Press Release Details

THOUSAND OAKS, Calif., Feb. 26, 2021 /PRNewswire/ -- Amgen (NASDAQ:AMGN) and AstraZeneca today announced positive full results from the pivotal NAVIGATOR Phase 3 trial, which showed the potential of tezepelumab to be a first-in-class medicine in severe asthma. When added to standard of care (SoC), tezepelumab demonstrated a statistically significant and clinically meaningful reduction in the annualized asthma exacerbation rate (AAER) in patients with severe, uncontrolled asthma, compared to placebo.¹ The results were presented at the American Academy of Asthma Allergy & Immunology Annual Meeting. NAVIGATOR is a pivotal Phase 3 trial that will form the basis of regulatory filing.

Tezepelumab, a potential first-in-class medicine, when added to standard of care (SoC) achieved a 56% reduction (p<0.001) in AAER over 52 weeks in the overall patient population, compared to placebo when added to SoC.² Tezepelumab is the only biologic to consistently and significantly reduce AAER in a broad population of severe asthma patients irrespective of the baseline eosinophil counts across Phase 2 and Phase 3 clinical trials.^2-10

"We believe the full results of the NAVIGATOR trial are a breakthrough for the millions of people living with severe asthma," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "The reduction in exacerbation rates tezepelumab demonstrated, regardless of eosinophil or allergic status, is impressive. We are thrilled with these results and what they could mean for patients suffering with severe asthma."

In a pre-specified analysis of the subgroup of patients with baseline eosinophil counts less than 300 cells per microliter, tezepelumab achieved a statistically significant and clinically meaningful 41% reduction (p<0.001) in AAER.² Importantly, clinically meaningful reductions in AAER were also observed in two additional subgroups: a 39% reduction in patients with baseline eosinophil counts less than 150 cells per microliter and a 70% reduction in patients with greater than or equal to 300 cells per microliter.²

Additionally, clinically meaningful reductions in AAER compared to placebo were observed in the tezepelumab-treated patients irrespective of allergy status and fractional exhaled nitric oxide (FeNO) level, biomarkers used by clinicians to inform treatment options.²

"These are ground-breaking results for the many patients with severe asthma who continue to face debilitating symptoms despite receiving standard of care inhaled medicines and currently approved biologics," said Professor Andrew Menzies-Gow, director of the Lung Division, Royal Brompton Hospital, London, UK, and principal investigator of the NAVIGATOR Phase 3 trial. "Tezepelumab has the potential to transform treatment for a broad population of patients with severe asthma regardless of their type of inflammation, including those with and without an eosinophilic phenotype."   

Tezepelumab also demonstrated statistically significant improvements in every key secondary endpoint compared to placebo, including lung function measurements, asthma control, and health-related quality of life.²

There were no clinically meaningful differences in safety results between the tezepelumab and placebo groups. The most frequently reported adverse events were nasopharyngitis, upper respiratory tract infection and headache.²

Tezepelumab blocks the action of thymic stromal lymphopoietin (TSLP), an epithelial cytokine that plays a key role across the spectrum of asthma inflammation.^3,10 NAVIGATOR is the first Phase 3 trial to show benefit in severe asthma by targeting TSLP.²

The statistically significant and clinically meaningful exacerbation rate reductions demonstrated with tezepelumab in patients with baseline eosinophil counts less than 300 cells per microliter support the U.S. Food and Drug Administration Breakthrough Therapy Designation granted to tezepelumab in September 2018 for patients with severe asthma, without an eosinophilic phenotype.^2-3 Tezepelumab is being developed by AstraZeneca in collaboration with Amgen (see AstraZeneca and Amgen collaboration below).

About Severe Asthma
Asthma is a complex and heterogeneous disease affecting an estimated 339 million people worldwide.^11,12 Approximately 10% of asthma patients have severe asthma.^11,12 Globally, there are approximately 2.5 million severe asthma patients who are uncontrolled or biologic eligible, with approximately 1 million in the U.S. Many severe asthma patients have an inadequate response to currently available biologics and oral corticosteroids and thus fail to achieve asthma control.^11-13 Severe, uncontrolled asthma is debilitating with patients experiencing frequent exacerbations, significant limitations on lung function and a reduced quality of life.^11-13 Patients with severe asthma have twice the risk of asthma-related hospitalizations.^14,15 There is also a significant socio-economic burden, with these patients accounting for 50% of asthma-related costs.¹⁶

Multiple inflammatory pathways are involved in the pathogenesis of asthma.^17,18,19 Eosinophilic asthma, and more broadly, T2 inflammation-driven asthma, accounts for about two-thirds of patients with severe asthma.¹⁹ These patients are typically characterized as having elevated levels of inflammatory biomarkers, including blood eosinophils, serum IgE and fractional exhaled nitric oxide (FeNO).^20,21 However, many patients do not fit the criteria for eosinophilic or allergic asthma, may have unclear or multiple drivers of inflammation, and may not qualify for or respond well to a current biologic medicine.²¹

NAVIGATOR and the PATHFINDER Clinical Trial Program
Building on the positive Phase 2b PATHWAY trial, the Phase 3 PATHFINDER program included two trials, NAVIGATOR and SOURCE.^22-25 The program includes additional planned mechanistic and long-term safety trials.

NAVIGATOR is a Phase 3, randomized, double-blinded, placebo-controlled trial in 1,061 adults (18–80 years old) and adolescents (12–17 years old) with severe, uncontrolled asthma, who were receiving treatment with medium- or high-dose ICS plus at least one additional controller medication with or without OCS. NAVIGATOR met the primary endpoint with tezepelumab added to SoC demonstrating a statistically significant and clinically meaningful reduction in the AAER over 52 weeks in the overall patient population, compared to placebo added to SoC. The trial also met the primary endpoint in the subgroup of patients with baseline eosinophil counts less than 300 cells per microliter, with tezepelumab demonstrating a statistically significant and clinically meaningful reduction in AAER in that patient population. Similar reductions in AAER were observed in the subgroup of patients with baseline eosinophil counts less than 150 cells per microliter.²⁵

SOURCE is a Phase 3 multicenter, randomized, double-blinded, parallel-group, placebo-controlled trial for 48 weeks in adult patients with severe asthma who require continuous treatment with ICS plus long-acting beta2-agonists (LABA), and chronic treatment with maintenance OCS therapy.²³  In the trial, patients were randomized to receive tezepelumab 210 mg every four weeks or placebo as add-on therapy, with patients maintained on their currently prescribed ICS plus LABA, with or without other asthma controller therapy.²³

Patients who participated in the NAVIGATOR and SOURCE trials were eligible to continue in DESTINATION, a Phase 3 extension trial assessing long term safety and efficacy.²⁶

About Tezepelumab
Tezepelumab is an investigational, potential 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, tezepelumab targets and blocks thymic stromal lymphopoietin (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.^3,9,22

TSLP is released in response to multiple triggers associated with asthma exacerbations, including allergens, viruses and other airborne particles. ^3,9 Expression of TSLP is increased in the airways of patients with asthma and has been correlated with disease severity.^3,22 Blocking TSLP may prevent the release of pro-inflammatory cytokines by immune cells, resulting in the prevention of asthma exacerbations and improved asthma control. ^3,22 By working at the top of the cascade, tezepelumab helps stop inflammation at the source and has the potential to treat a broad population of severe asthma patients.^3,22

Amgen and AstraZeneca Collaboration
In 2020, Amgen and AstraZeneca updated the 2012 collaboration agreement for tezepelumab. 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 in North America, Amgen and AstraZeneca will jointly commercialize tezepelumab. Amgen will record sales in the U.S. and AstraZeneca will record sales in Canada. Outside the U.S., Amgen will record sales as collaboration revenue.

Amgen Inflammation
Amgen brings therapies to millions of people with inflammatory diseases, with a focus on serving unmet patient needs. For those with debilitating moderate to severe rheumatoid arthritis, psoriatic arthritis, moderate to severe plaque psoriasis, ankylosing spondylitis, asthma, and other chronic conditions, the suffering and needs are severe. Complex diseases of inflammation have defied simple solutions, and the breadth of inflammatory disease and the burden patients bear is not well understood.

For more than two decades, Amgen has been committed to advancing the science and the understanding around inflammation to address the unmet patient needs that exist and expanding our portfolio. We lead with science through discovery research that is disease-agnostic and biology-first, modality-second. In doing so, we have introduced and evolved novel therapies that have changed the lives of patients.

Our commitment to patients is reflected not only in where we have succeeded, but in where we have failed and opened new doors. Throughout, we have remained dedicated to the principle of leading with science, pursuing where pathways and promising discoveries in inflammation take us, and not relenting until innovative solutions for patients are found. It's a commitment that extends beyond introducing novel therapies. We are focused on improving the entire patient journey.

About Amgen 

Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.  

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.  

For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.  

Amgen Forward-Looking Statements
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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.

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CONTACT: Amgen, Thousand Oaks 
Megan Fox, 805-447-1423 (media)
Trish Rowland, 805-447-5631(media) 
Arvind Sood, 805-447-1060 (investors) 

References

1. Bonini M, Di Paolo M, Bagnasco D, et al. Minimal clinically important difference for asthma endpoints: an expert consensus report. Eur Respir Rev. 2020; 29: 190137.
2. Menzies-Gow A, Corre J, Bourdin A, et al. Efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma: results from the phase 3 NAVIGATOR study. L 46. AAAAI poster. February 2021. 
3. Corren J, Parnes JR, Wang L, et al. Tezepelumab in Adults with Uncontrolled Asthma [published correction appears in N Engl J Med. 2019 May 23; 380 (21): 2082]. N Engl J Med. 2017; 377 (10): 936-946.
4. Wenzel S, Castro M, Corren J, et al. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet. 2016;388 (10039): 31-44.
5. Castro M, Corren J, Pavord I.D, et al. Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma. N Engl J Med 2018; 378:2486-2496.
6. Bleecker ER, FitzGerald JM, Chanez P, et al, on behalf of the SIROCCO study investigators. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting beta2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet 2016: 388 (10056): 2115-2127.
7. 7.  FitzGerald JM, Bleecker ER, Nair P, et al, on behalf of the CALIMA study investigators. Benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2016: 388(10056): 2128-2141.
8. FitzGerald JM, Bleecker ER, Menzies-Gow A, et al. Predictors of enhanced response with benralizumab for patients with severe asthma: pooled analysis of the SIROCCO and CALIMA studies. Lancet Respir Med. 2018; 6 (1): 51-64.
9. Varricchi G, Pecoraro A, Marone G, et al. Thymic Stromal Lymphopoietin Isoforms, Inflammatory Disorders, and Cancer. Front Immunol. 2018; 9: 1595.
10. Ortega HG, Liu MC, Pavord ID, et al; on behalf of the MENSA Investigators. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014;371(13):1198-207.
11. Kupczyk M, Wenzel S. U.S. and European severe asthma cohorts: what can they teach us about severe asthma? J Intern Med 2012;272:121–32.
12. Wenzel S. Severe Asthma in Adults. Am J Respir Crit Care Med. 2005; 172; 149–60.
13. Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014; 43: 343–73.
14. Price D, Fletcher M, van der Molen T. Asthma control and management in 8,000 European patients: the REcognise Asthma and LInk to Symptoms and Experience (REALISE) survey. NPJ Prim Care Respir Med. 2014; 12; 24: 14009.
15. World Allergy Organization (WAO). The management of severe asthma: economic analysis of the cost of treatments for severe asthma. Available at: https://www.worldallergy.org/educational_programs/world_allergy_forum/anaheim2005/blaiss.php [Last accessed: February 2021].
16. Busse WW. Biological Treatments for Severe Asthma: A Major Advance in Asthma Care. Allergol Int 2019; 68: 158–66.
17. Godar M, Blanchetot C, de Haard H, et al. Personalized medicine with biologics for severe type 2 asthma: current status and future prospects. MAbs. 2018; 10 (1): 34–45.
18. Rabe KF, Busse W, Pavord I, Castro M. Raising the clinical bar beyond current biologics in uncontrolled persistent asthma: translating emerging data in future clinical decisions. EMJ Allergy Immunol. 2018; 3: 60-9.
19. Peters MC, Mekonnen ZK, Yuan S, et al. Measures of gene expression in sputum cells can identify TH2-high and TH2-low subtypes of asthma. J Allergy Clin Immunol. 2014; 133: 388–94.
20. Clinicaltrials.gov. Study to Evaluate the Efficacy and Safety of Tezepelumab in Reducing Oral Corticosteroid Use in Adults With Oral Corticosteroid Dependent Asthma (SOURCE) [Online]. Available at: https://clinicaltrials.gov/ct2/show/NCT03406078. [Last accessed: February 2021].
21. Fahy JV. Type 2 inflammation in asthma--present in most, absent in many. Nat Rev Immunol. 2015; 15: 57-65.
22. Roseti S, Corren J, Parnes JR, et al. Efficacy and safety of tezepelumab in adults with severe asthma: A randomized phase 2 study. European Respiratory Journal 2017; 50: OA3189.
23. Wechsler, M.E., Colice, G., Griffiths, J.M. et al. SOURCE: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel group trial to evaluate the efficacy and safety of tezepelumab in reducing oral corticosteroid use in adults with oral corticosteroid dependent asthma. Respir Res 2020; 21: 264.
24. Clinicaltrials.gov. Study to Evaluate Tezepelumab in Adults & Adolescents With Severe Uncontrolled Asthma (NAVIGATOR) [Online]. Available at: https://clinicaltrials.gov/ct2/show/NCT03347279. [Last accessed: February 2021].
25. AstraZeneca plc. Tezepelumab NAVIGATOR Phase III trial met primary endpoint of a statistically significant and clinically meaningful reduction in exacerbations in a broad population of patients with severe asthma. Available at: https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/tezepelumab-navigator-phase-iii-trial-met-primary-endpoint.html. [Last accessed: February 2021].
26. Clinicaltrials.gov. Extension Study to Evaluate the Safety and Tolerability of Tezepelumab in Adults and Adolescents With Severe, Uncontrolled Asthma (DESTINATION) [Online]. Available at: https://clinicaltrials.gov/ct2/show/NCT03706079. [Last accessed: February 2021].

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