The ultra–long-acting beta-agonist (LABA) indacaterol holds promise for the treatment of chronic obstructive pulmonary disease (COPD), said Mario Cazzola, MD, Professor of Respiratory Medicine, University of Rome Tor Vergata, Italy. In preclinical and early clinical studies, indacaterol demonstrated a fast onset of action and 24-hour bronchodilation.
Indacaterol has already been approved in the European Union, but the US Food and Drug Administration has requested additional data before again considering it for the treatment of COPD.
The high intrinsic activity of indacaterol may allow for faster activation of beta-receptor, permitting fast onset of action. In a study of 89 patients with COPD, single doses of indacaterol (150 μg and 300 μg) had an onset of action that was similar to that of salbutamol and faster than that of salmeterol-fluticasone (Balint B, et al. Int J Chron Obstruct Pulmon Dis. 2010; 5:311-318).
Indacaterol’s interaction with lipid rafts may explain its 24-hour bronchodilation, Dr Cazzola said. In one study (Lombardi D, et al. Eur J Pharm Sci. 2009;38:533-547), indacaterol had equivalent interaction with lipids to salmeterol but had a 2-fold higher affinity for raft microdomains.
In the INERGIZE COPD phase 3 clinical trials released by Novartis in 2009, indacaterol proved superior to current comparators (ie, tiotropium, formoterol, salmeterol) in improvements over placebo in trough forced expiratory volume in 1 second at 12 weeks of treatment, Dr Cazzola said. Its effect on quality of life and breathlessness was also superior to these same comparators. Indacaterol also increased the percentage of days without rescue medication more than these other agents.
In a 1-year comparison of oncedaily indacaterol with twice-daily formoterol and placebo (Dahl R, et al. Thorax. 2010;65:473-479), indacaterol improved the BODE (body mass index, obstruction, dyspnea, exercise) index at week 12 and week 52 compared with placebo. The BODE index correlates with the risk of exacerbations.
In this same study, indacaterol increased the time to first exacerbation over 52 weeks compared with placebo. Indacaterol has a favorable cardiovascular safety profile, with minimal changes in the corrected QT interval observed over 52 weeks, he said.
Cough is a frequent adverse event with indacaterol; 17% to 20% of patients in this study experienced a sporadic, short-lasting cough within 15 seconds after inhalation of indacaterol. In other clinical trials, only 6.8% of patients reported cough as an adverse event, and no patients discontinued the study because of cough, Dr Cazzola noted