The incidence of asthma has dramatically increased over recent years and although currently available treatments are generally effective patient compliance that is currently very poor, especially with respect to inhaled treatment. Furthermore 5% of patients are unresponsive to these treatments and it is this cohort that accounts for a large segment of asthma related healthcare cost. 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. Competition within the anti-asthmatic market will therefore grow increasingly intense. Greater patient compliance or greater efficacy in treatment resistant patients will characterize future successful products.

One treatment profiled in our recent state of the art of asthma therapeutics and drug discovery (click here for access), is Suplatast tosilate (IPD-1151T), a dimethylsulphonium compound. This molecule, which was launched in Japan (1995) by Taiho, inhibits the release of cytokines (IL-4, IL-5) from Th2 cells without effects on IFN-gamma from Th1 cells in vitro. In clinical studies this drug has some clinical benefit in symptomatic asthmatic patients and reduces markers of inflammation and airway hyperresponsiveness. In a recent study designed to further investigate the efficacy and the mechanism of action of Suplatast tosilate, Sano et al sought to determine the suppressive effects of suplatast tosilate on eosinophilic inflammation of the bronchial mucosa in patients with mild asthma. This study reported an improvement in respiratory tract parameters and symptom score. Moreover, the number of infiltrating and activated eosinophils significantly decreased.

This study is of interest not only because provides further evidence supporting the use of suplatast tosilate but also because it suggests that reduced eosinophil infiltration and activation could contribute to its mechanism of action. In previous studies treating patients with moderate to severe asthma with anti-IL-5 dramatically reduced circulating eosinophils, but no significant improvement in either asthma symptoms or lung function was reported. These surprising results question the critical role of eosinophils in asthma and indicate that other strategies aimed at inhibiting eosinophilic inflammation might not be effective. 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. Likewise, blocking IL-4 has also been disappointing with respect to efficacy in patients with mild disease. Although the mechanism of action of Suplatast tosilate remains unclear the significance of its ability to block both IL-4 and IL-5 release and its capacity to reduce eosinophil infiltration and activation in the human airway deserves further study. This could lead to the development of effective strategies for the treatment of asthma.

Adapted from Sano et al, J Allergy Clin Immunol 2003 May;111(5):958-66

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