Press Release Details

THOUSAND OAKS, Calif., Sept. 6, 2017 /PRNewswire/ -- Amgen (NASDAQ:AMGN) and AstraZeneca (NYSE:AZN) today announced results from the PATHWAY Phase 2b trial of tezepelumab that showed a significant reduction in the annual asthma exacerbation rate compared with placebo in patients with severe, uncontrolled asthma. Tezepelumab is a novel anti-thymic stromal lymphopoietin (TSLP) monoclonal antibody being developed by MedImmune, AstraZeneca's global biologics research and development arm, in collaboration with Amgen.

The trial results were published today in the New England Journal of Medicine (NEJM), and will be followed by an oral presentation at the European Respiratory Society (ERS) International Congress 2017 in Milan on Sept. 12, 2017.¹

The PATHWAY trial achieved its primary efficacy endpoint, showing annual asthma exacerbation rate reductions of 61 percent, 71 percent and 66 percent in the tezepelumab arms receiving either 70 mg or 210 mg every four weeks or 280 mg every two weeks, respectively (p<0.001 for all comparisons to placebo). In the trial, tezepelumab was given as an add-on therapy to patients with a history of asthma exacerbations and uncontrolled asthma despite receiving inhaled corticosteroids/long-acting beta-agonists with or without oral corticosteroids (OCS) and additional asthma controllers.²

Significant and clinically meaningful reductions in the exacerbation rate were observed independent of baseline blood eosinophil count or other type 2 [(T2) referred to as Th2 in the NEJM publication] inflammatory biomarkers. Tezepelumab also demonstrated improvements in lung function at all doses and in asthma control at the two higher doses (p<0.05 for all comparisons to placebo). The incidence of adverse events was similar between the tezepelumab and placebo groups. The most common adverse events (≥5 percent) in tezepelumab-treated patients were asthma, nasopharyngitis, headaches and bronchitis.² Future studies in large populations of patients will be important in confirming the results demonstrated in this trial.

"These efficacy results confirm the hypothesis that TSLP is an important mediator of inflammation in severe asthma," said Jonathan Corren, M.D., David Geffen School of Medicine, UCLA and Principal Investigator of the PATHWAY trial. "Due to its activity early in the inflammatory cascade, tezepelumab may be suitable for patients with both T2 and non-T2 driven asthma, including those ineligible for current biologic therapies which only target the T2 pathway."

"The responses seen with tezepelumab in the PATHWAY trial show promise for a novel therapeutic option with the potential to impact multiple downstream inflammatory pathways associated with asthma," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "We are committed to leveraging our deep understanding of inflammatory pathways to develop innovative treatments that address significant unmet medical needs."

TSLP is an upstream epithelial cytokine that drives multiple inflammatory pathways in various diseases, including asthma. TSLP is active in the regulation of T2 immunity; however, it may also play a role in non-T2 driven inflammation by activating or signaling to many types of cells, such as mast cells, basophils, natural killer T cells, innate lymphoid cells and neutrophils.^3-7 Therefore, TSLP has been identified as a potential therapeutic target across a broad asthma population.^3,7

About Severe Asthma
Asthma affects 315 million individuals worldwide,⁸ and up to 10 percent of asthma patients have severe asthma, which may be uncontrolled despite high doses of standard of care asthma controller medicines and can require the use of chronic OCS.^9,10

Severe, uncontrolled asthma is debilitating, with patients experiencing frequent exacerbations and significant limitations on lung function.^11,12

There is a significant physical and socio-economic burden of severe, uncontrolled asthma with these patients accounting for 50 percent of asthma-related costs.¹³

T2 inflammation-driven (T2 high) asthma is present in more than two-thirds of patients with severe asthma and is typically characterized by elevated levels of T2 inflammatory biomarkers, including blood eosinophils, serum IgE and fractional exhaled nitric oxide (FeNO).^14,15 Conversely, approximately one-third of patients with severe asthma do not present with features of an activated T2 inflammatory pathway, and no biologic treatment options currently exist for these patients whose non-T2 driven disease is uncontrolled on established standard of care therapies.¹⁶

About Tezepelumab
Tezepelumab is the first of a new kind of potential medicines targeting TSLP.⁷ Tezepelumab is a human anti-TSLP monoclonal antibody that is designed to specifically bind to human TSLP and prevent interaction with its receptor complex.⁷ Blocking TSLP with tezepelumab may prevent the release of pro-inflammatory cytokines by immune cells targeted by TSLP. Due to its activity early in the inflammation cascade, tezepelumab may be suitable for a broad population of patients with severe, uncontrolled asthma, including in those whose asthma is not T2 driven.

About the PATHWAY Trial
The PATHWAY trial was a Phase 2b 52-week, randomized, double-blind, parallel group, placebo-controlled trial designed to evaluate the efficacy and safety of three dose regimens of tezepelumab, 70 mg and 210 mg every four weeks and 280 mg every two weeks, as an add-on therapy in patients with a history of asthma exacerbations and uncontrolled asthma receiving inhaled corticosteroids/long-acting beta-agonists with or without OCS and additional asthma controllers.¹⁷

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.

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 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 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 it 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 manufacturing facilities 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. 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 acquire other companies or products and to integrate the operations of companies Amgen has acquired may not be successful. Amgen may not be able to access the capital and credit markets on terms that are favorable to it, or at all. Amgen is increasingly dependent on information technology systems, infrastructure and data security. Amgen's stock price may be volatile and may be affected by a number of events. 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.

The scientific information discussed in this news release related to Amgen's product candidates is preliminary and investigative. Such product candidates are not approved by the U.S. Food and Drug Administration, and no conclusions can or should be drawn regarding the safety or effectiveness of the product candidates.

CONTACT: Amgen, Thousand Oaks
Kristen Davis, 805-447-3008 (media)
Kristen Neese, 805-313-8267 (media)
Arvind Sood, 805-447-1060 (investors)

References

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2. Corren J, Parnes JR, Wang L, et al. Tezepelumab in Adults with Uncontrolled Asthma. New Engl J Med 2017;377:936-46.
3. West EE, Kashyap M, Leonard WJ. TSLP: a key regulator of asthma pathogenesis. Drug Discov Today Dis Mech 2012;9:e38–e88.
4. Lee HC, Headley MB, Loo YM, et al. Thymic stromal lymphopoietin is induced by respiratory syncytial virus-infected airway epithelial cells and promotes a type 2 response to infection. J Allergy Clin Immunol 2012;130:1187–96.
5. Nagata Y, Kamijuku H, Taniguchi M, et al. Differential role of thymic stromal lymphopoietin in the induction of airway hyperreactivity and Th2 immune response in antigen-induced asthma with respect to natural killer T cell function. Int Arch Allergy Immunol 2007;144:305–14.
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13. World Allergy Organization. The management of severe asthma: economic analysis of the cost of treatments for severe asthma. 2013. 1 August 2017. Available at: http://www.worldallergy.org/educational_programs/world_allergy_forum/anaheim2005/blaiss.php. Accessed August 31, 2017.
14. Fahy JV. Type 2 inflammation in asthma--present in most, absent in many. Nat Rev Immunol 2015;15:57–65.
15. Shaw DE, Sousa AR, Fowler SJ, et al. Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort. Eur Respir J 2015;46:1308–21.
16. Fajt ML, Wenzel SE. Development of new therapies for severe asthma. Allergy Asthma Immunol Res 2017;9:3–14
17. ClinicalTrials.gov Available at: https://clinicaltrials.gov/ct2/show/NCT02054130. Accessed August 31, 2017.

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SOURCE Amgen