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news.The results of a new study show that treatment with an anti-C5 complement blocking antibody significantly reduced bronchial inflammation and airway constriction, suggesting its potential as a treatment for asthma.
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The study was conducted in animal models by researchers at Alexion Pharmaceuticals, the Yale University School of Medicine and the Brigham and Women’s Hospital. Alexion believes the results may help position eculizumab, its lead chronic anti-C5 complement blocking antibody drug currently in late stage clinical trials, as a clinical candidate for treatment in severe asthma.
The study demonstrated that both C5a and C5b-9 contribute to the initiation of airway inflammation and in immediate and sustained airway hyperreactivity. Importantly, the researchers found that animals given an anti-C5 blocking antibody – either systemically or when inhaled through a nebulizer – showed substantial reductions in airway reactivity even in the face of ‘airway challenges’ with methacholine, a drug administered to confirm an asthma diagnosis.
The findings also demonstrate that C5 blockade provides more comprehensive and significant reductions in both airway hyperreactivity and pulmonary inflammation than does blockade of a related target, C5a, alone. The anti-C5 blocking antibody, unlike other existing asthma therapies, blocked a wide range of inflammatory mediators known to contribute to the severity and persistence of asthma, including white blood cells and inflammatory mediators from eosinophils and neutrophils. This data suggests a direct role for complement-mediated inflammation in the pathogenesis of severe asthma.
“These findings, together with human clinical data showing complement activation in asthmatic patients, strongly suggest that complement activation is likely to be very important in the development of inflammation in allergic asthma,” said Dr William Busse, the Charles E Reed professor of medicine and the head of allergy and clinical immunology at the University of Wisconsin-Madison Medical School. “Since this is a new area of exploration in asthma, anti-C5 therapy may have the advantage of providing a novel class of therapeutics for the treatment of this severe disease.”