Almirall, S.A. (ALM.MC) and Forest Laboratories, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved Tudorza(TM) Pressair(TM) (aclidinium bromide inhalation powder) for the long-term maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema.
COPD is a common, progressive, and debilitating lung disease characterized by persistent airflow limitation that makes it hard to breathe; it is currently the third leading cause of mortality in the US. Characteristic symptoms include breathlessness, excessive production of sputum, and a chronic cough.
Tudorza(TM) is a twice-daily inhaled long-acting anticholinergic, also referred to as a long-acting muscarinic antagonist (LAMA). Tudorza(TM) produces bronchodilation by inhibiting acetylcholine's effect on muscarinic receptors in the airway smooth muscle. Forest expects Tudorza(TM) Pressair(TM) to be available to wholesalers in the fourth calendar quarter of 2012.
"The FDA approval of Tudorza(TM)Pressair(TM)demonstrates our steadfast commitment to the development of respiratory compounds, such as aclidinium, innovative delivery devices, and our unfailing belief in their potential for the treatment of COPD. Today, we celebrate this achievement for our company and, most importantly, for the patients we serve," commented Jorge Gallardo, President of Almirall.
"We are pleased with the FDA approval of Tudorza. As the first long-acting inhaled anticholinergic agent approved in over 8 years for COPD, Tudorza will be an important treatment option available for the millions of patients living with this serious disease. Tudorza's approval marks an important milestone in our ongoing partnership with Almirall and advances Forest's respiratory franchise and our commitment to COPD patients," commented Howard Solomon, Chairman, Chief Executive Officer, and President of Forest Laboratories.
Professor Richard Casaburi, MD, Associate Chief for Research in the Division of Respiratory and Critical Care Physiology and Medicine, Harbor-UCLA Medical Center, stated, "the Global Initiative for Chronic Obstructive Lung Disease 2011 guidelines recommendlong-acting anticholinergics as a first-line therapy for a broad range of COPD patients with moderate to very severe disease. Tudorzawill be a valuable anticholinergic option in the clinical armamentarium available to manage this serious disease."
The Tudorza(TM) Pressair(TM) clinical development program included a dose-ranging trial and 3 confirmatory pivotal trials. The two 12-week and one 24-week pivotal placebo-controlled trials evaluated the efficacy and safety of Tudorza(TM) 400 mcg twice daily in 1,277 patients. Patients enrolled in these trials had a clinical diagnosis of COPD, were 40 years of age or older, had a smoking history of at least 10 pack-years, a post-bronchodilator forced expiratory volume in one second (FEV1) of at least 30% and less than 80% of predicted normal value, and a ratio of FEV1 over forced vital capacity (FEV1/FVC) of less than 0.7.
In all 3 pivotal trials, Tudorza(TM) Pressair(TM) demonstrated statistically significant improvements in bronchodilation, as measured by change from baseline in morning pre-dose trough FEV1 at 12 weeks (the primary endpoint) compared to placebo. The mean 12-week pre-dose FEV1 improvements vs placebo were 0.12 L, 0.07 L, and 0.11 L in the 3 trials, with a 24-week improvement of 0.13 L in the 6-month trial. Mean peak improvements in lung function assessed after the first dose of Tudorza were similar to those observed at week 12 in each study. Tudorza(TM) had a low incidence of side effects in these trials.
The most common adverse reactions that occurred in the Tudorza(TM) Pressair(TM) group with a frequency of greater than or equal to 3% and exceeding placebo were headache (6.6% vs 5.0%), nasopharyngitis (5.5% vs 3.9%), and cough (3.0% vs 2.2%). Three long-term safety studies, evaluating 891 patients treated with Tudorza(TM) Pressair(TM) 400 mcg twice daily for 40 to 52 weeks reported similar adverse events, with no new safety findings compared to the placebo-controlled trials.
Additionally, serial spirometric evaluations of FEV1 were performed over 12 hours in a subset of patients in the three trials. Improvement of lung function with Tudorza(TM) Pressair(TM) versus placebo was achieved for the first 12 hours on day 1 and was consistent over the 3- or 6-month treatment period evaluated.
In two of the three trials, patients treated with Tudorza Pressair also used less daily rescue albuterol compared to placebo treated patients.