Positive results from the TEZSPIRE Phase III WAYPOINT trial highlight rapid and sustained effect in chronic rhinosinusitis with nasal polyps

Rhea-AI Summary

TEZSPIRE demonstrated significant positive results in its Phase III WAYPOINT trial for treating chronic rhinosinusitis with nasal polyps (CRSwNP). The trial showed the drug reduced nasal polyp severity and nasal congestion compared to placebo, with improvements observed as early as week two and sustained through week 52.

Key findings include a 98% reduction in the need for nasal polyp surgery and an 88% reduction in systemic corticosteroid treatment requirements. The drug achieved statistically significant improvements in Nasal Polyp Score (-2.065) and Nasal Congestion Score (-1.028) at week 52.

The treatment was generally well tolerated, with common adverse events including COVID-19, nasopharyngitis, and upper respiratory tract infection. The safety profile aligned with its approved severe asthma indication. Regulatory filings for TEZSPIRE in CRSwNP are currently under review in multiple regions.

Positive

• 98% reduction in need for nasal polyp surgery
• 88% reduction in systemic corticosteroid use
• Significant improvement in nasal polyp score (-2.065)
• Rapid onset of action (2-4 weeks)
• Sustained efficacy through 52 weeks

Negative

• Multiple adverse events reported including COVID-19 and respiratory infections
• Still pending regulatory approval for CRSwNP indication

Insights

Financial Analyst

The positive Phase III WAYPOINT trial results for TEZSPIRE represent a significant potential revenue catalyst for AstraZeneca and its partner Amgen. The remarkably strong efficacy data - including a 98% reduction in need for nasal polyp surgery and 88% reduction in systemic corticosteroid use - positions TEZSPIRE as a potentially disruptive therapy in the chronic rhinosinusitis with nasal polyps (CRSwNP) market.

This label expansion opportunity is particularly valuable as it leverages an already commercialized asset with established manufacturing and marketing infrastructure. The CRSwNP indication would significantly expand TEZSPIRE's addressable patient population beyond its current severe asthma approval in 60+ countries, potentially accelerating the drug's growth trajectory.

The strength of these results, published in the prestigious New England Journal of Medicine, suggests TEZSPIRE could potentially capture substantial market share from existing biologics in this space including Dupixent, Xolair and Nucala. The first-in-class mechanism targeting TSLP provides further differentiation in a competitive landscape.

With regulatory filings already under review in multiple regions, approval for this new indication could materialize within 6-12 months, creating a near-term revenue inflection point. This expansion also validates AstraZeneca's broader respiratory and immunology strategy, suggesting additional indications like COPD and eosinophilic esophagitis (both in development) may hold similar promise.

Medical Expert

The WAYPOINT trial results for tezepelumab in chronic rhinosinusitis with nasal polyps demonstrate remarkable clinical efficacy that exceeds typical expectations for biologics in this therapeutic area. The near-elimination of need for subsequent surgery (98% reduction) is particularly noteworthy, as surgical intervention has been a mainstay treatment for this condition.

The rapid onset of effect (improvements in nasal polyp score as early as week 4 and nasal congestion score by week 2) addresses a significant unmet need, as patients with CRSwNP often endure prolonged symptomatic periods before experiencing relief with current therapies. The sustained efficacy through 52 weeks further demonstrates tezepelumab's potential as a disease-modifying therapy.

TEZSPIRE's mechanism targeting thymic stromal lymphopoietin (TSLP) represents a novel approach in CRSwNP treatment. By inhibiting this key epithelial cytokine at the top of multiple inflammatory cascades, tezepelumab appears to provide comprehensive suppression of the inflammatory processes driving polyp formation and symptoms.

The safety profile, consistent with its established profile in severe asthma, suggests minimal additional risk concerns for this new indication. This favorable benefit-risk profile, combined with the 88% reduction in systemic corticosteroid use, addresses serious clinical concerns about long-term corticosteroid toxicity that affects many CRSwNP patients. If approved, TEZSPIRE would offer a compelling alternative to existing biologics and potentially become a preferred option for many patients with inadequate response to standard treatments.

TEZSPIRE significantly reduced nasal congestion, polyp size and nearly eliminated the need for surgery in patients with chronic rhinosinusitis with nasal polyps

WAYPOINT data published in New England Journal of Medicine and highlighted as late-breaking oral presentation at AAAAI/WAO 2025

WILMINGTON, Del.--(BUSINESS WIRE)-- Full results from the positive Phase III WAYPOINT trial showed AstraZeneca and Amgen’s TEZSPIRE^® (tezepelumab-ekko) significantly reduced nasal polyp severity, the need for subsequent surgery, and systemic corticosteroid use in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) compared to placebo.^1,2 These data were published in the New England Journal of Medicine and presented today as a late-breaking oral presentation at the American Academy of Allergy Asthma & Immunology (AAAAI)/World Allergy Organization (WAO) Joint Congress in San Diego, CA.^1,2

Treatment with TEZSPIRE significantly reduced nasal polyp severity measured by the co-primary endpoints; Nasal Polyp Score (NPS) by -2.065 (95% CI: -2.389, -1.742; p<0.0001) and nasal congestion (measured by participant-reported Nasal Congestion Score [NCS]) by -1.028 (95% CI: -1.201, -0.855; p<0.0001) at week 52 compared to placebo.^1,2 Improvements in NPS were observed as early as week four and NCS as early as week two (the first post-treatment assessment respectively) and were sustained through week 52.¹

Statistically significant and clinically meaningful improvements were observed across all key secondary outcomes assessed in the overall trial population.¹ Importantly, TEZSPIRE significantly reduced the need for subsequent nasal polyp surgery by 98% (p<0.0001) and the need for systemic corticosteroid treatment by 88% ( p<0.0001) compared to placebo.¹

Dr Joseph Han, Vice Chair of Department of Otolaryngology - Head and Neck Surgery, Old Dominion University, US, and co-primary investigator in the trial, said: “Many patients living with nasal polyps are at risk of repeat surgeries and serious systemic side effects from long-term oral corticosteroids. 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.”

Sharon Barr, Executive Vice President, BioPharmaceuticals R&D said, “The WAYPOINT results demonstrate the potential for TEZSPIRE to provide a much-needed option for patients with chronic rhinosinusitis with nasal polyps. With its first-in-class mode of action, targeting TSLP at the top of the inflammatory cascade, the data add to the body of evidence that tezepelumab can transform care for patients with epithelial-driven inflammatory diseases.”

Table M1: Summary of co-primary and key secondary efficacy endpoints^1,2

Endpoint	Tezepelumab (n=203)	Placebo (n=205)	Difference vs. Placebo (95% CI)
Co-primary endpoints
Total nasal polyp score (range 0-8)*	-2.458 (0.114)	-0.392 (0.118)	-2.065 (-2.389, -1.742) p<0.0001**
Nasal congestion score (range 0-3)*	-1.743 (0.062)	-0.715 (0.064)	-1.028 (-1.201, -0.855) p<0.0001**
Key secondary endpoints Assessed in the overall trial population
Time to first nasal polyp surgery decision (% patients)***	0.5 (0.0, 2.5)	22.1 (16.4, 28.2)	0.02 (0.00, 0.09) p<0.0001**
Time to first systemic glucocorticoid use (% patients)***	5.2 (1.1, 14.7)	18.3 (13.3, 24.1)	0.12 (0.04, 0.27) p<0.0001**
Time to nasal polyp surgery decision and/or systemic glucocorticoid use (% patients)***	5.7 (1.3, 15.0)	30.6 (24.2, 37.1)	0.08 (0.03, 0.17) p<0.0001**
Loss of smell score (range 0-3)*	-1.26 (0.06)	-0.26 (0.06)	-1.00 (-1.18, -0.83) p<0.0001**
Sino-Nasal Outcome Test-22 (SNOT-22) total score (range 0-110)*	-45.02 (1.81)	-17.76 (1.84)	-27.26 (-32.32, -22.21) p<0.0001**
Sinus Computed Tomography Lund–Mackay (CT-LMK) score (range 0-24)*	-6.27 (0.24)	-0.55 (0.24)	-5.72 (-6.39, -5.06) p<0.0001**
Total Symptom Score (TSS) (range 0-24)*	-10.39 (0.40)	-3.50 (0.41)	-6.89 (-8.02, -5.76) p<0.0001**
Key secondary endpoint Assessed in a subset of patients with co-morbid asthma or nonsteroidal anti-inflammatory drug exacerbated respiratory disease
Pre-bronchodilator forced expiratory volume in 1 second (FEV1 in liters)*	0.02 (0.04)	0.03 (0.04)	-0.01 (-0.12, 0.11) p=0.9362
*LS mean change (SE) from baseline at Week 52
**Denotes statistically significant at 0.01 level after adjustment for multiplicity. Unadjusted P-values are presented
*** % patients from Kaplan Meier estimate (95% confidence interval) is provided for each treatment group, hazard ratio (95% confidence interval) is presented for the difference vs placebo.

TEZSPIRE was generally well tolerated in patients with CRSwNP and had a safety profile consistent with its approved severe asthma indication.^1,2 The most frequently reported adverse events for TEZSPIRE in the WAYPOINT trial were COVID-19, nasopharyngitis and upper respiratory tract infection.¹ There were no clinically meaningful differences in safety results between the TEZSPIRE and placebo group.¹

TEZSPIRE is currently approved for the treatment of severe asthma in the US, EU, Japan, and over 60 countries across the globe.^3-5 It is approved as a single-use pre-filled syringe and auto-injector for self-administration in the US and EU.^3,4 Regulatory filings for tezepelumab in CRSwNP are currently under review by regulatory authorities in multiple regions.

INDICATION AND LIMITATION OF USE / ISI

TEZSPIRE^® (tezepelumab-ekko)

INDICATION

TEZSPIRE is indicated for the add-on maintenance treatment of adult and pediatric patients aged 12 years and older with severe asthma.

TEZSPIRE is not indicated for the relief of acute bronchospasm or status asthmaticus.

CONTRAINDICATIONS

Known hypersensitivity to tezepelumab-ekko or excipients.

WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions

Hypersensitivity reactions were observed in the clinical trials (eg, rash and allergic conjunctivitis) following the administration of TEZSPIRE. Postmarketing cases of anaphylaxis have been reported. These reactions can occur within hours of administration, but in some instances have a delayed onset (ie, days). In the event of a hypersensitivity reaction, consider the benefits and risks for the individual patient to determine whether to continue or discontinue treatment with TEZSPIRE.

Acute Asthma Symptoms or Deteriorating Disease

TEZSPIRE should not be used to treat acute asthma symptoms, acute exacerbations, acute bronchospasm, or status asthmaticus.

Abrupt Reduction of Corticosteroid Dosage

Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with TEZSPIRE. Reductions in corticosteroid dose, if appropriate, should be gradual and performed under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.

Parasitic (Helminth) Infection

It is unknown if TEZSPIRE will influence a patient’s response against helminth infections. Treat patients with pre-existing helminth infections before initiating therapy with TEZSPIRE. If patients become infected while receiving TEZSPIRE and do not respond to anti-helminth treatment, discontinue TEZSPIRE until infection resolves.

Live Attenuated Vaccines

The concomitant use of TEZSPIRE and live attenuated vaccines has not been evaluated. The use of live attenuated vaccines should be avoided in patients receiving TEZSPIRE.

ADVERSE REACTIONS

The most common adverse reactions (incidence ≥3%) are pharyngitis, arthralgia, and back pain.

USE IN SPECIFIC POPULATIONS

There are no available data on TEZSPIRE use in pregnant women to evaluate for any drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Placental transfer of monoclonal antibodies such as tezepelumab-ekko is greater during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy.

Please see full Prescribing Information, including Patient Information and Instructions for Use.

You may report side effects related to AstraZeneca products.

Notes

Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)

CRSwNP is a complex inflammatory disorder, characterized by persistent inflammation of the nasal mucosa accompanied by benign growths, called nasal polyps.^6,7 Nasal polyps and the accompanying inflammation can block nasal passages and lead to breathing problems, difficulty in sense of smell, nasal discharge, facial pain, sleep disturbance and other adverse effects on quality of life.^8-10 Current treatments for CRSwNP include intranasal and/or systemic corticosteroids, surgery and biologics.^7,10-16

Phase III WAYPOINT trial

WAYPOINT was a double-blind, multi-centre, randomized, placebo-controlled, parallel group trial designed to evaluate the efficacy and safety of tezepelumab in adults with severe CRSwNP.^1,2,17 Participants received tezepelumab or placebo, administered via subcutaneous injection.^1,2,17 The trial also included a post-treatment follow-up period of 12-24 weeks for participants who completed the 52-week treatment period.^1,17

TEZSPIRE

TEZSPIRE^® (tezepelumab) is being developed by AstraZeneca in collaboration with Amgen as a first-in-class human monoclonal antibody that inhibits the action of thymic stromal lymphopoietin (TSLP), a key epithelial cytokine that sits at the top of multiple inflammatory cascades and is critical in the initiation and persistence of allergic, eosinophilic, and other types of epithelial-driven inflammation associated with severe asthma and other inflammatory diseases.^18,19

TSLP is released in response to multiple epithelial triggers and insults (including allergens, viruses, bacteria, smoke, air pollution and other airborne particles) associated with asthma, CRSwNP, chronic obstructive pulmonary disease (COPD), eosinophilic esophagitis (EoE) and other diseases.^19,20 Expression of TSLP is increased in these patients and has been correlated with disease severity.^10,18 Blocking TSLP can prevent the release of pro-inflammatory cytokines by immune cells, resulting in the prevention of exacerbations and improved disease control.^18,19,21 Tezepelumab acts at the top of the inflammatory cascade and research indicates that targeting TSLP released by the airway and gastrointestinal epithelium may be a potential approach to treating other diseases in the future.^18,22,23

TEZSPIRE is approved in the US, the EU and over 60 countries for the add-on maintenance treatment of adult and pediatric patients aged 12 years and older with severe asthma.^3-5

Beyond CRSwNP, tezepelumab is also in development for other potential indications including COPD and EoE.^24,25 In October 2021, tezepelumab was granted Orphan Drug Designation by the US Food and Drug Administration (FDA) for the treatment of EoE. In July 2024, the US FDA granted a Breakthrough Therapy Designation for tezepelumab for the add-on maintenance treatment of patients with moderate to very severe COPD characterized by an eosinophilic phenotype.

Amgen collaboration

In 2020, Amgen and AstraZeneca updated a 2012 collaboration agreement for TEZSPIRE. Both companies will continue to share costs and profits equally after payment by AstraZeneca of a mid-single-digit inventor royalty to Amgen. AstraZeneca continues to lead development, and Amgen continues to lead manufacturing. All aspects of the collaboration are under the oversight of joint governing bodies. Under the amended agreement, Amgen and AstraZeneca will jointly commercialize TEZSPIRE in North America. Amgen will record product sales in the US, with AZ recording its share of US profits as Collaboration Revenue. Outside of the US, AstraZeneca will record product sales, with Amgen recording profit share as Other/Collaboration revenue.

AstraZeneca in Respiratory & Immunology

Respiratory & Immunology, part of AstraZeneca BioPharmaceuticals is a key disease area and growth driver to the Company.

AstraZeneca is an established leader in respiratory care with a 50-year heritage and a growing portfolio of medicines in immune-mediated diseases. The Company is committed to addressing the vast unmet needs of these chronic, often debilitating, diseases with a pipeline and portfolio of inhaled medicines, biologics and new modalities aimed at previously unreachable biologic targets. Our ambition is to deliver life-changing medicines that help eliminate COPD as a leading cause of death, eliminate asthma attacks and achieve clinical remission in immune-mediated diseases.

AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 125 countries, and its innovative medicines are used by millions of patients worldwide. Please visit www.astrazeneca-us.com and follow the Company on social media @AstraZeneca

References

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2. Lipworth, BJ, Han JK, et al. Efficacy and safety of tezepelumab in adults with severe chronic rhinosinusitis with nasal polyps: results from the Phase 3 WAYPOINT Study. [Late breaking oral presentation]. Presented at the American Academy of Allergy, Asthma & Immunology /World Allergy Organization Joint Congress 2025 (28 February – 03 March).
3. TEZSPIRE (tezepelumab) US prescribing information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761224s003lbl.pdf. [Last accessed: February 2025].
4. TEZSPIRE (tezepelumab) Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/tezspire-epar-product-information_en.pdf. [Last accessed: February 2025].
5. AstraZeneca plc. TEZSPIRE approved in Japan for the treatment of severe asthma. Available at: https://www.astrazeneca.com/media-centre/press-releases/2022/tezspire-approved-in-japan-for-severe-asthma.html. [Last accessed: February 2025].
6. Bachert C, et al. Phenotypes and Emerging Endotypes of Chronic Rhinosinusitis. J Allergy Clin Immunol Pract. 2016; 4 (4): 621-628.
7. Del Toro E, Portela J. Nasal Polyps. [Updated 2023 Jul 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560746/ [Last accessed: February 2025].
8. Stevens WW, et al. Chronic Rhinosinusitis with Nasal Polyps. J Allergy Clin Immunol Pract. 2016; 4 (4): 565-572.
9. Abdalla S, et al. Prevalence of sinonasal outcome test (SNOT-22) symptoms in patients undergoing surgery for chronic rhinosinusitis in the England and Wales National prospective audit. Clin Otolaryngol. 2012; 37 (4): 276-282.
10. Chen S et al. Systematic literature review of the epidemiology and clinical burden of chronic rhinosinusitis with nasal polyposis. Curr Med Res Opin. 2020;36(11):1897-1911.
11. Xolair (omalizumab) Summary of Product Characteristics; Available at: https://www.ema.europa.eu/en/documents/product-information/xolair-epar-product-information_en.pdf. [Last accessed: February 2025].
12. Xolair (omalizumab) US prescribing information; Available at: https://www.gene.com/download/pdf/xolair_prescribing.pdf [Last accessed: February 2025].
13. Nucala (mepolizumab) Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/nucala-epar-product-information_en.pdf. [Last accessed: February 2025].
14. Nucala (mepolizumab) US prescribing information; Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761122s006,125526s018lbl.pdf. [Last accessed: February 2025].
15. Dupixent (dupilumab) Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/dupixent-epar-product-information_en.pdf. [Last accessed: February 2025].
16. Dupixent (dupilumab) US prescribing information; Available at: https://www.regeneron.com/downloads/dupixent_fpi.pdf. [Last accessed: February 2025].
17. Clinicaltrials.gov. Efficacy and Safety of Tezepelumab in Participants With Severe Chronic Rhinosinusitis With Nasal Polyposis (WAYPOINT). Available at: https://clinicaltrials.gov/ct2/show/NCT04851964. [Last accessed: February 2025].
18. Corren J, et al. Tezepelumab in adults with uncontrolled asthma. N Engl J Med. 2017;377:936-946.
19. Varricchi G, et al. Thymic Stromal Lymphopoietin Isoforms, Inflammatory Disorders, and Cancer. Front Immunol. 2018;9:1595.
20. Zhang M, et al. Hypoxia induces the production of epithelial-derived cytokines in eosinophilic chronic rhinosinusitis with nasal polyps. Int Immunopharmacol. 2023;121:110559.
21. Li Y, et al. Elevated Expression of IL-33 and TSLP in the Airways of Human Asthmatics In Vivo: A Potential Biomarker of Severe Refractory Disease. J Immunol. 2018;200: 2253–2262.
22. Menzies-Gow A, et al. Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma. N Engl J Med. 2021;384:1800-1809.
23. Laidlaw TM et al. Tezepelumab Efficacy in Patients with Severe, Uncontrolled Asthma with Comorbid Nasal Polyps in NAVIGATOR. J Asthma Allergy. 2023 Sep 4:16:915-932.
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FAQ

What were the main efficacy results of TEZSPIRE in the WAYPOINT Phase III trial for nasal polyps?

TEZSPIRE reduced nasal polyp severity (NPS) by -2.065 and nasal congestion by -1.028 at week 52 vs placebo, with improvements seen as early as weeks 2-4.

How much did TEZSPIRE reduce the need for surgery and corticosteroids in CRSwNP patients?

TEZSPIRE reduced the need for nasal polyp surgery by 98% and systemic corticosteroid treatment by 88% compared to placebo.

What were the most common side effects reported in the TEZSPIRE WAYPOINT trial?

The most frequent adverse events were COVID-19, nasopharyngitis and upper respiratory tract infection.

When did improvements begin showing in patients taking TEZSPIRE for nasal polyps?

Improvements were observed as early as week two for nasal congestion and week four for nasal polyp score, sustaining through week 52.