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

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
 

Full results from the positive Phase III WAYPOINT trial showed AstraZeneca and Amgen’s Tezspire (tezepelumab) 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

*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.

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Notes

Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)
CRSwNP is a complex inflammatory disorder, characterised 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, randomised, 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

Tezepelumab
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 paediatric 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 U.S. Food and Drug Administration (FDA) for the treatment of EoE. In July 2024, the U.S. FDA granted a Breakthrough Therapy Designation for tezepelumab for the add-on maintenance treatment of patients with moderate to very severe COPD characterised 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 commercialise 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 (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit dlokoko.com and follow the Company on social media @AstraZeneca

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