A monoclonal antibody with a new mechanism of action has an official go-ahead from regulators in the United States and the European Union for treating chronic rhinosinusitis with nasal polyps. Amgen and AstraZeneca’s Tezspire (tezepelumab) is a human monoclonal antibody that binds thymic stromal lymphopoietin (TSLP), a cytokine expressed in skin, gut, lungs and thymus that functions as an ‘alarmin’ because it is released in response to allergens, viruses, bacteria and air pollution. TSLP signals via a TSLP receptor and drives TH2-mediated inflammation. By preventing TSLP from interacting with its receptor on immune and epithelial cells, Tezspire blocks an apex driver of the inflammatory signaling cascades that cause epithelial inflammation and dysfunction in chronic nasal congestion. This mechanism may mean that Tezspire works better than approved biologics for the condition that target individual cytokines. Sanofi and Regeneron’s Dupixent (dupilumab) blocks interleukin (IL)-4 and IL-13 signaling, while GlaxoSmithKline’s Nucala (mepolizumab) binds IL-5. Another chronic rhinosinusitis treatment, Genentech and Novartis’s Xolair (omalizumab), blocks immunoglobulin E activity.
Results from the phase 3 Waypoint trial published in the New England Journal of Medicine suggest, albeit on the basis of cross-trial comparisons, that the TSLP blocker reduces disease in more patients than these approved biologics. Monthly treatment with Tezspire reduced nasal congestion, glucocorticoid use and polyp size, and almost eliminated the need for surgery (reduced 98%, compared with placebo). Patients’ sense of smell also improved.
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