Staff Writer

Theravance and partner GlaxoSmithKline plc have started the first in a series of Phase III studies of their next-generation combination treatment for chronic obstructive pulmonary disorder (COPD).

The large-scale Phase III studies will enroll more than 6,000 patients overall and evaluate Theravance's investigational long-acting beta agonist known as 444 and an inhaled corticosteroid, fluticasone.

South San Francisco-based Theravance and London-based GSK have been working together since 2002 to develop the fixed-dose product for COPD. Seven other long-acting beta agonists and three inhaled corticosteroids were reviewed before settling on the current combination in development for COPD.

The many years of development and the positive Phase IIb testing in some 3,000 patients "gives us a lot of optimism about the outcome of the Phase III trials," Theravance CEO Rick Winningham told BioWorld Today.

The main goal of the studies is to measure the rate of COPD exacerbations. Dosing has begun in the first of two 12-month exacerbation studies, and patient screening is under way in three other studies.

In addition to the 12-month studies, the three other trials will be two six-month efficacy and safety studies, a detailed lung function profile study and superiority testing comparing the fixed combination 444 plus fluticasone vs. other COPD treatments. Those three studies will begin enrolling patients in the near future, Winningham said.

All study patients in the program will be dosed using a unique dual strip delivery device developed by GSK.

GSK's Advair, a first-generation long-acting inhaler for COPD, is delivered through the same device that would be used in the next-generation combination product being developed with Theravance.

Currently, Advair sales are about $8 billion a year while Boehringer Ingelheim GmbH's and Pfizer Inc.'s COPD drug Spiriva have topped $3 billion annually.

Twice-a-day Advair could take a back seat to the once-daily new-generation product. As Winningham put it, the hope is to develop a medicine that works "better than Advair."

In addition to COPD, GSK and Theravance also plan to study use of the treatment in asthma patients and expect to release further details about that program in the coming months.

Among their competitors is Basel, Switzerland-based Novartis AG, which also has begun Phase III studies if its pipeline drug (NVA237) for COPD, though part of that program has not begun Phase III. Novartis anticipates having data on the Phase III trials within 18 months after the studies begin and aims to file new drug applications for NVA237 and a 24-hour bronchodilator for COPD (QVA149) in 2011. (See BioWorld Today, June 30, 2009.)

Although the COPD space has generated considerable dealmaking, there also have been some notable setbacks. In August, New York-based Forest Laboratories Inc. and Swiss drugmaker Glenmark Pharmaceuticals SA reported a disappointing Phase II study of oglemilast. But Forest was able to pick up another COPD drug, paying $100 million up front for U.S. rights to Nycomed A/S's Daxas (roflumilast), under review for COPD. (See BioWorld Today, Aug. 11, 2009.)

And earlier this year, Topigen Pharmaceuticals Inc. dropped its COPD candidate TPI 1020 after disappointing Phase II data, followed by another Phase II miss with asthma drug TPI ASM8. (See BioWorld Today, Jan. 12, 2009.)

"We're in a very good competitive position," Winningham said, adding that the differentiating factor with the Theravance-GSK program is that it was previously well studied in 3,000 patients in Phase II, and showed "excellent activity."

The company also is in a good cash position, he said. Theravance finished the second quarter with about $176 million in cash on its balance sheet and was set to release third-quarter results Tuesday afternoon.

Theravance recently earned a milestone payment of $20 million for the approval of Vibativ (telavancin) in September and for supplying collaboration partner, Astellas Pharma US Inc., of Deerfield, Ill., with the launch inventory for the first commercial sale in the U.S. (See BioWorld Today, Sept. 15, 2009.)

Darrell Baker, senior vice president of GSK respiratory medicines development center, said in a statement, "This is an ambitious program that reflects both our confidence in the molecules selected and advances in our understanding of COPD."

Theravance has three other programs that have reached proof of concept in the respiratory area, one of which is partnered with GSK.

Shares in Theravance (NASDAQ:THRX) lost 2 cents Tuesday, closing at $14.75.