Positive topline results from the Phase III WAYPOINT trial indicate that AstraZeneca and Amgen's Tezspire (tezepelumab) met both co-primary endpoints in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). The trial demonstrated a statistically significant and clinically meaningful reduction in nasal polyp size and nasal congestion compared to placebo, offering a potential new treatment avenue for this debilitating condition.
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.
Clinical Impact of Tezepelumab
Dr. Joseph Han, co-primary investigator and Vice Chair of Rhinology & Endoscopic Sinus and Skull Base Surgery, and Allergy, Otolaryngology-Head and Neck Surgery, Eastern Virginia Medical School, emphasized the impact of CRSwNP on patients' 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, co-primary investigator and Professor of Allergy and Pulmonology, Scottish Centre for Respiratory Research, highlighted the burden on patients, including repeat surgeries and frequent use of high-dose oral corticosteroids with systemic side effects. 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."
WAYPOINT Trial Design and Endpoints
The WAYPOINT trial featured a 52-week treatment period, followed by a post-treatment follow-up of 12-24 weeks for participants who completed the treatment phase. 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 as part of the daily Nasal Polyposis Symptom Diary.
Key secondary endpoints included assessments of 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, in patients with comorbid asthma, pre-bronchodilator FEV1 at Week 52.
Tezepelumab's 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 initiating and sustaining allergic, eosinophilic, and other types of airway inflammation associated with severe asthma, including airway hyperresponsiveness.
Sharon Barr, Executive Vice President, BioPharmaceuticals R&D at AstraZeneca, noted, "These results reinforce that 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."
Current Treatment Landscape for CRSwNP
CRSwNP is characterized by persistent inflammation of the nasal mucosa accompanied by benign growths (nasal polyps). Current treatments include intranasal and systemic corticosteroids, surgery, and biologics. Epithelial dysfunction and inflammation are key features of CRSwNP, impairing the epithelium's barrier function against the external environment.
Safety and Tolerability
The safety profile and tolerability of Tezspire in the WAYPOINT trial were consistent with the known profile of the medicine. Full results will be presented at an upcoming medical meeting and shared with regulatory authorities.
