ROCKVILLE, Maryland—The US Food and Drug Administration (FDA) has approved Schering-Plough Corporation's Noxafil (posaconazole) Oral Suspension for the prevention of invasive Aspergillus and Candida infections in patients age 13 years and older at high risk of developing these infections. High-risk patients include hematopoietic stem cell transplant recipients with graft-versus-host disease (GVHD) or those with hematologic malignancies with prolonged neutropenia from chemotherapy.
Noxafil, a novel triazole antifungal agent discovered and developed at Schering-Plough Research Institute, is the first and only antifungal agent approved by FDA for prevention of invasive fungal infections (IFIs) caused by Aspergillus species, the company said.
Invasive fungal infections are the leading cause of death among hematopoietic stem cell transplant recipients. In the United States, each year more than 1.3 million hospital patients are affected by IFIs. Currently, if these populations develop such an infection, the mortality rate varies between 60% and 90%.
"Noxafil can help prevent patients from developing life-threatening invasive fungal infections while being treated for serious conditions such as acute leukemia or GVHD," said John Perfect, MD, professor of medicine, Division of Infectious Diseases, Duke University, and director, Duke University Mycology Research Unit. "With this FDA approval, Noxafil offers physicians an important new therapeutic option for preventing invasive fungal infections in patients at high risk," he said.Clinical Trials
The safety and efficacy of Noxafil were evaluated in clinical trials consisting of 1,844 patients between 13 and 82 years of age, according to the FDA. In two randomized controlled studies of patients who had compromised immunity and were at high risk for invasive fungal infections, those patients who received Noxafil had comparable or lower rates of invasive Aspergillus and Candida infections than those patients who received other antifungal medications.Open-Label Study
An open-label study compared Noxafil oral suspension 200 mg three times daily (n = 304) to pooled standard azole therapies (fluconazole oral suspension 400 mg once daily or itraconazole(Drug information on itraconazole) oral solution 200 mg twice daily) (n = 298), as prophylaxis against IFIs in neutropenic patients who were receiving cytotoxic chemotherapy for acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). The study assessed all patients while on therapy plus 7 days and at 100 days postrandomization. Efficacy of prophylaxis was evaluated using a composite endpoint of proven/probable IFIs, death, or treatment with systemic antifungal therapy. Patients may have met more than one of these criteria.
In this study, Noxafil reduced treatment failure (as defined by breakthrough IFIs, death, and use of systemic antifungal therapy), compared with the comparator group (27% vs 42%); reduced proven and probable IFIs vs fluconazole(Drug information on fluconazole)/itraconazole (2% vs 8%); reduced breakthrough Aspergillus infections vs fluconazole/itraconazole (1% vs 7%) (aspergillosis was the most common breakthrough infection seen in the study); decreased all-cause mortality at 100 days postrandomization (14% vs 21%); and had safety and tolerability comparable to that of fluconazole.Double-Blind Study
