Chiron Corporation announced that the US Food and Drug Administration (FDA) has accepted the company's New Drug Application (NDA) for marketing approval of Pulminiq (cyclosporine, USP) inhalation solution. The NDA also has been granted priority review designation, which sets an agency action letter due date of six months from the time of filing. Chiron announced the NDA submission for Pulminiq on October 14, 2004.
"Because the potential value of this therapy to improve the survival of and prevent chronic rejection in lung-transplant patients is significant, we are very pleased that the FDA has decided to grant Pulminiq a priority review," said Craig Wheeler, president, Chiron BioPharmaceuticals. "Approximately 4,000 patients in the United States are currently awaiting lung transplants, and Pulminiq could significantly benefit those fortunate enough to receive transplants."
Priority review designation is granted to products that would be a significant improvement compared to marketed products in the treatment, diagnosis or prevention of a disease. Chiron is seeking an indication for Puliminiq for the increase in survival and prevention of chronic rejection in patients receiving allogeneic lung transplants, in combination with standard immunosuppressive therapy. Pulminiq would be the first immunosuppressant approved for this indication.
The NDA for Pulminiq is supported by clinical data from subjects exposed to the drug for at least 2 years. A pivotal randomized double-blinded, placebo-controlled trial of cyclosporine inhalation solution (CyIS) conducted at the University of Pittsburgh enrolled patients who underwent single-lung or double-lung transplants and were on standard immunosuppressive therapies.
Data from the pivotal trial demonstrates a 79 per cent decrease in the risk of death for patients receiving Pulminiq compared to patients receiving placebo during the study period. Fourteen (46.7 per cent) of the placebo-treated patients died prior to study closure, as compared to three (11.5 per cent) of the CyIS-treated patients. The estimated survival duration hazard ratio was 0.213, which equates to a 79 per cent decrease in the risk of death for patients receiving CyIS compared to patients receiving placebo during the study period. Overall there were 18 (60 per cent) patients with histologically proven bronchiolitis obliterans or death in the placebo arm versus five (19 per cent) in the CyIS arm (P=0.003), and fewer CyIS-treated subjects died or developed bronchiolitis obliterans syndrome grade 1 or higher (39 per cent of the CyIS-treated subjects versus 70 per cent of the placebo-treated subjects; P=0.020).
However, the rate of grade 2 or higher acute rejections was 7.9 per cent higher in the placebo arm than in the CyIS arm (P=0.73) and did not appear to have an effect on the development or prevention of acute rejection. Side effects included probable treatment-related bronchospasm manifested by exacerbated dyspnea and airway irritation.
Pulminiq contains 300mg/4.8mL cyclosporine, USP for administration by inhalation. Pulminiq delivers cyclosporine directly to the lungs, achieving greater drug concentration at the rejection site than intravenous or oral cyclosporine. Cyclosporine, an immunosuppressant, has previously been approved in other products as a standard treatment for chronic rejection of kidney, liver and heart allogeneic transplants.