Positive Phase III efficacy data reported for revefenacin as a treatment of COPD.- Theravance + Mylan.

Theravance Biopharma, Inc. and Mylan N.V. announced the presentation of additional positive efficacy data from the three-month, pivotal Phase III studies of revefenacin (TD-4208) at the 2017 CHEST annual meeting in Toronto, Ontario. Revefenacin is an investigational long-acting muscarinic antagonist (LAMA) and a proposed once-daily, nebulized bronchodilator in development for the treatment of chronic obstructive pulmonary disease (COPD). James F. Donohue, MD, Professor of Medicine, Pulmonary Diseases and Critical Care Medicine at the University of North Carolina at Chapel Hill, presented new data from the completed three-month Phase III studies, which included more than 1,250 patients with moderate to very severe COPD, in two separate presentations.

24-Hour Serial Spirometry Subgroup : The first presentation highlighted prespecified exploratory efficacy outcomes for the 264-patient subgroup that underwent 24-hour serial spirometry following the last dose of revefenacin on day 84 in the replicate Phase III studies (0126 and 0127). Results demonstrated statistically significant and clinically meaningful improvements for revefenacin over placebo in trough forced expiratory volume in one second (FEV1) at all time points measured in each study over 24 hours post-dose. The improvements in trough FEV1 versus placebo (0-24 h) were 111-185 mL and 154-269 mL for 88 mcg and 175 mcg, respectively (p < 0.01).

St. George's Respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT): An additional presentation on the Phase III studies reported results from a prespecified secondary analysis which measured changes in patient health status using the St. George's Respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT). In the first Phase III trial (Study 0126), researchers reported clinically meaningful improvements in SGRQ for revefenacin as compared to placebo in both the responder and total score analyses. Treatment with both doses of revefenacin led to statistically significant improvements in total CAT scores (p ? 0.001), as well as the percentage of patients who experienced clinically meaningful improvements in total CAT score (p ? 0.05), as compared to placebo. In the second Phase III (Study 0127), improvements in SGRQ in both the responder and total score analyses were similar for both revefenacin doses. However, due to a greater than expected placebo response in this study, only the change from baseline analysis for subjects receiving 175 mcg reached statistical significance over placebo. Treatment with 175 mcg of revefenacin led to statistically significant improvements in total CAT scores (p < 0.05), as well as an increase in the percentage of patients who experienced clinically meaningful improvements in total CAT score (p ? 0.05), as compared to placebo. While the 88 mcg dose of revefenacin also led to improvements in total CAT scores and an increase in the percentage of patients who experienced clinically meaningful improvements in total CAT score as compared to placebo, these results did not reach statistical significance due to the greater than expected placebo response in this study.

Theravance Biopharma and Mylan previously reported positive results from two pivotal Phase III efficacy studies of revefenacin, which demonstrated statistically significant and clinically meaningful improvements for revefenacin as compared to placebo in trough FEV1 and in overall treatment effect on trough FEV1 (OTE FEV1) after 12 weeks of dosing. Both doses of revefenacin had comparable rates of adverse events to placebo, low rates of serious adverse events, and no clinically meaningful differences in blood parameters or electrocardiogram (ECG) data, across all treatment groups (active and placebo). As previously reported, the most commonly reported adverse events, across both trials and across all treatment groups, were exacerbations, cough, dyspnea and headache.