Washington Editor

Partners Chiron Corp. and Nektar Therapeutics Inc. began pivotal testing of their investigational antibiotic known as TIP, a tobramycin inhalation powder.

The Phase III program includes two trials to evaluate its efficacy and safety in treating lung infections caused by Pseudomonas aeruginosa in patients living with cystic fibrosis (CF). The first study, called ASPIRE I, recently got under way.

"TIP's advantage will be, we believe, its convenience and ease of use for patients," said Richard Tate, Chiron's associate director of corporate communications. "With cystic fibrosis patients, compliance is often an issue, particularly because a lot of them are younger. So the necessary time to sit and self-administer treatment can be challenging."

Phase I data have suggested that TIP can significantly reduce the treatment burden for CF patients because of its short administration time and portability, and following dialogue with the FDA on such findings, Emeryville, Calif.-based Chiron decided to move into pivotal development. TIP is administered by way of an inhaler developed in collaboration with Nektar, a drug delivery company that also played a role in reformulating tobramycin by way of its pulmonary dry powder technology. It provides a convenient, easy-to-use solution that, Tate said, "we hope will drive compliance among patients and therefore improve their overall health." John Patton, a co-founder of Nektar and its chief scientific officer, noted that the technology allows for treatments such as TIP to "target local lung infections."

To further test that premise, the multinational ASPIRE I trial will randomize subjects to either the drug or placebo during the first 28 days, after which all patients will enter two treatment cycles with the active drug. The double-blinded, multicenter study's primary endpoint is a measure of its efficacy relative to placebo.

Similarly, ASPIRE II also is a randomized, multicenter, multinational trial, though it will follow an open-label design to assess TIP's safety compared to Chiron's already marketed product in this space, TOBI (tobramycin inhalation solution). It is expected to begin next year.

While a visible difference between TIP and TOBI are their respective powder and solution formulations of tobramycin, Tate told BioWorld Today that "the real difference is the ease of use and the shorter administration time that the device and powder formulation provides for."

Both ASPIRE I and II, which will enroll a total of 500 patients, are scheduled to conclude in 2007 with a potential launch in 2008. The studies are designed for FDA approval as well as overseas registrations.

Should TIP receive marketing clearances, Tate noted that Chiron does not expect it to cannibalize TOBI's existing market share. That product, which the FDA approved in 1997, generated $213 million in sales last year.

"We don't necessarily think that it will replace TOBI, but we certainly think that it will be a well-received alternative" Tate added. Instead, he said Chiron views TIP "as an expansion of the franchise, a line extension or product enhancement, if you will."

Chiron is running the Phase III program, though specific terms of its relationship with San Carlos, Calif.-based Nektar have not been disclosed. Jennifer Ruddock, Nektar's associate director of communications, said that its deals generally provide for milestone payments, production reimbursement and eventual royalties on sales of products borne of its collaborative reformulation efforts and accompanying device developments. She added that Nektar's top-line royalty and manufacturing revenue on sales from its pulmonary partnerships typically range between 10 percent and 20 percent.

Nektar, which has a number of other collaborative relationships based on its delivery technologies, including programs related to inhaled insulin, pegylated Factor VIII and pegylated tumor necrosis factor, is beginning to build an internal pipeline employing those same technologies as well. Its initial work is focused on a powder formulation of an antifungal for bone marrow transplants and an inhaled liquid formulation of an antibiotic for ventilated patients in intensive care units.

On Wednesday, Chiron's stock (NASDAQ:CHIR) lost 22 cents to close at $43.31, while shares in Nektar (NASDAQ:NKTR) fell 60 cents to $16.36.