Tezepelumab-Ekko Reduces Nasal Polyp Severity and Need for Surgery in Patients With CRSWNP

Key Takeaways

Tezepelumab significantly reduced nasal polyp severity, surgery need, and corticosteroid use in CRSWNP patients compared to placebo in the phase 3 WAYPOINT trial.
The trial demonstrated significant improvements in nasal polyp and congestion scores, loss of smell, and quality of life measures.
Tezepelumab targets thymic stromal lymphopoietin (TSLP), addressing inflammation at the epithelial level, offering potential lasting relief for CRSWNP patients.
Adverse events were similar between treatment and placebo groups, with common issues including pharyngitis, arthralgia, and back pain.

Tezepelumab demonstrated efficacy compared with placebo when treating patients with chronic rhinosinusitis with nasal polyps.

Findings from the phase 3 WAYPOINT clinical trial (NCT04851964), published in The New England Journal of Medicine, demonstrated that tezepelumab-ekko (Tezspire; AstraZeneca, Amgen) significantly reduced nasal polyp severity, the need for surgery, and systemic corticosteroid use in patients with chronic rhinosinusitis with nasal polyps (CRSWNP) when compared with placebo. These data were presented as a late-breaking oral presentation during the 2025 American Academy of Allergy Asthma & Immunology (AAAAI)/World Allergy Organization (WAO) Joint Congress in San Diego, which was held February 28 through March 3.¹

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Tezepelumab is a first-in-class human monoclonal antibody that works on the primary source of inflammation—the airway epithelium—which is the first point of contact for viruses, allergens, pollutants, and other environmental insults. Specifically, tezepelumab targets and blocks thymic stromal lymphopoietin (TSLP), a key epithelial cytokine that sits at the top of multiple inflammatory cascades and initiates an overreactive immune response to allergic, eosinophilic, and other types of airway inflammation associated with severe asthma. TSLP is released in response to multiple triggers that are associated with asthma exacerbations, including allergens, viruses, and other airborne particles.¹

Tezepelumab is indicated for the add-on maintenance treatment of adult and pediatric patients aged 12 years and older with severe asthma. It is not currently indicated for the relief of acute bronchospasm or status asthmaticus, and it should not be used to treat acute asthma symptoms, acute exacerbations, acute bronchospasm, or status asthmaticus.¹

WAYPOINT (NCT04851964)² was a double-blind, multicenter, randomized, placebo-controlled, parallel group phase 3 trial designed to evaluate the efficacy and safety of tezepelumab in adults with severe CRSWNP. Patients were randomly assigned to receive tezepelumab (n = 203) or placebo (n = 205), administered via subcutaneous injection. The trial also included a post-treatment follow-up period of 12 to 24 weeks for participants who completed the 52-week treatment period.^1-3

The coprimary end points of the trial were change from baseline in total nasal polyp size—measured by the endoscopic total Nasal Polyp Score—and change from baseline in biweekly mean nasal congestion, measured by the participant-reported Nasal Congestion Score evaluated as part of the daily Nasal Polyposis Symptom Diary. Key secondary end points assessed in the overall population were the loss-of-smell score, the total score on the Sinonasal Outcome Test (SNOT-22; range: 0-110), the Lund–Mackay score (range: 0-24), the total symptom score (range: 0-24), and the first decision to treat with nasal-polyp surgery or use of systemic glucocorticoid therapy, or both, assessed in time-to-event analyses (individual and composite).^2,3

At week 52, patients receiving tezepelumab had significant improvements in the total nasal-polyp score compared with placebo (mean difference: −2.07; 95% CI, −2.39 to −1.74) and the mean nasal-congestion score (mean difference: −1.03; 95% CI, −1.20 to −0.86; P < .001). Additionally, tezepelumab significantly improved the loss-of-smell (−1.00; 95% CI, −1.18 to −0.83), SNOT-22 (−27.26; 95% CI, −32.32 to −22.21), Lund–Mackay (−5.72; 95% CI, −6.39 to −5.06), and symptom total scores (−6.89; 95% CI, −8.02 to −5.76).³

Further, surgery for nasal polyps was observed in significantly fewer patients in the tezepelumab group (0.5%) compared with the placebo group (22.1%) (HR: 0.02; 95% CI, 0.00 to 0.09). There was significantly less use of systemic glucocorticoids with tezepelumab (5.2%) than with placebo (18.3%) (HR: 0.12; 95% CI, 0.04 to 0.27).³

"Chronic rhinosinusitis with nasal polyps is a recurrent condition often requiring repeat courses of systemic corticosteroids, even for patients on currently available biologics, and can require repeat surgeries," said Jay Bradner, MD, executive vice president of Research and Development at Amgen, in a news release. "The WAYPOINT data highlight the potential of targeting inflammation at the epithelium to provide lasting relief for those with CRSWNP, adding to the efficacy profile that has been well established for [tezepelumab] in severe asthma."¹

About the Trial

Trial Name: Efficacy and Safety of Tezepelumab in Participants With Severe Chronic Rhinosinusitis With Nasal Polyposis (WAYPOINT)

ClinicalTrials.gov ID: NCT04851964

Sponsor: AstraZeneca

Completion Date: December 11, 2024

Adverse events (AEs) occurred in approximately 78.3% (n = 159) and 77.1% (n = 158) of patients in the tezepelumab and placebo groups, respectively.³ The most common AEs reported by patients treated with tezepelumab are pharyngitis, arthralgia, and back pain.¹ In the study, the most frequently reported AEs were COVID-19, nasopharyngitis, upper respiratory tract infection, headache, epistaxis, and worsening of chronic rhinosinusitis with nasal polyps.³

"Many patients living with nasal polyps are at risk of repeat surgeries and serious systemic side effects from long-term oral corticosteroids," coprimary investigator Joseph Han, MD, FARS, FAAOA, vice chair of rhinology & endoscopic sinus and skull base surgery, and allergy, otolaryngology-head and neck surgery, Eastern Virginia Medical School, said in the news release. "The WAYPOINT results are clinically meaningful and suggest that [tezepelumab] could greatly reduce the burden of nasal polyps for patients by nearly eliminating the need for future surgery and corticosteroid use and by significantly reducing nasal polyp size and congestion."¹

REFERENCES

1. Amgen. Positive results from the Tezspire® (tezepelumab-ekko) phase 3 WAYPOINT trial highlight rapid, sustained effect in chronic rhinosinusitis with nasal polyps. News release. March 1, 2025. Accessed March 3, 2025. https://www.amgen.com/newsroom/press-releases/2025/03/positive-results-from-tezspire-tezepelumabekko-phase-3-waypoint-trial-highlight-rapid-sustained-effect-in-chronic-rhinosinusitis-with-nasal-polyps

2. Efficacy and Safety of Tezepelumab in Participants With Severe Chronic Rhinosinusitis With Nasal Polyposis (WAYPOINT). ClinicalTrials.gov identifier: NCT04851964. Updated December 20, 2024. Accessed March 3, 2025. https://clinicaltrials.gov/study/NCT04851964

3. Lipworth BJ, Han JK, Besrosiers M, et al. Tezepelumab in Adults with Severe Chronic Rhinosinusitis with Nasal Polyps. NEJM. Published online: March 1, 2025. doi:10.1056/NEJMoa2414482