Arcapta (indacaterol) is the first long-acting beta-2 agonist (LABA) approved for once-daily use. FDA approved indacaterol in July 2011 for maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD).^1,2 The medication received approval in Europe in 2009 at doses of 150 and 300mcg and has demonstrated safety and efficacy in six clinical trials that included 5,474 patients ages 40 and older with a clinical diagnosis of COPD.^2,3 Indacaterol is not approved for the treatment of asthma and maintains the same black box warning that LABAs increase the risk of asthma-related death.² The approved U.S. treatment dose of indacaterol is 75mcg (contents of one capsule) inhaled once daily at the same time every day with the Neohaler device with the most common adverse effects reported during indacaterol use including runny nose, cough, sore throat, headache and nausea.¹

COPD is the fourth leading cause of death in the United States according to the Centers for Disease Control and Prevention.⁴ While smoking cessation remains a primary goal in the management of COPD, current guidelines recommend regular treatment with long-acting inhaled bronchodilators for patients with moderate and severe symptoms, with the addition of inhaled corticosteroids (ICS) for those patients with severe disease and repeated exacerbations.⁵ Currently available long-acting inhaled bronchodilators are the long-acting anticholinergic (LAAC) tiotropium and the LABAs, salmeterol and formoterol.

Indacaterol offers another treatment option for the management of COPD, but it is of note, that only two of the six confirmatory trials that lead to its approval utilized the approved dose of 75mcg daily. The remaining trials included doses similar to those approved for use in Europe including 150, 300, and 600mcg once daily. All six trials enrolled patients with a clinical diagnosis of COPD, who were 40 years or older, had a smoking history of at least 10 pack years, had a post-bronchodilator FEV₁ less than 80% and at least 30% of the predicted normal value and a post-bronchodilator ratio of FEV₁ over FVC of less than 70%.¹ The primary efficacy endpoint was 24-hour post dose trough FEV₁ after 12 weeks of treatment in all six trials with other endpoints including rescue medication use, symptoms, and health-related quality of life.¹ In all trials, indacaterol demonstrated significantly greater 24-hour post-dose trough FEV₁ compared to placebo at 12 weeks.¹

Place in Therapy

Indacaterol offers an alternative treatment option for patients with moderate to severe symptoms associated with COPD, such as wheezing and breathlessness. The once-daily dosing of indacaterol is the most obvious advantage to its use over other currently available LABAs, but this has been an advantage of the once-daily dosed LAAC tiotropium. A trial conducted to assess the efficacy of indacaterol vs. tiotropium demonstrated that indacaterol dosed at either 150 or 300mcg daily was found to be at least as effective as tiotropium 18mcg daily in its effect on symptoms and health status⁶ Currently, the main limitation to routine use of indacaterol would be the approved dose of 75mcg daily as this is below the approved dose in Europe and the majority of clinical trials assessing indacaterol efficacy. The approved dose was based in part on a blinded meta-analysis comparing indacaterol-treated patients to controls with respect to composite incidence of COPD-related deaths, hospitalizations, and intubations.⁷

Indacaterol should be available in early 2012 and based on current evidence may be a good alternative for patients taking a twice-daily dosed LABA and struggling with compliance. While indacaterol offers an alternative option to tiotropium, its efficacy at the approved 75mcg dose is lacking and requires further assessment for routine use as a first-line option.

References:

1. Arcapta (indacaterol) Professional Product Label. At: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022383s000lbl.pdf Accessed November 21, 2011.

2. U.S. Food and Drug Administration. Arcapta (indacaterol): FDA approves Arcapta Neohaler to treat chronic obstructive pulmonary disease [Internet]. [updated 2011 July 1; cited 2011 Nov 1]. Available from http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm261649.htm

3. European Medicines Agency. European Public Assessment Report (EPAR) for Onbrez Breezhaler (indacaterol). Available at: http://www.ema.europa.eu/docs/en _GB/document_library/EPAR_-_Summary_for_the_public/human/001114/WC500053733.pdf. Accessed 21 November, 2011

4. Centers for Disease Control and Prevention. Fast Stats: Death and Mortality [Internet]. [updated 2011 Oct 24; cited 2011 Nov 21]. Available from http://www.cdc.gov/nchs/fastats/deaths.htm

5. Global initiative for chronic obstructive lung disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of chronic obstructive pulmonary disease (accessed November, 2011). Available from www.goldcopd.com

6. Donohue JF, Fogarty C, Lotvall J, et al. Once-daily bronchodilators for chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2010;182:155-162.

7. Hudd TR, Zaiken K. Management of chronic obstructive pulmonary disease: An emphasis on recently approved medications and products in the pipeline. Formulary 2011;46:374-393.