FDA APPROVES TEZSPIRE IN THE U.S. FOR SEVERE ASTHMA

- Amgen (NASDAQ:AMGN) today announced that the U.S. Food and Drug Administration (FDA) has approved Amgen and AstraZeneca's Tezspire ™ (tezepelumab-ekko) for the add-on maintenance treatment of adult and pediatric patients aged 12 years and older with severe asthma. 1

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Tezspire was approved following a Priority Review by the FDA and based on results from the PATHFINDER clinical trial program. The application included results from the pivotal NAVIGATOR Phase 3 trial in which Tezspire demonstrated superiority across every primary and key secondary endpoint in patients with severe asthma, compared to placebo, when added to standard therapy. ²

"Today's approval by the FDA marks the first time patients and their physicians will have a biologic option for severe asthma without phenotypic limitations and irrespective of biomarker levels," said David M. Reese , M.D., executive vice president of Research and Development at Amgen. "Asthma is a complex and chronic inflammatory disease that affects everyone differently. By working at the top of the inflammation cascade, Tezspire helps stop the inflammation that causes asthma attacks at the source and has the potential to treat a broad population of people with severe asthma, including those who have historically lacked effective treatment options."

Tezspire is a first-in-class biologic for severe asthma that acts at the top of the inflammatory cascade by targeting thymic stromal lymphopoietin (TSLP), an epithelial cytokine. ³ It is the first and only biologic to consistently and significantly reduce asthma exacerbations across Phase 2 and 3 clinical trials, which included a broad population of severe asthma patients irrespective of key biomarkers, including blood eosinophil counts, allergic status and fractional exhaled nitric oxide (FeNO). ^2,3 Tezspire is the first and only biologic for severe asthma that does not have a phenotype—eosinophilic or allergic—or biomarker limitation within its approved label. ^4-11

"Due to the complex and heterogeneous nature of severe asthma and despite recent advances, many patients continue to experience frequent exacerbations, an increased risk of hospitalization and a significantly reduced quality of life," said Professor Andrew Menzies-Gow , director of the Lung Division, Royal Brompton Hospital, London, UK , and the principal investigator of the NAVIGATOR trial. " Tezspire represents a much-needed new treatment for the many patients who remain underserved and continue to struggle with severe, uncontrolled asthma."

"Severe asthma continues to have a debilitating impact on many of the 34 million people living with the disease worldwide, affecting their breathing and limiting aspects of day-to-day life. The approval of Tezspire is long-awaited positive news for the asthma community," said Tonya Winders , president and chief executive officer at the Allergy & Asthma Network (AAN) and president of the Global Allergy and Airways Patient Platform (GAAPP). "For the first time, many people living with severe asthma have the opportunity to receive treatment regardless of the cause of their inflammation."

Results from the NAVIGATOR Phase 3 trial were published in The New England Journal of Medicine in May 2021 . ² In clinical studies of Tezspire , the most common adverse reactions were nasopharyngitis, upper respiratory tract infection and headache. ²

Tezspire is under regulatory review in the EU, Japan and several other countries around the world.

Commitment to Patient Support
Amgen and AstraZeneca are committed to providing appropriate patients who are prescribed Tezspire with affordable access to the medicine. Patients, caregivers and physicians who need support or resources can contact the Tezspire Together program starting on Monday, Dec. 20 at 8:00 a.m. ET by calling 1-888-TZSPIRE (1-888-897-7473).

Tezspire   ™ (tezepelumab-ekko) U.S. Indication
Tezspire is a first-in-class medicine 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 (e.g., rash and allergic conjunctivitis) can occur following administration of TEZSPIRE. 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, initiate appropriate treatment as clinically indicated and then 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 Tezspire full Prescribing Information .

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

About the NAVIGATOR and the PATHFINDER Clinical Trial Program
In addition to the Phase 2b PATHWAY trial, the Phase 3 PATHFINDER program included two trials, NAVIGATOR and SOURCE. ^2,12-14 The program includes additional mechanistic and long-term safety trials. ¹⁵

NAVIGATOR is a Phase 3, randomized, double-blinded, placebo-controlled trial in adults (18–80 years old) and adolescents (12–17 years old) with severe, uncontrolled asthma, who were receiving standard of care (SoC). SoC was treatment with medium- or high-dose inhaled corticosteroids (ICS) plus at least one additional controller medication with or without daily oral corticosteroid treatment. The trial population included approximately equal proportions of patients with high (≥300 cells per microliter) and low ( 2

The primary efficacy endpoint was the AAER during the 52-week treatment period. Key secondary endpoints included the effect of Tezspire on lung function, asthma control and health-related quality of life. ³

As part of prespecified analyses, the AAER over 52 weeks was also assessed in patients grouped by baseline blood eosinophil count, FeNO level and serum specific immunoglobin E (IgE) status (perennial aeroallergen sensitivity positive or negative). ³ These are inflammatory biomarkers used by clinicians to inform treatment options and involve tests analyzing a patient's blood (eosinophils/IgE) and exhaled air (FeNO).

The most frequently reported adverse events for Tezspire were nasopharyngitis, upper respiratory tract infection and headache. ²

NAVIGATOR is the first Phase 3 trial to show benefit in severe asthma irrespective of eosinophils by targeting TSLP. ² These results support the U.S. Food and Drug Administration Breakthrough Therapy Designation granted to Tezspire in September 2018 for patients with severe asthma, without an eosinophilic phenotype. In July 2021 , Tezspire was the first and only biologic to be granted Priority Review in the U.S. for the treatment of asthma by the FDA.

Patients who participated in our Phase 3 clinical trials were eligible to continue in DESTINATION, a Phase 3 extension trial assessing long-term safety and efficacy. ¹⁶

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. ^3,17 TSLP is released in response to multiple triggers associated with asthma exacerbations, including allergens, viruses and other airborne particles. ^3,17 Expression of TSLP is increased in the airways of patients with asthma and has been correlated with disease severity. ^3,18 Blocking TSLP may prevent the release of pro-inflammatory cytokines by immune cells, resulting in the prevention of asthma exacerbations and improved asthma control. ^3,18 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. ^3,18

Tezspire is also in development for other potential indications including chronic obstructive pulmonary disease, chronic rhinosinusitis with nasal polyps, chronic spontaneous urticaria and eosinophilic esophagitis (EoE). In October 2021 , tezepelumab was granted Orphan Drug Designation by the FDA for the treatment of EoE.

About Severe Asthma
Globally, there are approximately 2.5 million patients with severe asthma who are uncontrolled or biologic eligible, with approximately 1 million in the U.S. Many patients with severe asthma have an inadequate response to currently available biologics and oral corticosteroids and thus fail to achieve asthma control. ^19-24 Uncontrolled asthma occurs when symptoms persist despite treatment. Severe, uncontrolled asthma is debilitating with patients experiencing frequent exacerbations, significant limitations on lung function and a reduced quality of life. ^20-22 Patients with severe uncontrolled asthma have twice the risk of asthma-related hospitalizations. ^25,26 There is also a significant socio-economic burden with these severe uncontrolled asthma patients accounting for 50% of asthma-related costs. ²⁸

Multiple inflammatory pathways are involved in the pathogenesis of asthma. ^27-29 Eosinophilic asthma, and more broadly, T2 inflammation-driven asthma, accounts for about two-thirds of patients with severe asthma. ²⁹ These patients are typically characterized as having elevated levels of inflammatory biomarkers, including blood eosinophils, serum IgE and FeNO. ^30,31 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. ³¹

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 AZ recording its share of US profits as Collaboration Revenue. Outside of the U.S., AstraZeneca will record product sales, with Amgen recording profit share as Other/Collaboration revenue.

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.

Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average and is also part of the Nasdaq-100 index. In 2021, Amgen was named one of the 25 World's Best Workplaces™ by Fortune and Great Place to Work™ and one of the 100 most sustainable companies in the world by Barron's.

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

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SOURCE Amgen