TEZSPIRE met both co-primary endpoints in the Phase III WAYPOINT trial in patients with chronic rhinosinusitis with nasal polyps

Rhea-AI Summary

AstraZeneca and Amgen's TEZSPIRE demonstrated positive results in the Phase III WAYPOINT trial for chronic rhinosinusitis with nasal polyps (CRSwNP). The trial showed statistically significant and clinically meaningful reduction in nasal polyp size and nasal congestion compared to placebo. The study evaluated TEZSPIRE's efficacy and safety when administered subcutaneously to adults with severe CRSwNP who remained symptomatic despite standard treatment. The safety profile was consistent with previous findings. TEZSPIRE is currently approved for severe asthma treatment in the US, EU, Japan, and nearly 60 countries globally.

Positive

• Phase III WAYPOINT trial met both co-primary endpoints
• Demonstrated significant reduction in nasal polyp size
• Showed meaningful improvement in nasal congestion
• Safety profile consistent with known profile
• Potential expansion of TEZSPIRE's approved indications beyond asthma

Negative

• None.

Insights

Medical Research Analyst

The successful Phase III WAYPOINT trial represents a significant milestone for AstraZeneca's TEZSPIRE in treating chronic rhinosinusitis with nasal polyps (CRSwNP). The drug met both co-primary endpoints with statistically significant and clinically meaningful results in reducing nasal polyp size and nasal congestion.

This expansion into CRSwNP treatment could substantially broaden TEZSPIRE's market reach beyond its current severe asthma indication. The positive results suggest potential for a new revenue stream in a market where few effective treatments exist. With TEZSPIRE already approved in nearly 60 countries for severe asthma, this additional indication could drive significant growth.

The consistent safety profile and strong efficacy data position TEZSPIRE favorably for regulatory approval in this new indication, potentially providing AstraZeneca with a competitive advantage in the CRSwNP treatment landscape.

TEZSPIRE demonstrated a statistically significant and clinically meaningful reduction in nasal polyp size and reduced nasal congestion compared to placebo

WILMINGTON, Del.--(BUSINESS WIRE)-- Positive high-level results from the Phase III WAYPOINT trial in patients with chronic rhinosinusitis with nasal polyps (CRSwNP [nasal polyps]) showed that AstraZeneca and Amgen’s TEZSPIRE^® (tezepelumab) demonstrated a statistically significant and clinically meaningful reduction in the size of nasal polyps and reduced nasal congestion compared to placebo.

WAYPOINT is a randomized, double-blind trial that evaluated the efficacy and safety of TEZSPIRE administered subcutaneously compared to placebo in adults with severe CRSwNP. Participants in the trial were symptomatic despite treatment with standard of care (intranasal corticosteroids [INCS]).¹

Dr. Joseph Han, Vice Chair of Rhinology & Endoscopic Sinus and Skull Base Surgery, and Allergy, Otolaryngology-Head and Neck Surgery, Eastern Virginia Medical School, US, and co-primary investigator in the trial, said: “Chronic rhinosinusitis with nasal polyps negatively impact patients’ daily lives with obstructions leading to disturbances in smell, taste and sleep as well as pain and fatigue. The impressive data from the WAYPOINT trial demonstrate tezepelumab’s potential as a new treatment for patients whose lives are disrupted by this debilitating disease.”

Dr. Brian Lipworth, Professor of Allergy and Pulmonology, Scottish Centre for Respiratory Research, and Tayside Rhinology Ear, Nose and Throat Clinic, Ninewells Hospital University of Dundee in Scotland, UK, and co-primary investigator in the trial, said: “Patients diagnosed with nasal polyps continue to experience significant burden including repeat surgeries and frequent treatment with high doses of oral corticosteroids, which are associated with serious systemic side effects. The tezepelumab data are clinically meaningful and offer patients with nasal polyps hope for a potential new treatment option that may reduce the burden on patients and healthcare systems.”

Sharon Barr, Executive Vice President, BioPharmaceuticals R&D said: “We are excited by the positive results from the Phase III WAYPOINT trial, which show that patients with nasal polyps strongly benefitted from treatment with tezepelumab. These results reinforce that tezepelumab’s first-in-class mode of action, targeting TSLP at the top of the inflammatory cascade, effectively addresses the multiple drivers of epithelial-driven inflammatory diseases.”

The safety profile and tolerability of TEZSPIRE in this trial were consistent with the known profile of the medicine.

Full results will be shared with regulatory authorities and the scientific community at an upcoming medical meeting.

TEZSPIRE is currently approved for the treatment of severe asthma in the US, EU, Japan, and nearly 60 countries across the globe.^2-5 It is approved as a single-use pre-filled syringe and auto-injector for self-administration in the US and EU.^2,3

INDICATIONS AND LIMITATIONS 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 (nasal polyps))

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 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

Epithelial dysfunction and inflammation are important characteristics of chronic rhinosinusitis and impede the ability of the epithelium to act as a physical and immunological barrier against the external environment.¹¹ Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine that has been implicated in shared pathophysiological processes underlying severe asthma and CRSwNP.^10,12

Current treatments for CRSwNP include intranasal and/or systemic corticosteroids, surgery and biologics.^8,13-16

Phase III WAYPOINT trial

WAYPOINT is 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 Participants received tezepelumab or placebo, administered via subcutaneous injection. The trial also included a post-treatment follow-up period of 12-24 weeks for participants who completed the 52-week treatment period.¹

The co-primary endpoints 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 bi-weekly mean nasal congestion, measured by the participant reported Nasal Congestion Score evaluated as part of the daily Nasal Polyposis Symptom Diary.¹ Key secondary endpoints included loss of smell; improvement in disease specific health-related quality of life as measured by SinoNasal Outcome Test (SNOT-22) 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, in the population with co-morbid asthma, pre-bronchodilator FEV1 at Week 52.

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 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 airway inflammation associated with severe asthma, including airway hyperresponsiveness.^17,18 TEZSPIRE is approved in the US, EU, Japan and other countries for the treatment of severe asthma.^19-21

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’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit www.astrazeneca-us.com and follow us on social media @AstraZeneca.

References

1. 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: November 2024].
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5. Data on File. AstraZeneca. 2024. REF-251231.
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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: November 2024].
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. Laidlaw TM, et al. Chronic Rhinosinusitis with nasal polyps and asthma. J Allergy Clin Immunol Pract 2021;9:1133–1141.
11. Wynne M, et al. Contribution of epithelial cell dysfunction to the pathogenesis of chronic rhinosinusitis with nasal polyps. Am J Rhinol Allergy. 2019;33:782–790.
12. Liao B, et al. Interaction of thymic stromal lymphopoietin, IL-33, and their receptors in epithelial cells in eosinophilic chronic rhinosinusitis with nasal polyps. Allergy. 2015;70:1169–1180.
13. 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 November 2024].
14. Xolair (omalizumab) US prescribing information; Available at: https://www.gene.com/download/pdf/xolair_prescribing.pdf [Last accessed: November 2024].
15. Nucala (mepolizumab) US prescribing information; Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761122s006,125526s018lbl.pdf. [Last accessed November 2024].
16. Dupixent (dupilumab) US prescribing information; Available at: https://www.regeneron.com/downloads/dupixent_fpi.pdf. [Last accessed: November 2024].
17. Corren J, et al. Tezepelumab in adults with uncontrolled asthma . N Engl J Med. 2017;377:936-946.
18. Varricchi G, et al. Thymic Stromal Lymphopoietin Isoforms, Inflammatory Disorders, and Cancer. Front Immunol. 2018;9:1595.
19. AstraZeneca plc. Tezspire (tezepelumab) approved in the US for severe asthma. Available at: https://www.astrazeneca.com/media-centre/press-releases/2021/tezspire-tezepelumab-approved-in-the-us-for-severe-asthma.html. [Last accessed: November 2024].
20. AstraZeneca plc. Tezspire approved in the EU for the treatment of severe asthma. 2022. Available at: https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2022/tezspire-approved-in-the-eu-for-the-treatment-of-severe-asthma.html. [Last accessed: November 2024].
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FAQ

What were the results of AZN's TEZSPIRE Phase III WAYPOINT trial?

TEZSPIRE met both co-primary endpoints, showing statistically significant reduction in nasal polyp size and nasal congestion compared to placebo in patients with chronic rhinosinusitis with nasal polyps.

What is the current approval status of TEZSPIRE (AZN)?

TEZSPIRE is currently approved for severe asthma treatment in the US, EU, Japan, and nearly 60 countries globally.

What were the safety findings for TEZSPIRE in the WAYPOINT trial?

The safety profile and tolerability of TEZSPIRE in the WAYPOINT trial were consistent with the known profile of the medicine.

What condition was studied in AZN's WAYPOINT trial for TEZSPIRE?

The WAYPOINT trial studied chronic rhinosinusitis with nasal polyps (CRSwNP) in adult patients who were symptomatic despite standard treatment.