Amgen and AstraZeneca have announced positive top-line results from the Phase 3 WAYPOINT trial, evaluating Tezspire (tezepelumab-ekko) in adult patients with chronic rhinosinusitis with nasal polyps (CRSwNP). The trial met both co-primary endpoints, demonstrating statistically significant and clinically meaningful reductions in nasal polyp size and nasal congestion compared to placebo.
WAYPOINT Trial Details
The WAYPOINT trial was a randomized, double-blind, placebo-controlled study involving adult participants with severe CRSwNP who remained symptomatic despite treatment with standard-of-care intranasal corticosteroids (INCS). Participants received subcutaneous injections of Tezspire or placebo. The co-primary endpoints were the change from baseline in total nasal polyp size, measured by the endoscopic total Nasal Polyp Score, and the change from baseline in bi-weekly mean nasal congestion, assessed via the participant-reported Nasal Congestion Score.
Key secondary endpoints included assessments of loss of smell, disease-specific health-related quality of life (SNOT-22 score), Lund-Mackay score, time to surgery decision and/or systemic corticosteroids for nasal polyposis, and pre-bronchodilator FEV1 in patients with comorbid asthma and aspirin-exacerbated respiratory disease/NSAID-exacerbated respiratory disease (NSAID-ERD) at Week 52.
Clinical Significance
"Chronic rhinosinusitis with nasal polyps negatively impact patients’ daily lives with the obstructions leading to disturbances in smell, taste and sleep, as well as pain and fatigue," said Dr. Joseph Han, vice chair of Rhinology & Endoscopic Sinus and Skull Base Surgery, and Allergy, Otolaryngology-Head and Neck Surgery, Eastern Virginia Medical School, US, and co-primary investigator in the trial. "The impressive data from the WAYPOINT trial demonstrate tezepelumab’s potential as a new treatment for patients whose lives are disrupted by this debilitating disease."
Dr. Brian Lipworth, Professor of Allergy and Pulmonology, Scottish Centre for Respiratory Research, and Tayside Rhinology Ear, Nose and Throat Clinic, Ninewells Hospital University of Dundee in Scotland, UK, and co-primary investigator in the trial, noted, "Patients diagnosed with nasal polyps continue to experience significant burden including repeat surgeries and frequent treatment with high doses of oral corticosteroids, which are associated with serious systemic side effects. The tezepelumab data are clinically meaningful and offer patients with nasal polyps hope for a potential new treatment option that may reduce the burden on patients and healthcare systems."
About Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)
CRSwNP is characterized by persistent inflammation of the nasal mucosa accompanied by soft tissue growths called nasal polyps. These polyps can obstruct nasal passages, leading to breathing problems, impaired sense of smell, nasal discharge, facial pain, and sleep disturbances. Epithelial dysfunction and inflammation are key features of CRSwNP, impairing the epithelium's barrier function against external environmental factors. A significant proportion of CRSwNP patients also have comorbid asthma.
Current treatments include intranasal and systemic corticosteroids, surgery, and biologic medications.
About Tezspire (tezepelumab-ekko)
Tezspire is a first-in-class human monoclonal antibody that targets thymic stromal lymphopoietin (TSLP), a key epithelial cytokine involved in multiple inflammatory cascades. By blocking TSLP, Tezspire can prevent the release of pro-inflammatory cytokines, potentially preventing exacerbations and improving disease control. Tezspire is currently approved for the treatment of severe asthma in multiple countries.
Beyond CRSwNP, Tezspire is also being investigated for other potential indications, including chronic obstructive pulmonary disease (COPD) and eosinophilic esophagitis (EoE).
