Theravance Reports Results from Phase 2B Study 0091 with TD-4208 for COPD, Says Met Primary Efficacy Endpoint

Theravance,Inc. (NASDAQ: THRX) today announced positive topline results from adose-ranging 7-day cross-over design Phase 2b study of TD-4208, aninvestigational long-acting muscarinic antagonist (LAMA),administered once-a-day as a nebulized aqueous solution in patientswith moderate to severe chronic obstructive pulmonary disease (COPD).The primary efficacy endpoint in this study was change from baselinein trough FEV1 (forced expiratory volume in one second) at the end ofDay 7."We are very pleased with the positive results of the Phase 2b studyof TD-4208 in patients with COPD," said Mathai Mammen, M.D., Ph.D.,Senior Vice President of Research and Early Clinical Development. "Weare encouraged that we have identified doses of TD-4208 that provideclinically meaningful levels of bronchodilation, as well as lowerdoses that do not. Additionally, TD-4208 demonstrated a 24 hourprofile consistent with a once-a-day regimen."TD-4208 met the primary efficacy endpoint for all six doses studied(ranging from 22 mcg to 700 mcg), and demonstrated a statisticallysignificant change versus placebo from baseline in trough FEV1. Thedose of 175 mcg was identified as the lowest that demonstrated aclinically meaningful change in FEV1 versus placebo at trough of 114mL (95% CI: 76,153).Serial FEV1 measurements over 24 hours on Day 7 demonstratedcomparable bronchodilation over the first (0-12 hours) and second(12-24 hours) 12-hour periods. TD-4208 demonstrated a low peak totrough ratio for TD-4208 consistent with a once-a-day dosing regimen.TD-4208 pharmacokinetics demonstrated low (sub-pharmacologic) andpredictable systemic exposure following dosing.All doses of TD-4208 were generally well tolerated in the study withrates of adverse events comparable to placebo. The most commonadverse events were headache, cough, and dyspnoea. Review oflaboratory panels revealed no abnormal trends. There were noplacebo-adjusted increases in heart rate or any ECG parameter at anyof the doses at any time point. In addition, there were nodiscontinuations from the study attributed to adverse events relatedto study drug. Three patients experienced serious adverse events: oneon placebo and two on TD-4208 22 mcg, none of which were consideredto be treatment related.