Positive results from Transave's Phase II ARIKACE clinical trials

Transave Inc., today reported additional positive clinical trial results on its lead investigational drug, ARIKACE(TM) (liposomal amikacin for inhalation), an antibiotic that aims to treat chronic lung infections. The latest results along with previously reported data demonstrate significant clinical benefits and complete the company's Phase II program in two indications - for the treatment of lung infections due to the bacterium, Pseudomonas aeruginosa in cystic fibrosis (CF) patients and non-CF bronchiectasis patients.

The new data from the Phase II clinical trial program in CF patients with Pseudomonas lung infections indicate that ARIKACE, delivered at a dose of 560 mg once daily for 28 consecutive days, demonstrated superior clinical benefit compared to placebo as measured by a significant and sustained improvement in lung function, improvement in patient reported outcomes and reduction in Pseudomonas density. In addition, ARIKACE was well-tolerated with overall adverse events comparable to placebo. The Phase II program results were presented Oct. 17 at the 23rd annual North American Cystic Fibrosis Conference in Minneapolis, Minn., by JP Clancy, M.D., of the Children's Hospital of Alabama and the University of Alabama at Birmingham. The Phase II results were from a prospectively designed pooled analysis of two randomized, double-blind and placebo-controlled studies of 105 patients at 33 European and U.S. sites. Preliminary data from a third CF trial which is an on-going open label study where ARIKACE is being dosed in multiple cycles were also presented, showing continued improvement in lung function over repeat cycles.

"We now have consistent positive results from three placebo controlled and three open label studies of ARIKACE in CF and non-CF bronchiectasis patients," said Tim Whitten, Transave's President and Chief Executive Officer. "To date, studies suggest that ARIKACE has the potential to improve upon the standard of care in the treatment of chronic Pseudomonas lung infections, and further studies are merited in an effort to bring this medicine to market."

In the U.S., ARIKACE was administered once daily for 28 days at 70 mg, 140 mg and 560 mg doses using a novel inhalation device, the eFlow® Electronic Nebulizer (PARI Pharma GmbH). This study included member institutions of the Cystic Fibrosis Foundation's Therapeutics Development Network. In Europe, ARIKACE was administered once daily for 28 days at 280 mg and 560 mg dosages, also using the eFlow® Electronic Nebulizer. Improved lung function was dose-related with the higher 560 mg dose resulting in the greatest improvement in lung function which was sustained for 28 days after treatment ended. Adverse events reported were consistent with those expected in a population of CF patients receiving inhaled medicine, and no differences between groups in the overall rates of adverse events.

"Once-a-day ARIKACE, providing sustained improvement even after therapy ends, suggests that it is possible to treat these stubborn Pseudomonas lung infections while reducing the treatment burden that these patients currently endure," said Dr. Clancy. "Further, the potential for ARIKACE to penetrate the biofilm and achieve a sustained improvement in lung function would be an important advance in this field."

Study results have consistently demonstrated significant reduction in Pseudomonas bacterial density in both mucoid and non-mucoid strains of Pseudomonas. Mucoid strains of Pseudomonas are associated with the presence of biofilms. A biofilm is a protective gel-like barrier formed by colonies of the common and often chronic Pseudomonas bacteria. The bacterial cells encased within the biofilm are difficult to kill because many antibiotics either stick to the surface of the biofilm and/or are cleared away before they can act on the bacteria inside the biofilm. ARIKACE was designed with small (0.3 micron), neutral liposomes that enable significant drug penetration into the biofilm, which may be an important advantage for improving treatment of lung infections due to Pseudomonas.

"ARIKACE development shows great promise for CF patients," said Robert J. Beall, Ph.D., President and CEO of the Cystic Fibrosis Foundation. "We have supported its development in hopes that trials would demonstrate the potential of ARIKACE to improve lung function and quality of life for CF patients."