Therapeutic Targeting of Type 2 Inflammation for the Treatment of Severe Asthma
Lawren C. Wu, Joseph R. Arron, Jeffrey M. Harris, John G. Matthews and Karin Rosen
Affiliation: Department of Immunology, Genentech Inc., 1 DNA Way, MS-34, South San Francisco, CA 94080 USA.
Keywords: Asthma, eosinophil, IgE, IL-13, IL-5, IL-9, periostin, Th2.
Patients with severe asthma have disease that is poorly controlled despite use of standard combination therapies
consisting of high doses of inhaled corticosteroids with other controller medications. Given the persisting disease and burden
of morbidity for many of these patients, there remains a significant need for the development of new therapeutics to
treat severe asthma. Preclinical studies have established a model of asthma pathogenesis that is driven by type 2 inflammation.
Based on this paradigm, a number of therapeutic agents that target key features of type 2 inflammation, such as
immunoglobulin E (IgE), mast cells, eosinophils, and type 2 inflammatory cytokines, have been generated and progressed
into clinical development. Coupled with recent insights into the heterogeneity of asthma that have led to the development
of diagnostic biomarkers to help select patients who may experience greater clinical benefit from these agents, several of
these therapeutics have shown promising effects in clinical studies, with one therapeutic currently on the market. Here we
review the results of clinical studies for these therapeutics and discuss how our understanding of asthma pathogenesis and
disease heterogeneity may be leading to a new generation of therapies for severe asthma.
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