SAN DIEGO — Tezepelumab (Tezspire) reduced nasal polyps and symptoms in severe chronic rhinosinusitis while also decreasing need for further treatments, the WAYPOINT trial showed.
The monoclonal antibody against thymic stromal lymphopoietin (TSLP) improved total nasal-polyp score by a mean -2.07 points (95% CI −2.39 to −1.74) more than placebo on a 0-4 point scale at 52 weeks, Joseph Han, MD, of Eastern Virginia Medical School in Norfolk, reported at the American Academy of Allergy, Asthma & Immunology annual meeting.
The coprimary endpoint of mean nasal-congestion score was improved by a mean of −1.03 more than placebo on a 0-3 point scale (95% CI −1.20 to −0.86) in the findings simultaneously published in the New England Journal of Medicine.
Subsequent nasal-polyp surgery and treatment with systemic glucocorticoids also significantly declined with tezepelumab treatment. Secondary endpoint results “show that the patients had clinically meaningful reductions in their symptoms and improvements in health-related quality of life,” the group wrote.
Previous findings from a pre-specified exploratory analysis of the pivotal NAVIGATOR asthma treatment trial had suggested a benefit of the epithelial cytokine blocker in patients with comorbid chronic rhinosinusitis with nasal polyps.
Building on that hypothesis, WAYPOINT findings “suggest that the reduction in multiple downstream inflammatory signaling may modify disease severity in the patients who participated in the present trial,” Han’s group wrote.
“The data look really impressive for nasal polyps,” agreed session panelist Thomas B. Casale, MD, of the University of South Florida in Tampa.
Monoclonal antibodies dupilumab (Dupixent), omalizumab (Xolair), and mepolizumab (Nucala) are already approved for treating chronic rhinosinusitis with nasal polyps, and “have shown various degrees of efficacy in patients with severe disease,” Han’s group noted. “There remains an unmet need for patients who have an inadequate response to these biologic agents.”
The phase III WAYPOINT trial included 408 adults with physician-diagnosed chronic rhinosinusitis with nasal polyps for at least 12 months that were severe enough to indicate surgery — a total endoscopic nasal-polyp score of at least 5 on an 8-point scale, with a minimum score of at least 2 for each nostril. Enrollment required documented symptoms ongoing for at least 8 weeks including a nasal-congestion score of at least 2 and a total score on the 22-item Sinonasal Outcome Test (SNOT-22) of at least 30 on the 110-point scale. Stable standard-care treatment for at least 30 days along with documented systemic glucocorticoid treatment in the previous 12 months or prior nasal polyp surgery of any type were also required for entry into the trial.
Participants were randomly assigned to receive standard care and either tezepelumab (210 mg) or placebo subcutaneously every 4 weeks for 52 weeks.
“No new safety concerns were identified in this trial with the use of the licensed tezepelumab dose of 210 mg for severe asthma, for which the safety and side-effect profiles are well documented,” the researchers noted.
In terms of efficacy, high blood eosinophils predicted greater benefit of tezepelumab but those without them still showed significant symptom improvement over placebo, Han noted at the late-breaking trial session. Given a number of choices in the field, selection of one biologic over another would likely follow patient preferences, prioritizing oral medications and longer-interval injections, he predicted.
How the drugs’ mechanisms impact atopic disease is still being plumbed.
“You have tezepelumab fail in atopic dermatitis, fail in urticaria — both [type 2 inflammation] driven diseases, if you would,” Casale said, contrasting it with the nasal polyp findings. “What kind of hints is this giving us about the role of TSLP in these disorders and how that is different in the upper airway?”
“These clinical studies that we do help us understand the mechanism of how the disease works,” Han responded. “So in those studies for urticaria, it clearly tells us that certain markers are more important in a certain disease, and targeting that makes sense. There may be some redundancy [such that] you might target one specific molecule and it may not be enough.”
Disclosures
WAYPOINT was funded by AstraZeneca and Amgen. Some co-authors are employees of AstraZeneca or Amgen.
Han disclosed relationships with AstraZeneca, GSK, Regeneron, and Sanofi.
Primary Source
New England Journal of Medicine
Source Reference: Lipworth BJ, et al “Tezepelumab in adults with severe chronic rhinosinusitis with nasal polyps” N Engl J Med 2025; DOI: 10.1056/NEJMoa2414482.
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