Asthma is a chronic inflammatory disorder of the airways in which patients may experience acute exacerbations. Disease severity varies according to a patient’s genetic pre-disposition to certain risk factors, as well as their response to environmental allergens and particulate matter in chemical pollutants. The allergens associated with triggering the inflammation associated with the disease include tree and grass pollens, pollutants, and respiratory viral infections. Asthma ultimately results from a dysregulated immune system and allergens or certain chemicals found in pollutants initiate an over-production of immunoglobulin E (IgE), which then triggers the release of various chemical mediators from mast cells in the upper and lower airways. Chronic or repeated release of these mediators creates persistent inflammation that can lead to reversible airway obstruction and airway hyperresponsiveness, and the symptoms of asthma — wheezing, shortness of breath, excess mucus production and cough. As inflammation persists, a process known as “remodeling” occurs whereby the tissue of the lungs become less elastic. This ultrastructural alteration gradually reduces the efficiency of oxygen exchange and airflow, increasing the frequency, duration and severity of asthma attacks. In addition, exercise and cold air are other known initiating factors that trigger bronchial smooth muscle hyperreactivity and asthmatic symptoms.
In 2007, the prevalence of asthma in the United States, Japan, United Kingdom, France, Italy, Germany and Spain (7 main countries) was estimated at just under 60 million. While asthma prevalence appears to have stabilized in these main markets, asthma also accounts for over 150,000 deaths per year. In the US and the EU, the financial burden of asthma is estimated at over $16 billion each. In 2007, the asthma market across the 7 main countries totaled approximately $20 billion, and is predicted to grow to $25 billion by 2017. The most significant growth driver over the last few years has been the long-acting ß2-agonists/inhaled corticosteroid combination products, which constituted 35% of sales, followed by the anti-leukotrienes, and inhaled corticosteroids making up some 15% and 14%, respectively, of the market share. Despite high diagnosis rates (88% across the 7 main countries) and effective management of episodic attacks, there is still a high unmet medical need for disease modifying therapies. Such therapies would demonstrate the efficacy of combination products in relieving and controlling asthma symptoms, however, there is a great need to improve on the safety profiles and introduce products that can reduce the inflammation and prevent the irreversible airways remodeling, at the same time promoting high compliance amongst the patient population. Additionally, new therapies are needed for a growing number of patients that are not well controlled by corticosteroid or β-2 agonist therapies.