Eculizumab for treatment of asthma

Asthma is an inflammatory disease, which can be exacerbated by stimuli such as viral infections and exposure to allergens. Asthma continues to be a profound public health problem due to asthma exacerbation in a low proportion of patients in need of more effective medications.

The C5 complement pathway has been proposed as a new target for the treatment of asthma, supported by clinical observations of increased C5a levels in asthmatic airways, constitutive expression of C5 receptors on bronchial epithelium and smooth muscle cells, and preclinical studies in mice demonstrating inhibition of C5 cleavage reduced established airway inflammation and improves lung function. Eculizumab is a monoclonal antibody, which binds to the complement protein C5, thereby preventing the formation of C5a and C5b-9. The research discussed in this review describes development of eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria and the efficacy of eculizumab on allergen-induced asthmatic responses in a placebo-controlled study.

In an allergen-challenge model of asthma, there was a significant period effect with eculizumab, with inhibition of the late asthmatic response in subjects who received placebo treatment first. Although this study provides some evidence that eculizumab may be effective to attenuate allergen-induced responses, the role of C5 in asthma remains to be clarified.