Tezepelumab Reduces Nasal Polyp Severity in Severe CRSwNP During Phase 3 Trial

The phase 3 WAYPOINT study found tezepelumab significantly reduced nasal polyp severity and the need for nasal polyp surgery for patients with severe chronic rhinosinusitis.1 The findings are presented as a late breaker at the 2025 American Academy of Allergy, Asthma, & Immunology (AAAAI) annual meeting.

Tezeplumab, approved by the US Food and Drug Administration) in February 2023 for self-administration of a pre-filled, single-use pen for patients with severe asthma, is currently being investigated as a treatment for severe chronic rhinosinusitis with nasal polyps (CRSwNP).1,2 In the phase 3 randomized WAYPOINT trial, investigators, led by Joseph Han, MD, FAAAAI, from Eastern Virginia Medical School, sought to assess the efficacy and safety of tezepelumab—a human monoclonal antibody that blocks the activity of an upstream thymic stromal lymphopoietin—in adults with severe CRSwNP.1

WAYPOINT’s primary endpoints included a change from baseline in total nasal polyp score and bi-weekly mean nasal congestion score at week 52. Secondary endpoints included self-reported loss of smell, SNOT-22 total score, Lund-Mackay score, total symptom score, and time-to-first nasal polyp surgery decision or systemic corticosteroid treatment for CRSwNP.

Adults with CRSwNP were randomized 1:1 to tezepelumab 210 mg (n = 5203) or placebo (n = 5205) subcutaneously every 4 weeks for 52 weeks. Compared with placebo, participants on tezepelumab significantly improved total nasal polyp (least squares mean difference, 22.101; 95% confidence interval [CI], 22.414 – 21.788; P < .0001) and mean nasal congestion score (mean difference, 21.088; 95% CI, 21.261 – 20.915; P < .0001) at week 52 compared with placebo. The team observed improvements in nasal polyp and mean nasal congestion scores at weeks 2 and 4 post-treatment (P < .01).

At week 52, tezepelumab brought significant improvements compared with placebo in loss of smell (mean difference, 21.033; 95% CI, 21.204 – 20.863), SNOT-22 score (mean difference, 228.434; 95% CI, 233.485 – 223.383), Lund-Mackay score (mean difference, 25.392; 95% CI, 26.098 – 24.687), and total symptom score (mean difference, 27.235; 95% CI, 28.365 – 26.105) (all P < .0001).

In WAYPOINT, tezepelumab decreased the need for nasal polyp surgery or systemic corticosteroid treatment by 92% compared with placebo (hazard ratio [HR], 0.08; 95% CI, 0.03 – 0.17). Adverse event rates were similar between arms.

“Tezepelumab significantly reduced [nasal polyp] severity and the need for NP surgery or SCS, and improved patient-reported sino-nasal symptoms versus placebo in adults with severe CRSwNP,” investigators concluded.

References

1. Han, J, Lipworth, B, Desrosiers, M, et al. Efficacy And Safety Of Tezepelumab In Adults With Severe Chronic Rhinosinusitis With Nasal Polyps: Results From The Phase 3 WAYPOINT Study. Late-breaker presented at the 2025 AAAAI annual meeting in San Diego from February 28 to March 3.

2. Iapoce, C. FDA Approves Tezepelumab Self-Administration for Severe Asthma. HCPLive. February 2, 2023. https://www.hcplive.com/view/fda-approves-tezepelumab-self-administration-severe-asthma. Accessed February 21, 2025.