Releasing a bit of good news, Chiron Corp. submitted a new drug application for Pulminiq inhalation solution for lung transplant patients.

Specifically, the Emeryville, Calif.-based company is seeking a label for the increase in survival and prevention of chronic rejection in patients receiving allogeneic lung transplants, in combination with standard immunosuppressive therapy. Pulminiq (cyclosporine, USP) could be the first immunosuppressant approved for that indication.

"There haven't been substantial improvements in treatment for lung transplant patients in the last 10 years or so," Richard Tate, a spokesman at Chiron, told BioWorld Today. "So while therapies for other types of transplants, such as kidneys, hearts, etc., have improved, lung transplant patient treatment has not improved. Pulminiq would be a breakthrough treatment for patients, as there currently aren't any therapies indicated for chronic rejection."

The product contains 300 mg/4.8 mL cyclosporine for administration by inhalation. It delivers cyclosporine directly to the lungs, achieving greater concentration at the rejection site than intravenous or oral cyclosporine, an immunosuppressant that has been approved in other products as a standard treatment for chronic rejection of kidney, liver and heart allogeneic transplants.

Chiron last year acquired exclusive worldwide commercial rights to the product from Novartis Pharma AG, of Basel, Switzerland. Financial terms of the arrangement were not disclosed, and at the time, the product was referred to as aerosolized cyclosporine. (See BioWorld Today, April 23, 2003.)

The FDA named it an orphan drug a year ago, and Chiron has applied for priority review. The company plans to market Pulminiq on its own.

"This is a product that leverages our existing pulmonary sales force with TOBI, and cystic fibrosis patients are often lung transplant recipients," Tate said. "This is certainly something that fits with our portfolio, in terms of our presence with pulmonary physicians, and that sales force is in place."

TOBI is an inhalable tobramycin solution for cystic fibrosis patients chronically infected with Pseudomonas aeruginosa; it generated $51 million in sales for the quarterly period ended June 30.

The FDA application is based in part on data from a pivotal trial of cyclosporine inhalation solution (CyIS) that showed that 14 of the placebo-treated patients died prior to study closure (46.7 percent), compared to three of the CyIS-treated patients (11.5 percent). The study enrolled patients who underwent single lung or double lung transplants and who were on standard immunosuppressive therapies. The estimated survival duration hazard ratio was 0.213, which equates to a 79 percent decrease in the risk of death for patients receiving CyIS, compared to patients receiving placebo.

Overall there were 18 patients (60 percent) with histologically proven bronchiolitis obliterans or death in the placebo arm vs. five (19 percent) in the CyIS arm (p=0.003), and fewer CyIS-treated subjects died or developed bronchiolitis obliterans syndrome Grade 1 or higher (39 percent vs. 70 percent of the placebo-treated subjects; p=0.020). However, the rate of Grade 2 or higher acute rejections was 7.9 percent 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.

"This is some positive news for us," Tate said. "It illustrates that we're certainly moving toward the goals and objectives that we laid out for 2004."

The NDA is supported by more than 12 years of data from clinical studies in lung transplant patients conducted at the University of Pittsburgh. Findings from the randomized, double-blinded, placebo-controlled trial are being reported at this week's North American Cystic Fibrosis Conference in St. Louis.

In other news released at the conference, Chiron and Nektar Therapeutics, of San Carlos, Calif., reported Phase I data showing that tobramycin powder for inhalation might reduce the treatment burden for cystic fibrosis patients by offering a short administration time and full portability. The inhaled antibiotic is being developed for the treatment of cystic fibrosis patients with infections caused by Pseudomonas aeruginosa.

In a development related to Chiron's announcement last week that it would not supply flu vaccines to the U.S. market, a stockpile expected to make up about half the country's total supply, the company was named in a federal class-action lawsuit with claims of securities fraud. The suit was filed in the U.S. District Court for the Northern District of California on behalf of stockholders who bought into the company between July 23, 2003, to Oct. 5, 2004. (See BioWorld Today, Oct. 6, 2004.)

The complaint noted the one-day stock value drop of 16.3 percent when Chiron disclosed that UK regulatory authorities would not permit it to ship the expected 46 million to 48 million doses of Fluvirin this year. Questions about the flu vaccine first surfaced late this summer, when Chiron divulged sterility issues with a small number of Fluvirin lots manufactured at the UK site in question. (See BioWorld Today, Aug. 30, 2004.)

The class-action suit follows news of investigations by the SEC and the U.S. Attorney's Office for the Southern District of New York, though Tate declined to comment.

Separate filings with the SEC confirm government queries into Chiron. The company disclosed that it received a grand jury subpoena by the U.S. Attorney's Office requesting certain documents and materials relating to the flu vaccine and the suspension of its license to manufacture it at a facility in Liverpool, UK. Also, a notice from the SEC indicated that it has opened an informal inquiry to determine whether Chiron violated certain provisions of the federal securities laws.

The company noted in its filing that it "intends to fully cooperate with" both the U.S. Attorney's Office and the SEC in their inquiries.

On Thursday, Chiron's stock (NASDAQ:CHIR) rose 9 cents to close at $31.96. Its 52-week high is $57.29.

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