AstraZeneca and Amgen's tezepelumab demonstrated statistically significant and clinically meaningful results in the Phase III WAYPOINT trial for patients with chronic rhinosinusitis with nasal polyps (CRSwNP). The trial met both co-primary endpoints, showing a reduction in nasal polyp size and nasal congestion compared to placebo.
The WAYPOINT trial was a randomized, double-blind study evaluating the efficacy and safety of subcutaneous tezepelumab in adults with severe CRSwNP. Participants remained symptomatic despite treatment with standard-of-care intranasal corticosteroids (INCS).
Clinical Impact and Expert Commentary
Dr. Joseph Han, co-primary investigator and Vice Chair of Rhinology & Endoscopic Sinus and Skull Base Surgery, Allergy, Otolaryngology-Head and Neck Surgery, Eastern Virginia Medical School, US, noted the significant impact of CRSwNP on patients' daily lives, citing disturbances in smell, taste, sleep, pain, and fatigue. He emphasized that the WAYPOINT data demonstrate tezepelumab's potential as a new treatment for patients whose lives are disrupted by this debilitating disease.
Dr. Brian Lipworth, co-primary investigator and 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, highlighted the burden on patients, including repeat surgeries and frequent high-dose oral corticosteroids, which have serious systemic side effects. He stated that the tezepelumab data are clinically meaningful and offer hope for a potential new treatment option that may reduce the burden on patients and healthcare systems.
Mechanism of Action and Disease Context
Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, expressed excitement about the positive results, stating that they reinforce tezepelumab’s first-in-class mode of action, targeting TSLP at the top of the inflammatory cascade, effectively addresses the multiple drivers of epithelial-driven inflammatory diseases.
CRSwNP is characterized by persistent inflammation of the nasal mucosa accompanied by nasal polyps, which can block nasal passages and lead to breathing problems, difficulty in sense of smell, nasal discharge, facial pain, and sleep disturbance. Epithelial dysfunction and inflammation are important characteristics of chronic rhinosinusitis. Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine implicated in shared pathophysiological processes underlying severe asthma and CRSwNP.
Current treatments include intranasal and/or systemic corticosteroids, surgery, and biologics.
Trial Design and Endpoints
The WAYPOINT trial was a double-blind, multi-center, randomized, placebo-controlled, parallel-group trial. Participants received tezepelumab or placebo via subcutaneous injection. The trial included a post-treatment follow-up period of 12-24 weeks for participants who completed the 52-week treatment period.
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, measured by the participant-reported Nasal Congestion Score. Key secondary endpoints included loss of smell; improvement in disease-specific health-related quality of life as measured by SinoNasal Outcome Test (SNOT-22) score; Lund-Mackay score; time to surgery decision and/or systemic corticosteroids for nasal polyposis; Nasal Polyposis Symptom Diary total symptom score and, in the population with co-morbid asthma, pre-bronchodilator FEV1 at Week 52.
About Tezepelumab
Tezepelumab is a first-in-class human monoclonal antibody that inhibits the action of TSLP, a key epithelial cytokine critical in the initiation and persistence of allergic, eosinophilic, and other types of airway inflammation. It is currently approved for the treatment of severe asthma in the US, EU, Japan, and nearly 60 countries.
