Theravance, Inc. (NASDAQ: THRX) announced the results of two studies in an ongoing Phase 2b clinical program to assess the efficacy and safety of the investigational bronchodilators GSK642444 (’444) and GSK159797 (’797), the lead long-acting Beta2 agonist (LABA) compounds in the Beyond Advair collaboration with GlaxoSmithKline (GSK).
In the studies, ’444, a GSK-discovered compound, and ’797, a Theravance-discovered compound, each given once daily, achieved clinically significant increases in bronchodilation at least equivalent to salmeterol given twice daily.
Both compounds exhibited a pharmacodynamic profile similar to other inhaled LABAs, with little impact on heart rate.
All doses studied of compound ’444 (25, 100 and 400 mcg), dosed once a day, showed greater bronchodilator activity than salmeterol dosed twice a day, and produced placebo-adjusted, dose-dependent mean changes from baseline FEV1 (forced expiry volume in one second) of over 200 mL at trough on the fourteenth day of treatment. The two lower doses also produced smaller changes than salmeterol in placebo-adjusted weighted mean heart rate over the first four hours after dosing on day fourteen.
All doses studied of compound ’797 (10, 15 and 20 mcg), dosed once a day, showed comparable bronchodilator activity to salmeterol, dosed twice a day, at trough on the fourteenth day of treatment. The lowest dose also produced a placebo-adjusted, weighted, mean heart rate change over the first four hours after dosing on day fourteen that was similar to that for salmeterol.
“The collaboration is very excited by these results, which showed that both compounds, dosed once daily, demonstrated bronchodilation similar to or better than salmeterol dosed twice daily, and are pleased that both ’444 and ’797 will continue in development,” said Rick E Winningham, CEO of Theravance. “We are especially encouraged by the enhanced bronchodilator effect and potentially greater therapeutic index of ’444, which will progress as the lead compound into 28-day studies in combination with inhaled corticosteroids. We will also continue to explore an optimized dose range for ’797 as a backup.”
The goal of the Beyond Advair collaboration between Theravance and GSK is to develop a once-a-day inhaled combination medicine comprised of a LABA and a corticosteroid for the treatment of asthma and chronic obstructive pulmonary disease.