal molds, including those that cause mucormycosis.
In September 2013, isavuconazole was shown to be non-inferior to voriconazole (Vfend, Pfizer) in a phase III, randomized, double-blind study of patients with invasive fungal disease caused by Aspergillus species or certain other filamentous fungi. Isavuconazole was as effective as voriconazole, as determined by the primary endpoint of all-cause mortality through day 42 in the intent-to-treat population (N = 516). The all-cause mortality rate was 18.6% in the isavuconazole group and 20.2% in the voriconazole group. The 95% confidence interval of the treatment difference between isavuconazole and voriconazole was within the pre-specified non-inferiority margin of 10%.
In addition, the key secondary endpoint of the overall success rate (a composite of clinical, mycologic, and radiologic responses) at the end of therapy in patients with proven or probable disease was similar between isavuconazole and voriconazole (35.0% and 36.4%, respectively).
Overall, drug- and non–drug-related adverse events were reported in 96.1% and 98.5% of patients in the isavuconazole and voriconazole groups, respectively. The most common adverse events were nausea, vomiting, pyrexia, diarrhea, and hypokalemia, which were reported at similar rates in both treatment groups. Drug-related adverse events occurred in 42.4% and 59.8% of patients in the isavuconazole and voriconazole groups, respectively.