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 affected by this debilitating condition.
The WAYPOINT trial was a randomized, double-blind study involving adult participants with severe CRSwNP who remained symptomatic despite treatment with standard intranasal corticosteroids (INCS). The study evaluated the efficacy and safety of subcutaneous administration of tezepelumab compared to placebo over a 52-week treatment period, followed by a 12-24 week post-treatment follow-up.
Clinical Impact and Expert Perspectives
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, emphasized the impact of CRSwNP on patients' daily lives, noting that obstructions lead to disturbances in smell, taste, sleep, pain and fatigue. He stated, "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, highlighted the burden experienced by patients with nasal polyps, including repeat surgeries and frequent use of high-dose oral corticosteroids. He added, "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."
Key Endpoints and Trial Design
The co-primary endpoints of the WAYPOINT trial included 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 as part of the daily Nasal Polyposis Symptom Diary. Key secondary endpoints encompassed loss of smell, improvements 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.
Tezepelumab: Mechanism of Action and Current Approvals
Tezepelumab is a first-in-class human monoclonal antibody that inhibits thymic stromal lymphopoietin (TSLP), a key epithelial cytokine involved in multiple inflammatory cascades associated with severe asthma and CRSwNP. It is currently approved for the treatment of severe asthma in the US, EU, Japan, and nearly 60 countries, available as a single-use pre-filled syringe and auto-injector for self-administration in the US and EU.
Implications for CRSwNP Treatment
Chronic rhinosinusitis with nasal polyps is characterized by persistent inflammation of the nasal mucosa and the development of benign growths called nasal polyps. Current treatments include intranasal and systemic corticosteroids, surgery, and biologics. The positive results from the WAYPOINT trial suggest that tezepelumab could provide a valuable new option for patients with severe CRSwNP, particularly those who do not respond adequately to existing therapies.
