Tezepelumab

Asthma is a heterogeneous chronic obstructive respiratory disease with both "type 2" (T2) and T2-low endotypes characterized by reduced airflow, chronic inflammation, and airway remodelling. Thymic stromal lymphopoietin (TSLP), an innate pleiotropic IL-2-family cytokine, has emerged as a key upstream regulator of chronic inflammation across asthma endotypes. Blocking the interaction of TSLP with the receptors TSLPR and IL-7Rα improves asthma-associated biomarkers including eosinophil counts and IgE, FeNO, IL-5, and IL-13 levels. As existing asthma treatments such as omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab act on specific downstream mediators of the inflammatory response, they are mostly limited to treating T2 asthma. Conversely, tezepelumab, which targets the upstream master regulator TSLP, has the potential to be effective across asthma endotypes.

Tezepelumab is a human monoclonal IgG2λ antibody directed against TSLP produced in Chinese hamster ovary (CHO) cells by recombinant DNA technology. It was granted FDA approval on December 17, 2021, and is currently marketed under the trademark TEZSPIRE by Amgen/AstraZeneca. Tezepelumab was also approved by the European Commission on September 19, 2022.

Tezepelumab is indicated as an add-on maintenance treatment for patients aged 12 years and older with severe asthma. In Europe, it is reserved for patients who are inadequately controlled despite maintenance treatment with high-dose inhaled corticosteroids plus another drug.

Tezepelumab is not indicated for the relief of acute bronchospasm or status asthmaticus.