Redefining approaches to asthma: developing targeted biologic therapies

Asthma is a chronic respiratory disorder canonically associated with type 2 airway inflammation as characterized by elevated levels of eosinophils, immunoglobulin E, and cytokines including interleukin (IL) 4, IL5, IL9, and IL13 and tumor necrosis factor (TNF) α. However, mounting evidence has shown that considerable heterogeneity exists in human asthma in terms of the nature and intensity of airway inflammation. While many asthma patients achieve acceptable control of symptoms with standard-of-care therapies such as β₂-adrenergic agonists and inhaled corticosteroids, a minority remains symptomatic despite maximal standard-of-care therapy and constitutes a significant unmet medical need. A growing number of investigational therapeutics under clinical development for asthma are biologic therapies that specifically target mediators of type 2 airway inflammation. In this chapter, we consider the biological functions of therapeutic targets in asthma and data from clinical trials of biologic agents directed against these targets. We discuss recent clinical trial results in terms of four key components of drug development: target selection, molecule selection, outcome selection, and patient selection, with particular attention paid to the emerging role of biomarkers in clinical development for asthma.