In the pooled analysis, TEZSPIRE, when added to standard of care (SoC), reduced asthma exacerbations in patients, irrespective of baseline blood eosinophil counts, demonstrating consistent efficacy with a 71% (≥300 cells per microliter), 48% (<300 cells per microliter) and 48% (<150 cells per microliter) reduction in the AAER over 52 weeks, compared to placebo added to SoC.1 In the same analysis, TEZSPIRE also demonstrated improvements in AAER in patients regardless of fractional exhaled nitric oxide (FeNO) level and allergy status over 52 weeks, compared to placebo.1
Additionally, in a pre-specified exploratory analysis from NAVIGATOR, TEZSPIRE demonstrated consistent efficacy throughout the year regardless of season.2 Data show that TEZSPIRE reduced the AAER by 63% (winter), 46% (spring), 62% (summer) and 54% (autumn) compared to placebo.2 The proportion of patients with an exacerbation was lower in the TEZSPIRE group than in the placebo group across all seasons.2
"The majority of severe asthma patients have multiple drivers of inflammation, triggered by allergens, viral and bacterial infections, and air pollution, all of which can contribute to ongoing exacerbations. These new results highlight TEZSPIRE's potential to reduce severe asthma exacerbations in patients irrespective of biomarker levels and seasonal triggers," said Dr.
"We're thrilled to continue seeing patients experience fewer asthma attacks following treatment with TEZSPIRE based on results from the latest analyses in the NAVIGATOR and PATHWAY trials," said
These results are being presented at the 2022
TEZSPIRE is approved in
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
Known hypersensitivity to tezepelumab-ekko or excipients.
WARNINGS AND PRECAUTIONS
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.
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
The PATHFINDER clinical trial program for TEZSPIRE included the Phase 2b PATHWAY and Phase 3 NAVIGATOR trials.3-5 The program also includes an oral corticosteroid sparing trial, a mechanistic trial and a long-term safety trial. 6-9
PATHWAY is a Phase 2b, randomized, double-blind, parallel group, placebo-controlled, 52-week trial designed to evaluate the efficacy and safety of three dose regimens of TEZSPIRE, 70mg and 210mg every four weeks and 280mg 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-agonist with or without oral corticosteroids and additional asthma controllers.3
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 plus at least one additional controller medication with or without daily OCS treatment. The trial population included approximately equal proportions of patients with high (≥300 cells per microliter) and low (<300 cells per microliter) blood eosinophil counts. The trial comprised a five-to-six-week screening period, a 52-week treatment period and a 12-week post-treatment follow-up period. All patients received their prescribed controller medications without change throughout the trial.4
The primary efficacy endpoint was the annualized asthma exacerbation rate (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.4
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).4 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 NAVIGATOR results showed a statistically significant and clinically meaningful reduction in the primary endpoint of AAER over 52 weeks in the overall patient population.4 Clinically meaningful reductions in AAER compared to placebo were observed in the TEZSPIRE-treated patients irrespective of blood eosinophil counts, FeNO level and allergy status.4 There were no clinically meaningful differences in safety results between the TEZSPIRE and placebo groups in the NAVIGATOR trial.4 The most frequently reported adverse events for TEZSPIRE were nasopharyngitis, upper respiratory tract infection and headache.4
NAVIGATOR and PATHWAY pooled post-hoc analysis:
AAER results over 52 weeks
TEZSPIRE added to SoC versus placebo added to SoC
Baseline blood eosinophil counts (≥300 cells per microliter)
71% reduction (95% CI: 62, 78)
Baseline blood eosinophil counts (≥150 to <300 cells per microliter)
48% reduction (95% CI: 28, 62)
Baseline blood eosinophil counts (<150 cells per microliter)
48% reduction (95% CI: 26, 64)
FeNO levels (<25 parts per billion)
40% reduction (95% CI: 21, 54)
FeNO levels (≥25 parts per billion)
70% reduction (95% CI: 62, 76)
Positive allergy to perennial aeroallergens
62% reduction (95% CI: 53, 70)
Negative allergy to perennial aeroallergens
54% reduction (95% CI: 38, 66)
CI: Confidence interval
NAVIGATOR pre-specified seasonality analysis:
AAER results over 52 weeks
63% reduction (95% CI: 52, 72)
46% reduction (95% CI: 26, 61)
62% reduction (95% CI: 48, 73)
54% reduction (95% CI: 41, 64)
CI: Confidence interval
NAVIGATOR is the first Phase 3 trial to show benefit in severe asthma irrespective of eosinophils by targeting the cytokine thymic stromal lymphopoietin (TSLP).4 These results support the FDA Breakthrough Therapy Designation granted to TEZSPIRE in
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.10,11 TSLP is released in response to multiple triggers associated with asthma exacerbations, including allergens, viruses and other airborne particles.10,11
Expression of TSLP is increased in the airways of patients with asthma and has been correlated with disease severity.10,12 Blocking TSLP may prevent the release of pro-inflammatory cytokines by immune cells, resulting in the prevention of asthma exacerbations and improved asthma control.10,12 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.10,12
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
About Severe Asthma
Globally, there are approximately 2.5 million patients with severe asthma who are uncontrolled or biologic eligible, with approximately 1.3 million in the
Multiple inflammatory pathways are involved in the pathogenesis of asthma.21-23 Eosinophilic asthma, and more broadly, T2 inflammation-driven asthma, accounts for about two-thirds of patients with severe asthma.23 These patients are typically characterized as having elevated levels of inflammatory biomarkers, including blood eosinophils, serum IgE and FeNO.24,25 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.25
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.
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.
Amgen Forward-Looking Statements
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