AstraZeneca and Amgen's Tezspire (tezepelumab) has demonstrated positive results in the Phase III WAYPOINT trial for patients with chronic rhinosinusitis with nasal polyps (CRSwNP). The trial showed a statistically significant and clinically meaningful reduction in nasal polyp size and nasal congestion compared to placebo. These findings offer a potential new treatment option for individuals whose lives are significantly impacted by this condition.
WAYPOINT Trial Details
The WAYPOINT trial was a randomized, double-blind study evaluating the efficacy and safety of subcutaneous tezepelumab compared to placebo in adults with severe CRSwNP. Participants in the trial continued to experience symptoms despite treatment with standard intranasal corticosteroids (INCS).
Clinical Significance
Dr. Joseph Han, Vice Chair of Rhinology & Endoscopic Sinus and Skull Base Surgery, and Allergy, Otolaryngology-Head and Neck Surgery, Eastern Virginia Medical School, a co-primary investigator in the trial, noted the significant impact of nasal polyps on patients' daily lives, including disturbances in smell, taste, sleep, pain, and fatigue. He emphasized that the WAYPOINT trial data demonstrate tezepelumab's potential as a novel treatment for 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, a co-primary investigator in the trial, highlighted the burden experienced by patients with nasal polyps, including repeat surgeries and frequent use of high-dose oral corticosteroids, which can lead to 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
Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, explained that the positive results from the WAYPOINT trial demonstrate the significant benefit of tezepelumab for patients with nasal polyps. She emphasized that these results reinforce tezepelumab's first-in-class mechanism of action, targeting thymic stromal lymphopoietin (TSLP) at the top of the inflammatory cascade, effectively addressing the multiple drivers of epithelial-driven inflammatory diseases.
Safety and Tolerability
The safety profile and tolerability of tezepelumab in the WAYPOINT trial were consistent with the known profile of the medicine.
Current Treatment Landscape and Unmet Needs
CRSwNP is characterized by persistent inflammation of the nasal mucosa accompanied by benign growths, called nasal polyps. These polyps can block nasal passages, leading to breathing problems, difficulty in sense of smell, nasal discharge, facial pain, and sleep disturbance. Current treatments include intranasal and/or systemic corticosteroids, surgery, and biologics. There remains a need for more effective and targeted therapies to reduce the burden of this condition.
Tezepelumab's Role
Tezepelumab is a first-in-class human monoclonal antibody that inhibits the action of TSLP, a key epithelial cytokine involved in the initiation and persistence of allergic, eosinophilic, and other types of airway inflammation. It is already approved for the treatment of severe asthma in multiple countries.
Trial Endpoints
The co-primary endpoints of the WAYPOINT trial 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 (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.
