Phase III Data Show Efficacy of Tezspire Treating Chronic Rhinosinusitis with Nasal Polyps
Phase III WAYPOINT trial shows Tezspire (tezepelumab) significantly reduces nasal polyp size and congestion severity in patients with severe, uncontrolled chronic rhinosinusitis with nasal polyps, while also decreasing the need for surgery and systemic glucocorticoids.
Credit: Prostock-studio | stock.adobe.com
Tezspire (tezepelumab-ekko; Amgen and AstraZeneca) was found to significantly decrease the size of nasal polyps while reducing congestion severity and patient-reported symptoms in patients with severe, uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP), according to results from the Phase III WAYPOINT trial (NCT04851964) published by The New England Journal of Medicine.1,2 Patients administered Tezspire also had a lesser need for surgery and use of systemic glucocorticoids compared to those given placebo, with no additional safety signals reported in the trial.
“Treatment with tezepelumab led to reductions in both coprimary end-point criteria (nasal-polyp size and nasal congestion) that were sustained through week 52 and resulted in significantly less nasal-polyp surgery and use of systemic glucocorticoids than placebo,” the study authors wrote. “Significant improvements were observed across all key secondary end points assessed in the overall trial population. 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.”1
Tezspire is a first-in-class human monoclonal antibody that acts on the airway epithelium, which is the primary cause of inflammation and the first point of contact for viruses, allergens, pollutants, and other environmental irritants. The medication inhibits the thymic stromal lymphopoietin (TSLP), which is an alarmin-class cytokine that acts in the early stages of the inflammatory process. The expression of TSLP is elevated in the airways of patients with asthma and is associated with disease severity.
Tezspire was initially approved in December 2021 as the only biologic indicated for severe asthma with no phenotype or biomarker limitation within its approved label. In February 2023, Tezspire was approved as a pre-filled, single-use pen for patients aged 12 years and older with severe asthma.3
CRSwNP is an inflammatory disorder involving persistent inflammation of the nasal mucosa along with nasal polyps. These polyps may block nasal passages, causing breathing issues, loss of or limited sense of smell, nasal discharge, facial pain, sleep disruption, as well as other adverse effects that inhibit quality of life (QoL).
Trial Design
The multicenter, randomized, double-blind, parallel-group, placebo-controlled trial randomly assigned 408 patients with physician-diagnosed, symptomatic, severe CRSwNP to compare outcomes with standard care and Tezspire (n = 203) administered at a dose of 210 mg or standard care and placebo (n = 205) administered subcutaneously every four weeks for 52 weeks.
The trial’s coprimary endpoints were change from baseline in total nasal-polyp score (range, 0 to 4 [for each nostril]) and mean nasal-congestion score (range, 0 to 3) after 52 weeks. Key secondary endpoints in the overall patient population included loss of smell; improvement in disease-specific health-related QoL as per SinoNasal Outcome Test score; Lund-Mackay score; time to surgery decision and/or systemic corticosteroids for nasal polyposis; time to nasal polyposis surgery decision; time to systemic corticosteroids for nasal polyposis; Nasal Polyposis Symptom Diary total symptom score and pre-bronchodilator FEV1 in trial participants with comorbid asthma and aspirin-exacerbated respiratory disease/non-steroidal anti-inflammatory-exacerbated respiratory disease at 52 weeks.
Topline data released in November 2024 showed a statistically significant and clinically meaningful decrease in nasal polyp size (mean difference vs. placebo, −2.07; 95% confidence interval [CI], −2.39 to −1.74) and reduced nasal congestion in patients administered Tezspire compared to placebo score (−1.03; 95% CI, −1.20 to −0.86) (P<0.001 for both scores).4
Tezspire was also found to significantly improve loss-of-smell score (mean difference vs. placebo, −1.00; 95% CI, −1.18 to −0.83), SNOT-22 total score (−27.26; 95% CI, −32.32 to −22.21), Lund–Mackay score (−5.72; 95% CI, −6.39 to −5.06), and total symptom score (−6.89; 95% CI, −8.02 to −5.76) (P<0.001 for all scores).
Further, 0.5% of patients in the Tezspire cohort required surgery for nasal polyps (0.5%) compared to 22.1% of patients in the placebo cohort (hazard ratio, 0.02; 95% CI, 0.00 to 0.09). Additionally, 5.2% of patients in the Tezspire cohort required use of systemic glucocorticoids compared to 18.3% of patients in the placebo cohort (hazard ratio, 0.12; 95% CI, 0.04 to 0.27) (P<0.001 for both time-to-event analyses).
“Treatment with systemic glucocorticoids and nasal-polyp surgery does not address the underlying inflammatory processes in patients with severe chronic rhinosinusitis with nasal polyps,” the study authors wrote. “Furthermore, long-term glucocorticoid use is associated with adverse side effects. However, biologic therapies have transformed approaches to treatment by directly addressing the underlying inflammatory mechanisms associated with severe chronic rhinosinusitis with nasal polyps.”1
References
1. Lipworth B., et al. Tezepelumab in Adults with Severe Chronic Rhinosinusitis with Nasal Polyps. N Engl J Med 2025. Published March 1, 2025. DOI: 10.1056/NEJMoa2414482
2. Efficacy and Safety of Tezepelumab in Participants With Severe Chronic Rhinosinusitis With Nasal Polyposis (WAYPOINT). ClinicalTrials.gov. Updated December 20, 2024. Accessed March 4, 2025. https://clinicaltrials.gov/study/NCT04851964
3. Tezspire approved for self-administration in the US with a new pre-filled pen. News release. Amgen; February 2, 2023. Accessed March 4, 2025. https://www.amgen.com/newsroom/press-releases/2023/02/tezspire-approved-for-self-administration-in-the-u-s--with-a-new-pre-filled-pen
4. Tezspire Met Both Co-Primary Endpoints In Phase 3 Trial For Chronic Rhinosinusitis With Nasal Polyps. News release. Amgen. November 7, 2024. Accessed March 4, 2025. https://www.amgen.com/newsroom/press-releases/2024/11/tezspire-met-both-co-primary-endpoints-in-phase-3-trial-for-chronic-rhinosinusitis-with-nasal-polyps
Xolair Outperforms Oral Immunotherapy in Landmark Phase III OUtMATCH Food Allergy Trial
March 3rd 2025Xolair (omalizumab) shows superior efficacy and safety compared to multi-allergen oral immunotherapy in treating food allergies in the Phase III OUtMATCH trial, suggesting the potential to facilitate the introduction of allergenic foods into patients' diets after treatment.
Symbravo Outperforms Oral CGRP Inhibitors in Phase III Trial, With Faster, Sustained Migraine Relief
February 24th 2025Data from the Phase III EMERGE trial show treatment with Symbravo provided more rapid and sustained migraine relief with improved quality of life in patients who previously had an inadequate response to CGRP treatments.
