National Editor

Less than a year after entering a potential $545 million deal with GlaxoSmithKline plc to find new, long-acting beta2-agonists for respiratory diseases, Theravance Inc. said a pair of early Phase II studies yielded positive results.

"We get milestone payments throughout the development life cycle for the initiation of trials," said David Brinkley, the privately held company's senior vice president for commercial development.

In the finished studies, the compound GSK 159797 - known as TD-3327 from South San Francisco-based Theravance's research - achieved the target increase in forced expiratory volume at 1 second (the FEV1 measure) throughout the 25-hour evaluation period in a study of 38 patients with mild asthma following single-dose inhalation. It was well tolerated, with no increase in heart rate, the company reported.

Another treatment, GSK 597901, also proved encouraging, although fewer details were disclosed. The next step is Phase IIb trials to help determine the dosage that will be used in Phase III.

"We're really interested in focusing on [GSK 159797]," Brinkley told BioWorld Today, but the drug candidates "are pooled for joint development, so we receive the same royalty regardless of whose compound makes it to market."

Glaxo said it is working toward a next-generation, once-daily combination consisting of its GSK 685698, a new long-acting corticosteroid, and GSK 159797. The former has shown evidence of greater potency and the potential for once-daily dosing, compared to existing treatments; Glaxo expects a regulatory filing for the drugs in combination in 2008.

London-based GlaxoSmithKline and Theravance signed their deal at the beginning of the year to develop selective, once-daily, long-acting beta2-agonists (LABAs) for asthma and chronic obstructive pulmonary disease (COPD). (See BioWorld Today, Jan. 7, 2003.)

Under the terms, up to eight LABA compounds from Glaxo and Theravance will be put into a pool for potential development, with Glaxo responsible for developing and commercializing them. When the alliance began, two of the pooled compounds already were in Phase I studies, but Theravance would not disclose from which company each originated.

The industry has been trying to develop single-dose LABAs for 20 to 30 years, Brinkley said, and the inhaler will use Glaxo's proprietary delivery technology, already on the market in Advair Diskus, approved by the FDA in November for COPD associated with chronic bronchitis - the first time that a product containing both an anti- inflammatory (fluticasone) and a long-acting bronchodilator (salmeterol) has been approved for the condition.

"My daughter's asthmatic, and she uses it," Brinkley said. "Compared to the other devices, it's fantastic."