Phase III Data Showed Novartis Investigational Bronchodilator QAB149 Significantly Improved Lung Function In COPD Patients

Main Category: COPD
Also Included In: Respiratory / Asthma;  Clinical Trials / Drug Trials;  Medical Devices / Diagnostics
Article Date: 27 May 2009 - 4:00 PDT

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The Novartis investigational bronchodilator QAB149 (indacaterol) met the primary efficacy endpoints of improved lung function compared to placebo at 12 weeks in three pivotal phase III studies in chronic obstructive pulmonary disease (COPD) patients. In secondary endpoints of these studies, QAB149 demonstrated clinically relevant lung function improvements within five minutes of the first dose, lasting for 24 hours in COPD patients.

The QAB149 data, which were presented at the American Thoracic Society (ATS) 2009 International Conference in San Diego, are the first from the Phase III INVOLVE, INHANCE and INLIGHT-1 trials. These were three multinational, multi-center, randomized, double-blind, placebo-controlled studies in over 3,800 patients with moderate-to-severe COPD.

"Current management of COPD focuses on the use of bronchodilators to optimize lung function," said Professor Stephen I. Rennard, Pulmonary and Critical Care Medicine, University of Nebraska Medical Center. "As presented at the ATS meeting, QAB149 is a long-acting beta-agonist bronchodilator given once daily that significantly improved both airflow and clinical outcomes. The ability to provide bronchodilation on a once-daily basis will be an important addition to the current therapeutic armamentarium in COPD."

In the six-month INHANCE trial, QAB149 150µg and 300µg doses significantly improved lung function at 12 weeks compared to placebo. Improvements [measured by difference in trough forced expiratory volume in one second (FEV1 )] were observed after one day (110mL and 140mL), at the 12 week primary endpoint (both doses 180mL), and at 26 weeks (160mL and 180mL). Results were statistically significant (p<0.001) for each of the doses compared to placebo at each of these time points.

In the one-year INVOLVE trial, which compared QAB149 (300µg and 600µg doses) and formoterol (12µg dose) with placebo, QAB149 improved symptom control (cough, wheezing, breathlessness, sputum production and color), nights free of awakening and days able to perform usual activities over placebo (secondary endpoints). Both doses of QAB149 demonstrated improvements over twice-daily formoterol in trough FEV1 difference versus placebo after one day (140mL and 170mL vs. 110mL; p<0.05), at 12 weeks (170mL and 170mL vs. 70mL; p<0.001) and at one year (160mL and 150mL vs. 50mL; p<0.001) in exploratory endpoints. Both QAB149 doses and formoterol prolonged the time to first COPD flare-up (exacerbation) compared to placebo [hazard ratios of 0.77 (p=0.030), 0.69 (p=0.003) and 0.77 (p=0.034), respectively].

COPD is a progressive, life-threatening respiratory disease that affects 210 million people worldwide. Commonly caused by cigarette smoke and other harmful fumes, COPD is characterized by a persistent obstruction of airflow from the lungs. While COPD is incurable, improved airflow with the use of long-acting bronchodilators is central to symptom management. According to the World Health Organization, unless urgent action is taken to reduce the risk factors, COPD is projected to become the third leading cause of death worldwide by 2030.

"Novartis is committed to developing a range of therapies for patients with respiratory diseases such as COPD," said John Orloff, M.D., Senior Vice President, US Medical and Drug Regulatory Affairs, Novartis Pharmaceuticals Corporation. "QAB149 could become the foundation for a portfolio of medicines currently in development designed to address unmet needs in respiratory care."

QAB149 given once daily is being investigated for the treatment of COPD. It is not being developed as a single-agent treatment for asthma. QAB149 belongs to a class of medications known as long-acting beta2-agonists or LABAs. In patients with asthma, LABAs may increase the chance of asthma-related death.

In clinical studies, the most commonly reported adverse reactions with QAB149 were nasopharyngitis, upper respiratory tract infection, cough, and headache.

QAB149 is currently undergoing regulatory review in the European Union and the United States.

Soure
Novartis Pharmaceuticals Corporation