Disease background

Asthma is a chronic inflammatory disorder of the airways that varies in degree of severity 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. Pollens and certain chemicals found in pollutants can trigger the 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 known contributing factors in triggering the hyperreactivity associated with bronchial smooth muscle, hence asthmatic symptoms.

Medical Need

In 2003, the prevalence of asthma in the United States, United Kingdom, France, Italy, Germany and Spain (6 main countries) was estimated at 42.1 million or just over 7% of the population, with a rise to 8% of the population projected in the next 10 years. Additionally, in the US and the EU, the financial burden of asthma is estimated at over $16 billion each. In 2003, the asthma market across the 6 main countries totaled $11.8 billion, the most significant growth driver coming from the long-acting ß2-agonists/inhaled corticosteroid combination products. The inhaled corticosteroid monotherapies remain strong sales-drivers with the short-acting ß2-agonists/inhaled corticosteroid combination products and leukotriene antagonists (LTA) coming in third and forth, respectively. Despite high diagnosis rates (75% across the 6 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.