AstraZeneca and Amgen's Tezspire (tezepelumab) has met both co-primary endpoints in the Phase III WAYPOINT trial, demonstrating a statistically significant and clinically meaningful reduction in nasal polyp size and nasal congestion compared to placebo in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). The trial results offer hope for a new treatment option for individuals affected by this debilitating condition.
WAYPOINT Trial Details
The WAYPOINT trial is a randomized, double-blind, multi-center, placebo-controlled study that evaluated the efficacy and safety of subcutaneous Tezspire in adult patients with severe CRSwNP. Participants in the trial remained symptomatic despite treatment with standard of care, including intranasal corticosteroids (INCS). 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.
Clinical Significance
"Chronic rhinosinusitis with nasal polyps negatively impact patients’ daily lives with 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 the burden of current treatments: "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."
Mechanism of Action
Tezepelumab is a first-in-class human monoclonal antibody that inhibits thymic stromal lymphopoietin (TSLP), a key epithelial cytokine at the top of multiple inflammatory cascades. TSLP is critical in the initiation and persistence of allergic, eosinophilic, and other types of endothelial inflammation associated with severe asthma and other inflammatory diseases. By blocking TSLP, tezepelumab may prevent the release of pro-inflammatory cytokines by immune cells, potentially preventing exacerbations and improving disease control.
Current Approvals and Future Development
Tezspire is currently approved for the treatment of severe asthma in the US, EU, Japan, and nearly 60 countries. Beyond CRSwNP, tezepelumab is also in development for other potential indications, including COPD and eosinophilic esophagitis (EoE).
