Statistically Significant Reduction in Nasal Polyp Size, Nasal Congestion Compared to Placebo

THOUSAND OAKS, Calif., Nov. 7, 2024 /PRNewswire/ -- Amgen (NASDAQ:AMGN) and AstraZeneca today announced positive top-line results from the Phase 3 WAYPOINT trial in patients with chronic rhinosinusitis with nasal polyps (CRSwNP [nasal polyps]). The trial demonstrated patients treated with TEZSPIRE^®(tezepelumab-ekko) had a statistically significant and clinically meaningful reduction in the size of nasal polyps and reduced nasal congestion compared to placebo. The safety profile and tolerability of TEZSPIRE in the trial were consistent with the known profile of the medicine.

WAYPOINT was a randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of TEZSPIRE administered subcutaneously in adults with severe CRSwNP. Participants in the trial were symptomatic despite treatment with standard of care, intranasal corticosteroids (INCS).¹ CRSwNP is a complex inflammatory condition characterized by persistent inflammation of the nasal mucosa accompanied by soft tissue growths, called nasal polyps, and is most commonly treated with INCS and surgery, if required.^2,3

"Chronic rhinosinusitis with nasal polyps negatively impact patients' daily lives with the obstructions leading to disturbances in smell, taste and sleep, as well as pain and fatigue," said 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. "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."

"The top-line results from our Phase 3 WAYPOINT study represent a significant step forward in our commitment to enhancing the lives of those affected by chronic rhinosinusitis with nasal polyps," said Jay Bradner, M.D., executive vice president of Research and Development and chief scientific officer at Amgen. "The data highlight tezepelumab's unique capacity to target multiple inflammatory pathways by acting directly at the epithelium, resulting in meaningful symptom relief that can improve patients' daily experiences."

"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," said 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. "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."

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

About the Phase 3 WAYPOINT Trial

WAYPOINT is a double-blind, multi-center, 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 pre-bronchodilator FEV1 in patients with comorbid asthma and aspirin-exacerbated respiratory disease/NSAID-exacerbated respiratory disease (NSAID-ERD) at Week 52.¹

About 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.^2,3Nasal 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.^4-6

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.⁷ Estimates suggest that up to 56% of patients with CRSwNP have comorbid asthma. Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine that has been implicated in shared pathophysiological processes underlying severe asthma and CRSwNP.^6,8

Current treatments for CRSwNP include intranasal and/or systemic corticosteroids, surgery and biologic medication.^4,9-12

About TEZSPIRE^® (tezepelumab-ekko)

TEZSPIRE 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, TEZSPIRE targets and blocks 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.^13,14TSLP is released in response to multiple triggers associated with asthma exacerbations, including allergens, viruses and other airborne particles.

Expression of TSLP is increased in the airways of patients with asthma and has been correlated with disease severity.^6,16Blocking TSLP may prevent the release of pro-inflammatory cytokines by immune cells, resulting in the prevention of asthma exacerbations and improved asthma control.^14-16 By working at the top of the cascade, TEZSPIRE helps stop inflammation at the source and has the potential to treat a broad population of severe asthma patients.^16-18

TEZSPIRE is currently approved for the treatment of severe asthma in the US, EU, Japan, and more than 50 countries across the globe.^19-22 It is approved as a pre-filled, single-use pen and auto-injector for self-administration in the US and EU.^19,20

Beyond severe asthma and CRSwNP, TEZSPIRE is also in development for other potential indications including chronic obstructive pulmonary disease (COPD) and eosinophilic esophagitis (EoE).^{23, 24} In October 2021, tezepelumab was granted Orphan Drug Designation by the 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.

About the Amgen and AstraZeneca Collaboration

In 2020, Amgen and AstraZeneca updated the 2012 collaboration agreement for TEZSPIRE. Both companies will continue to share costs and profits equally after payment by AstraZeneca of a mid-single-digit 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 U.S., with AstraZeneca recording its share of U.S. profits as Collaboration Revenue. Outside of the U.S., AstraZeneca will record product sales, with Amgen recording profit share as Other/Collaboration revenue.

TEZSPIRE^® (tezepelumab-ekko) U.S. 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.

TEZSPIRE^® (tezepelumab-ekko) Important Safety Information

CONTRAINDICATIONS

Known hypersensitivity to tezepelumab-ekko or excipients.

WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions

Hypersensitivity reactions were observed in the clinical trials (e.g., 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 (i.e., 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 the full Prescribing Information including Patient Information and Instructions for Use.

You may report side effects related to AstraZeneca products by clicking here.

About Amgen

Amgen discovers, develops, manufactures and delivers innovative medicines to help millions of patients in their fight against some of the world's toughest diseases. More than 40 years ago, Amgen helped to establish the biotechnology industry and remains on the cutting-edge of innovation, using technology and human genetic data to push beyond what's known today. Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases.

In 2024, Amgen was named one of the "World's Most Innovative Companies" by Fast Company and one of "America's Best Large Employers" by Forbes, among other external recognitions. Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average^®, and it is also part of the Nasdaq-100 Index^®, which includes the largest and most innovative non-financial companies listed on the Nasdaq Stock Market based on market capitalization.

For more information, visit Amgen.com and follow Amgen on X, LinkedIn, Instagram, TikTok, YouTube and Threads.

Amgen Forward-Looking Statements

This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including any statements on the outcome, benefits and synergies of collaborations, or potential collaborations, with any other company (including BeiGene, Ltd. or Kyowa Kirin Co., Ltd.), the performance of Otezla^®(apremilast) (including anticipated Otezla sales growth and the timing of non-GAAP EPS accretion), Amgen's acquisitions of Teneobio, Inc., ChemoCentryx, Inc., or Horizon Therapeutics plc (including the prospective performance and outlook of Horizon's business, performance and opportunities, any potential strategic benefits, synergies or opportunities expected as a result of such acquisition, and any projected impacts from the Horizon acquisition on Amgen's acquisition-related expenses going forward), as well as estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes, effects of pandemics or other widespread health problems on Amgen's business, outcomes, progress, and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission reports filed by Amgen, including its most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Unless otherwise noted, Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.

No forward-looking statement can be guaranteed and actual results may differ materially from those Amgen projects. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for Amgen to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and Amgen expects similar variability in the future. Even when clinical trials are successful, regulatory authorities may question the sufficiency for approval of the trial endpoints Amgen has selected. Amgen develops product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as Amgen may have believed at the time of entering into such relationship. Also, Amgen or others could identify safety, side effects or manufacturing problems with its products, including its devices, after they are on the market.

Amgen's results may be affected by its ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments involving current and future products, sales growth of recently launched products, competition from other products including biosimilars, difficulties or delays in manufacturing its products and global economic conditions. In addition, sales of Amgen's products are affected by pricing pressure, political and public scrutiny and reimbursement policies imposed by third-party payers, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment. Furthermore, Amgen's research, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and foreign government regulatory authorities. Amgen's business may be impacted by government investigations, litigation and product liability claims. In addition, Amgen's business may be impacted by the adoption of new tax legislation or exposure to additional tax liabilities. If Amgen fails to meet the compliance obligations in the corporate integrity agreement between Amgen and the U.S. government, Amgen could become subject to significant sanctions. Further, while Amgen routinely obtains patents for its products and technology, the protection offered by its patents and patent applications may be challenged, invalidated or circumvented by its competitors, or Amgen may fail to prevail in present and future intellectual property litigation. Amgen performs a substantial amount of its commercial manufacturing activities at a few key facilities, including in Puerto Rico, and also depends on third parties for a portion of its manufacturing activities, and limits on supply may constrain sales of certain of its current products and product candidate development. An outbreak of disease or similar public health threat, such as COVID-19, and the public and governmental effort to mitigate against the spread of such disease, could have a significant adverse effect on the supply of materials for Amgen's manufacturing activities, the distribution of Amgen's products, the commercialization of Amgen's product candidates, and Amgen's clinical trial operations, and any such events may have a material adverse effect on Amgen's product development, product sales, business and results of operations. Amgen relies on collaborations with third parties for the development of some of its product candidates and for the commercialization and sales of some of its commercial products. In addition, Amgen competes with other companies with respect to many of its marketed products as well as for the discovery and development of new products. Further, some raw materials, medical devices and component parts for Amgen's products are supplied by sole third-party suppliers. Certain of Amgen's distributors, customers and payers have substantial purchasing leverage in their dealings with Amgen. The discovery of significant problems with a product similar to one of Amgen's products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on its business and results of operations. Amgen's efforts to collaborate with or acquire other companies, products or technology, and to integrate the operations of companies or to support the products or technology Amgen has acquired, may not be successful. There can be no guarantee that Amgen will be able to realize any of the strategic benefits, synergies or opportunities arising from the Horizon acquisition, and such benefits, synergies or opportunities may take longer to realize than expected. Amgen may not be able to successfully integrate Horizon, and such integration may take longer, be more difficult or cost more than expected. A breakdown, cyberattack or information security breach of Amgen's information technology systems could compromise the confidentiality, integrity and availability of Amgen's systems and Amgen's data. Amgen's stock price may be volatile and may be affected by a number of events. Amgen's business and operations may be negatively affected by the failure, or perceived failure, of achieving its environmental, social and governance objectives. The effects of global climate change and related natural disasters could negatively affect Amgen's business and operations. Global economic conditions may magnify certain risks that affect Amgen's business. Amgen's business performance could affect or limit the ability of the Amgen Board of Directors to declare a dividend or its ability to pay a dividend or repurchase its common stock. Amgen may not be able to access the capital and credit markets on terms that are favorable to it, or at all.

Any scientific information discussed in this news release relating to new indications for Amgen's products is preliminary and investigative and is not part of the labeling approved by the U.S. Food and Drug Administration for the products. The products are not approved for the investigational use(s) discussed in this news release, and no conclusions can or should be drawn regarding the safety or effectiveness of the products for these uses.

CONTACT: Amgen, Thousand Oaks

Kate Meyer, 872-867-0754 (media)

Elissa Snook, 609-251-1407 (media)

Justin Claeys, 805-313-9775 (investors)

References:

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].
Bachert C, et al. Phenotypes and Emerging Endotypes of Chronic Rhinosinusitis. J Allergy Clin Immunol Pract. 2016; 4 (4): 621-628.
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].
Stevens WW, et al. Chronic Rhinosinusitis with Nasal Polyps. J Allergy Clin Immunol Pract. 2016; 4 (4): 565-572. 
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. 
Laidlaw TM, et al. Chronic Rhinosinusitis with nasal polyps and asthma.  J Allergy Clin Immunol Pract 2021;9:1133–1141.
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.
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.
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].
Xolair (omalizumab) US prescribing information; Available at: https://www.gene.com/download/pdf/xolair_prescribing.pdf [Last accessed: November 2024].
Nucala (mepolizumab) US prescribing information; Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761122s006,125526s018lbl.pdf. [Last accessed November 2024].
Dupixent (dupilumab) US prescribing information; Available at: https://www.regeneron.com/downloads/dupixent_fpi.pdf. [Last accessed: November 2024].
Menzies-Gow A, et al. Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma. N Engl J Med. 2021;384:1800-1809. DOI: 10.1056/NEJMoa2034975.
Varricchi G, et al. Thymic Stromal Lymphopoietin Isoforms, Inflammatory Disorders, and Cancer. Front Immunol. 2018; 9: 1595.
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.
Corren J, et al. Tezepelumab in adults with uncontrolled asthma . N Engl J Med. 2017;377:936-946.
Menzies-Gow A, et al. Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma. N Engl J Med. 2021;384:1800-1809.
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.
Tezspire (tezepelumab) US prescribing information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761224s003lbl.pdf. [Last accessed: November 2024].
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: November 2024].
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: November 2024].
Data on File. AstraZeneca. 2024. REF-251231.
Clinicaltrials.gov. Tezepelumab COPD Exacerbation Study (COURSE) [Online]. Available at: https://clinicaltrials.gov/ct2/show/NCT04039113. [Last accessed: November 2024].
Clinicaltrials.gov. Efficacy and Safety of Tezepelumab in Patients with Eosinophilic Esophagitis (CROSSING). Available at: https://clinicaltrials.gov/study/NCT05583227?rank=1. [Last accessed: November 2024].

View original content to download multimedia:https://www.prnewswire.com/news-releases/tezspire-met-both-co-primary-endpoints-in-phase-3-trial-for-chronic-rhinosinusitis-with-nasal-polyps-302299720.html

SOURCE Amgen

TEZSPIRE MET BOTH CO-PRIMARY ENDPOINTS IN PHASE 3 TRIAL FOR CHRONIC RHINOSINUSITIS WITH NASAL POLYPS