Astellas today announced that the U.S. Food and Drug Administration (FDA) has approved its New Drug Application (NDA) for the use of CRESEMBA® (isavuconazonium sulfate), the prodrug for isavuconazole, for patients 18 years of age and older in the treatment of invasive aspergillosis and invasive mucormycosis (also known as zygomycosis). These are life-threatening fungal infections predominantly occurring in immunocompromised patients.
"We're pleased with the FDA's approval of CRESEMBA for use in treating patients with these life-threatening infections," said Bernie Zeiher, M.D., executive vice president, Global Development and therapeutic area head of Infectious Disease at Astellas. "We are proud to be able to offer a new treatment for patients in an area for which there is a significant unmet medical need."
"It is extremely gratifying to have been a part of the clinical trials of CRESEMBA since inception, knowing patients and their physicians will now have this option," said Thomas F. Patterson, M.D., FACP, FIDSA, Division of Infectious Diseases chief at The University of Texas Health Science Center at San Antonio and director of the San Antonio Center for Medical Mycology. "CRESEMBA is an important new therapy for physicians treating patients with invasive aspergillosis and invasive mucormycosis fungal infections."
The safety and efficacy profile of CRESEMBA in patients with invasive aspergillosis and invasive mucormycosis was demonstrated based on data from the CRESEMBA development program. The safety and efficacy profile of CRESEMBA in patients with invasive aspergillosis was demonstrated based on data from two Phase 3 clinical trials in adult patients with invasive fungal infections: SECURE, a randomized, double-blind, active-control study of adult patients with invasive aspergillosis; and VITAL, an open-label non-comparative study of CRESEMBA in adult patients with invasive aspergillosis and renal impairment or in patients with invasive fungal disease caused by other rare fungi.
In the SECURE study (a study of 516 patients), CRESEMBA demonstrated non-inferiority to voriconazole on the primary endpoint of all-cause mortality at day 42 for the treatment of adult patients with invasive aspergillosis or other filamentous fungi. All-cause mortality through Day 42 was 18.6 percent in the CRESEMBA treatment group and 20.2 percent in the voriconazole treatment group.
The safety and efficacy profile of CRESEMBA in patients with invasive mucormycosis was demonstrated based on data from the VITAL study, which included a subpopulation of 37 patients with invasive mucormycosis treated with CRESEMBA. All-cause mortality in CRESEMBA-treated patients was 38 percent. The efficacy of CRESEMBA for the treatment of invasive mucormycosis has not been evaluated in concurrent, controlled clinical trials.
In the SECURE study, the overall safety profile for CRESEMBA demonstrated similar rates of mortality and non-fatal adverse events as the comparator, voriconazole. The most frequent adverse events for patients treated with CRESEMBA in clinical trials were: nausea (26%), vomiting (25%), diarrhea (22%), headache (17%), elevated liver chemistry tests (17%), hypokalemia (14%), constipation (13%), dyspnea (12%), cough (12%), peripheral edema (11%), and back pain (10%).
The recommended loading dose of CRESEMBA is one reconstituted vial or two capsules (372 mg isavuconazonium sulfate equivalent to 200 mg of isavuconazole) every eight hours for six doses (48 hours) via oral or intravenous administration. The recommended maintenance dose is one reconstituted vial or two capsules (372 mg isavuconazonium sulfate equivalent to 200 mg of isavuconazole) once per day via oral or intravenous administration, starting 12 to 24 hours after the last loading dose. Capsules can be taken with or without food. CRESEMBA for injection must be administered through an in-line filter over a minimum of one hour.
The CRESEMBA New Drug Application (NDA) was submitted by Astellas on July 8, 2014. CRESEMBA is being co-developed with Basilea Pharmaceutica International Ltd. Basilea submitted a European Marketing Authorization Application on July 16, 2014 for the treatment of invasive aspergillosis and mucormycosis in adults.
Upon this approval, Astellas will pay a CHF 30 million milestone payment to Basilea Pharmaceutica International Ltd. under their license and co-development agreement.