IL-5 is a target for severe asthma because it regulates eosinophil maturation and survival. Eosinophils normally defend the body against helminthic parasites and other pathogens, but in some people with severe asthma, these white blood cells accumulate in the lungs and promote airway inflammation after bronchial provocation by allergens. IL-5 inhibitors such as Bosatria and Cinquil stop the cytokine docking to the alpha chain of the IL-5 receptor complex on the surface of eosinophils and their precursor cells; benralizumab, by comparison, binds the receptor's alpha chain directly.
Not all severe asthma is driven by eosinophilic inflammation, but in those individuals where it is, IL-5 inhibition can be beneficial. In two phase 3 trials of Bosatria, the results of which were published September 25 in The New England Journal of Medicine, IL-5 blockers reduced airway hyper-responsiveness and improved various clinical endpoints. In one of the studies, led by researchers at GSK's Respiratory Therapeutic Area Unit in Research Triangle Park, North Carolina, 385 patients with severe eosinophilic asthma received intravenous or subcutaneous Bosatria, every four weeks. After 32 weeks, the treatment halved the exacerbation rates compared with the 191 patients in the placebo arm (0.93 and 0.81 exacerbations per patient per year in the intravenously and subcutaneously treated groups, compared with 1.75 in the placebo arm; N. Engl. J. Med. 371, 1198–1207, 2014). “It's an incredibly large change to an incredibly meaningful endpoint,” says coauthor Steven Yancey, GSK's medicine development leader for Bosatria.
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