Assistant Managing Editor

Despite hailing two six-month pivotal studies' successes for Relovair in chronic obstructive pulmonary disease (COPD), South San Francisco-based Theravance Inc. saw its shares dinged by nearly a dollar Thursday as investors focused on the one endpoint that fell short of statistical significance.

The company's stock (NASDAQ:THRX) lost 87 cents to close at $23.51.

Detailed data are expected later, but Theravance and partner GlaxoSmithKline plc said top-line results from the two studies supported Relovair's overall development program in COPD. A once-daily inhaled combination treatment comprising long-acting beta agonist (LABA) vilanterol and inhaled corticosteroid (ICS) fluticasone furoate, Relovair is positioned to replace GSK's twice-daily COPD and asthma drug Advair (fluticasone/salmeterol), which pulled in sales of nearly $7 billion in 2009.

Theravance's CEO, Rick Winningham, said he was "encouraged by the data overall," and reminded investors on the company's conference call that the two six-month studies represented "only a portion" of Relovair's 6,000-plus patient Phase III program.

A positive lung function study, plus two ongoing 12-month exacerbation studies will round out the pivotal trials. Data from the 12-month studies are expected later this year.

"We're comfortable with where we are," he said. "We don't see the need to do any additional studies."

The two six-month trials enrolled a total of 2,200 patients with moderate to severe COPD, and each trial randomized patients into one of six treatment arms: fluticasone alone, vilanterol alone, a combination of the two Relovair components at three different fluticasone doses and placebo. Improvements in lung function – forced expiratory volume in one second (FEV1) – over the first four hours post-dose on day 168 and the end of dose trough lung function on day 169 were measured.

Relovair hit statistical significance against placebo. Vilanterol vs. placebo, and an analysis looking at the contribution of vilanterol to the overall performance of Relovair also met the lung function endpoints. But the fourth measure, designed to test the contribution of fluticasone to the overall performance of Relovair, missed showing statistical significance, though all doses demonstrated numerical improvements.

Winningham said the miss could have been due to the sample sizes in the six-month trials, which were "a little low to evaluate the contribution of fluticasone specifically." The six-month studies included about 200 patients in each treatment arm. The 12-month studies have about 400 patients per arm, better powered to show statistical significance.

Assuming positive data from the 12-month trials, Theravance anticipates the six-month trial data to be sufficient. "We expect this will be fine" as a component of regulatory submissions, Winningham added.

The 12-month studies are designed to measure the rate of exacerbations and changes in FEV1 as the primary endpoints.

Relovair, like its predecessor Advair, is designed to treat COPD by incorporating a LABA drug that primarily improves lung function with a corticosteroid that primarily reduces the number of exacerbations. Theravance and GSK also are testing the product in Phase III asthma trials.

The companies have been working together in the respiratory disease space since 2002. In addition to Relovair (formerly known as the Horizon program), the two have moved into Phase III testing with another COPD candidate: a combination once-daily long-acting muscarinic antagonist/LABA drug and vilanterol.

That product will be studied in four large trials designed to compare improvements in lung function between the combination product, its components, placebo and Spiriva (tiotropium, Pfizer Inc.). (See BioWorld Today, Feb. 4, 2011.)

As part of the collaboration, London-based GSK holds a nearly 20 percent stake in Theravance. The big pharma also holds options on several other programs in Theravance's pipeline.

Its COPD programs have taken attention away from Theravance's struggling antibiotic product, Vibativ (telavancin), which gained hard-won approval in 2009 in complicated skin and skin structure infections, but has failed to clear the FDA for the much larger hospital-acquired pneumonia market. (See BioWorld Today, Feb. 1, 2010.)

The company got some good news last month when the European Committee for Medicinal Products for Human Use gave Vibativ a thumbs-up, but most analysts are modeling only modest sales of the drug overseas. Vibativ is partnered with Tokyo-based Astellas Pharma Inc.

Relovair remains the primary value driver. Should the final two Phase III trials come back positive, the drug could launch as early as 2013 and quickly reach blockbuster status.

In the meantime, Theravance remains well capitalized. The company, which reported a net loss of $27.7 million, or 28 cents per share, for the first quarter, had about $293.8 million in cash, equivalents and marketable securities as of March 31 .