From 1980 to 1996, the number of Americans afflicted with asthma more than doubled to almost 15 million, with children under five years old experiencing the highest rate of increase. The steady rise in the prevalence of asthma constitutes an epidemic, which by all indications is continuing. Even if rates were to stabilize, asthma would continue to be a profound public health problem, each year responsible for 9 million visits to health care providers, over 1.8 million emergency room visits, and over 460,000 hospitalizations. As well as placing a considerable burden in terms of direct medical costs, asthma is one of the leading causes of work or school absenteeism. In 1990, the annual cost of asthma to the US economy was estimated to be $6.2 billion, with the majority of the expense attributed to medical care. The epidemic in the US is representative of many developed countries.

Paralleling the dramatic growth in its incidence, asthma is driving one of the most rapidly growing global therapeutic markets. The impact that increased incidence is having on therapeutic market values is further increased by a considerable degree of under-treatment of asthma. Global revenue for 2001 from asthma therapies has been reported by some to be as high as $11.7 billion and up until recently annual growth rates of 10-15% have been reported. Most sources however predict that this level of growth is not sustainable. Since the anti-asthmatic market is well served by existing therapies, such as the beta2-agonists and corticosteroids which can treat 95% of asthma patients competition within the anti-asthmatic market will grow increasingly intense. Consequently, to attain commercial success, pipeline products need to offer significant advantages over currently marketed therapies.

LeadDiscovery in collaboration with Professor Peter Barnes (head of Thoracic Medicine at the National Heart and Lung Institute, asthma field-leader and panelist for the Global Initiative for Asthma) have recently produced a state of the art evaluation of emerging asthma therapeutics and future drug discovery targets. One target that was fully evaluated in this report is interleukin-5 (IL-5).

IL-5 plays an essential role in orchestrating the eosinophilic inflammation of asthma. IL-5 gene deletion or monoclonal antibodies to IL-5 markedly suppress the eosinophilic response of mice to allergen and the subsequent airway hyperreactivity. The antibody effect may last for up to 3 months after a single intravenous injection of antibody in primates, making treatment of chronic asthma with such a therapy a feasible proposition. Humanized monoclonal antibodies to IL-5 have been developed and a single intravenous infusion of one of these antibodies (mepolizulab) markedly reduces blood eosinophils for several weeks and prevents eosinophil recruitment in to the airways after allergen challenge in patients with mild asthma. However this treatment has no significant effect on the early or late response to allergen challenge or on baseline hyperreactivity, suggesting that eosinophils may not be of critical importance for these responses in humans. More recently a biopsy study has demonstrated that anti-IL-5 antibody, while profoundly reducing eosinophils in the circulation (by over 95%), is less effective at reducing eosinophils in bronchial biopsies (by ~50%), which may explain why this treatment is not clinically effective. Most recently, researchers at Ghent University Hospital have published results from their pilot study evaluating the safety, biological activity and pharmacokinetics of SCH55700, a second humanized anti-human IL-5 antibody, in subjects with severe persistent asthma treated with oral or high doses of inhaled steroids. In a double blind, randomized, multicenter trial, a rising single dose of SCH55700 was administered intravenously and found to dose dependently reduced circulating eosinophil counts. At a dose of 1 mg/kg, the decrease remained significant up to day 30. After administration of 0.3 SCH55700, baseline FEV1 was improved at 24 hours. No significant changes occurred in other clinical indices of disease activity. Adverse events were not different between active treatment and placebo leading the authors to conclude that the therapeutic efficacy of SCH55700 needs to be further addressed.

Entry date Wednesday, April 23, 2003

Adapted from Kips et al, Am J Respir Crit Care Med 2003 Mar 20; [epub ahead of print] - Interested in collaborating with this group? Contact LeadDiscovery or the authors direct.

Interested in collaborating with this group? Contact leaddiscovery@bioportfolio.co.uk