Source: Eur Urol  |  Posted 5 years ago

MARLBOROUGH, M.A. -- May 31, 2006 -- Sepracor Inc. announced that it presented two arformoterol tartrate inhalation solution posters at the International Conference of the American Thoracic Society (ATS) in San Diego.

Arformoterol tartrate inhalation solution is a long-acting beta-agonist formulation for long-term maintenance treatment of chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema.

A New Drug Application (NDA) for arformoterol tartrate inhalation solution is currently under U.S. Food and Drug Administration (FDA) review. The Prescription Drug User Fee Act (PDUFA) date for arformoterol is October 12, 2006. A PDUFA date is the date by which the FDA is expected to review and act on an NDA submission.

Arformoterol, a single isomer of formoterol, is the first long-acting bronchodilator to be developed in an inhalation solution for use with a nebulizer, which is a machine that converts liquid medication into a fine mist that is inhaled through a mask; other long-acting bronchodilators currently available in the U.S. are formulated in dry-powder inhalers.

Nebulized Arformoterol in COPD: A Prospective Phase III Clinical Trial
This multicenter, double-blind, double-dummy, randomized Phase III study of 717 patients evaluated airway function improvement in patients with COPD who were treated with either arformoterol 50 mcg once daily, arformoterol 25 mcg twice daily, arformoterol 15 mcg twice daily, salmeterol metered-dose inhaler (Serevent(R)) 42 mcg twice daily, or placebo.

Both an albuterol metered-dose inhaler (MDI) as rescue therapy and an ipratropium bromide MDI as supplemental medication for COPD were provided to all patients in this study to be used on an as-needed basis.

In this study, patients treated with arformoterol by nebulizer demonstrated significant and sustained improvement in airway function over 12 weeks of treatment versus patients administered placebo.

In this study, patients treated with arformoterol ([]P <.[]001) and salmeterol ([]P <.[]001) demonstrated a clinically meaningful and significant improvement in morning trough FEV1 over 12 weeks, versus patients administered placebo. FEV1 refers to the amount of air forcefully exhaled in one second and is a test of lung function.

Patients in each arformoterol treatment group ([]P <.[]001) demonstrated significantly greater improvement than those patients administered placebo, in the% change from pre-dose in the 12-hour FEV1 area under the curve (AUC) throughout the study. Patients treated with salmeterol ([]P <.[]001) also demonstrated significant improvement versus placebo in% change from pre-dose in 12-hour FEV1 AUC in this study. Percent change in the area under the curve is one important measure of the magnitude of effect in lung function improvement.

The results also demonstrated that the percentage of patients who were treated with arformoterol who achieved a greater than or equal to 10% improvement in FEV1 from pre-dose levels ranged from 93.7% to 95.7% at Week 0 and 77.1% to 87.5% at Week 12 versus patients administered placebo, who achieved 55.2% at Week 0 and 47.6% at Week 12.

The percentage of patients treated with salmeterol who achieved greater than or equal to 10% improvement in FEV1 from pre-dose levels was 85.1% at Week 0 and 58.4% at Week 12. Both arformoterol and salmeterol demonstrated adequate time to onset for maintenance treatment of COPD: at Week 12, the time to achieve a 10% improvement in FEV1 was 4 to 14 minutes for those patients treated with arformoterol and was 132.3 minutes for patients treated with salmeterol. Overall, arformoterol was well tolerated in this study.

"I believe that these results offer evidence of the potential medical benefit of arformoterol," said James Donohue, M.D., Professor of Medicine and Division Chief of Pulmonary Diseases and Critical Care Medicine, University of North Carolina, School of Medicine, Department of Medicine at Chapel Hill. "Many patients with COPD already use nebulizers for their respiratory medications, and they may prefer nebulization to metered-dose or dry-powder inhaler therapy. I expect that these patients would benefit from having the option of a nebulized long-acting bronchodilator for the treatment of their COPD."

A Crossover Dose-Ranging Study of Nebulized Arformoterol in Patients with COPD
Also presented were results of a 62-patient, 5-way crossover study in patients with COPD. This study evaluated bronchodilation produced by arformoterol 9.6 mcg once daily, 24 mcg twice daily, 48 mcg once daily and 96 mcg once daily, and salmeterol 42 mcg twice daily, versus placebo. Both an albuterol MDI as rescue therapy and an ipratropium bromide MDI as supplemental medication for COPD were provided to all patients in this study to be used on an as-needed basis.

Patients treated with arformoterol ([]P <.[]001) showed significant improvement in bronchodilation as measured by change in FEV1 AUC, versus patients administered placebo. Mean% change in FEV1 AUC from pre-dose was 13.8% for the 9.6 mcg dose of arformoterol, 22.4% for the 24 mcg twice daily dose, 23.14% for the 48 mcg dose, and 23.14% for the 96 mcg dose. Arformoterol was well tolerated in this study.

About Arformoterol
Sepracor completed more than 100 preclinical and 16 clinical studies of arformoterol involving more than 2,000 patients. Among the clinical studies conducted were two 12-week pivotal studies, each with more than 700 patients, as well as a large-scale, 12-month safety study. In phase 3 studies, patients treated with arformoterol demonstrated a statistically significant improvement in FEV1 versus those patients administered placebo.

About COPD
According to the National Center for Health Statistics, COPD is the fourth leading cause of death in the U.S., and in 2003, an estimated 11 million adults in the U.S. had COPD. Approximately 24 million adults have evidence of impaired lung function, which may indicate that COPD is under-diagnosed, according to the National Heart, Lung, and Blood Institute (NHLBI).

COPD is a slowly progressive disease of the airways that is characterized by a gradual loss of lung function. According to the NHLBI, COPD includes chronic bronchitis, chronic obstructive bronchitis and emphysema, or combinations of these conditions. Bronchodilator medications are used to improve airflow and COPD symptoms, and to reduce the occurrence and/or severity of exacerbations in patients affected by COPD.

Serevent is a registered trademark of Glaxo Group Limited Corporation.

SOURCE: Sepracor Inc.