Novel And Emerging Therapies
Despite use of current treatments, lung function continues to decline in long-term COPD. Therefore, new classes of drugs and/or non-pharmacological therapies to reduce disease progression are needed (Barnes 2010a; Matera 2012a). Several novel drug therapies are being developed that may offer benefit to people with COPD.
Indacaterol (Arcapta Neohaler®), an ultra-long-acting beta2-agonist, was FDA approved in July 2011 (FDA 2012). It is a bronchodilator with rapid-onset action that remains effective for 24 hours or longer. In clinical trials, a once-daily treatment of indacaterol significantly improved shortness of breath and lung function, exercise endurance, and lung hyperinflation compared to placebo among COPD patients. Also, fewer subjects receiving indacaterol experienced COPD worsening compared to placebo (McKeage 2012; Steiropoulos 2012; Roig 2009).
Glycopyrronium bromide, a novel anticholinergic with rapid-onset action that lasts for 24 hours, is being investigated as a new COPD treatment (EMA 2012). In a clinical trial among COPD patients, significant improvement in forced expiratory volume (FEV1) occurred 5 minutes after dosing and continued to be evident through week 26 of treatment (D'Urzo 2011).
Phosphodiesterase-4 (PDE-4) inhibitors can be used to reduce airway inflammation and exacerbations in severe to very severe COPD with a history of exacerbation and chronic bronchitis. A majority of clinical trials used roflumilast (Daxas®) and cilomilast (Ariflo®), second-generation oral PDE-4 inhibitors. Roflumilast, in particular, is approved in the United States, Canada, and European Union (Diamant 2011). Adverse side effects of PDE-4 inhibitors are nausea, diarrhea, weight loss, sleep problems, and headache (Diamanti 2011).
A safety concern with the anti-inflammatory agents under development is their ability to affect innate immunity, potentially increasing the risk of lung infection and perhaps cancer among people predisposed to COPD (Barnes 2008).
Statins, which treat cardiovascular disease by lowering cholesterol and combatting inflammation, may have potential as a therapy for COPD exacerbations (Matera 2012b; Bartziokas 2011). Statins possess a variety of biological functions including modulation of the inflammatory response, as well as tissue remodeling pathways, both of which are of potential benefit in treating COPD. Analysis of a large randomized trial on statins and cardiovascular disease found that treatment with pravastatin (Pravachol®) reduced exacerbations and death due to COPD (Heart Protection Study 2005). Another randomized trial found that pravastatin use for 6 months improved exercise performance in COPD (Lee 2008). A prospective trial reported that statin treatment in the first year after hospitalization for COPD exacerbation reduced risk and severity of exacerbations and improved quality of life (Bartziokas 2011).