Chiron has submitted a New Drug Application (NDA) for marketing approval of Pulminiq, potentially the first therapy indicated specifically for patients living with lung-transplants. The advisory committee was not asked to vote on whether to recommend approval of the drug.

Though expert advice from an advisory committee often is requested as part an NDA review, the final decision regarding approval will be made by the FDA and is expected by July 14.

79 Percent Decrease in Risk of Death

Pulminiq is an inhaled formulation of cyclosporine, an FDA-approved drug that has been part of the standard of care for heart, kidney and liver transplant patients for more than 20 years. In the NDA for Pulminiq, Chiron is seeking an indication to increase survival and prevent chronic rejection in patients receiving allogeneic lung transplants, in combination with standard immunosuppressive therapy.

Clinical data submitted with the NDA demonstrated a 79 percent decrease in the risk of death (P = .007) and a 72 percent decrease in the risk of chronic rejection or death (P = .001) for patients receiving Pulminiq compared to patients receiving placebo. If approved, Pulminiq would be the first drug indicated specifically for the treatment of lung-transplant patients.

"We were grateful for the input we received from the advisory committee," said Stephen Dilly, M.D., chief medical officer, Chiron BioPharmaceuticals. "We look forward to working with the FDA to make this valuable treatment available for patients, and we reiterate our commitment to a large, post-approval study to further document the survival benefit and safety profile of Pulminiq."

Pivotal Study

A single-center, randomized, double-blind trial of Pulminiq was conducted at the University of Pittsburgh Medical Center (UPMC), one of the largest lung-transplant centers in the United States. The trial had two phases: an initial open-label pilot phase and a subsequent randomized blinded phase.

In the pilot phase, 10 patients received open-label Pulminiq and were followed to monitor safety and tolerability.

In the randomized phase, 56 patients were treated following their single- or double-lung transplant with either Pulminiq or placebo. Of these 56 patients, 26 received Pulminiq and 30 received placebo.

All patients underwent an initial dose-titration period to find the maximum tolerated dose up to a protocol-specified maximum of 300 mg or the equivalent volume of placebo. After this 10-day period, patients were to continue therapy three times per week for a period of two years.

The study began in 1997 and concluded in 2003, when the 56th patient completed the full two years of treatment. Follow-up in the randomized cohort ranged from 24 to 56 months. A total of 47 percent of the placebo-treated patients died during the study, compared with only 12 percent of Pulminiq-treated patients.

Lung-Transplant Survival

Approximately 1,100 lung transplants are performed each year in the United States. Despite aggressive care, only 45 percent of lung transplant recipients will be alive five years following the transplant procedure.

By contrast, 70 percent to 90 percent of heart, kidney and liver transplant recipients will be alive at five years. If approved, Pulminiq would represent an important advance in outcomes for lung transplant patients, Chiron said.

Chiron acquired exclusive worldwide commercial development and marketing rights for Pulminiq from Novartis in April 2003. The company was granted orphan drug designation for Pulminiq in November 2003 and submitted an NDA for the product in October 2004.

The NDA later was granted priority review designation, establishing a six-month FDA review period. In January 2005, Chiron announced that the FDA had requested additional analysis of the pivotal study. As a result, the review period was extended. A decision on approval of the Pulminiq NDA is expected by July 14, 2005.