New data further reinforce efficacy of Tezspire in a broad population of severe asthma patients

Analyses from NAVIGATOR and PATHWAY trials presented at the 2022 AAAAI Annual Meeting

Results from a pooled post-hoc analysis of the pivotal NAVIGATOR Phase III and PATHWAY Phase IIb trials showed AstraZeneca and Amgen’s Tezspire (tezepelumab) demonstrated reductions in the annualised asthma exacerbation rate (AAER) across biomarker subgroups of patients with severe asthma.1 These findings support the role of Tezspire as a first-in-class treatment for a broad population of patients with severe asthma, irrespective of biomarker levels.1

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 microlitre), 48% (<300 cells per microlitre) and 48% (<150 cells per microlitre) 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

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

Dr. Jonathan Corren, clinical faculty member at the David Geffen School of Medicine, UCLA, and principal investigator of the PATHWAY trial, said: “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.” 

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: "The reductions in exacerbations seen across these patient subgroups add to the body of evidence supporting Tezspire’s approval as the first and only biologic without phenotypic or biomarker limitation. Taken together with the positive efficacy results seen regardless of season, these results further reinforce our belief that Tezspire has the potential to transform care for a broad population of severe asthma patients.”

These results are being presented at the 2022 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.1,2

Tezspire is approved in the US for the treatment of severe asthma and is under regulatory review in the EU, Japan and several other countries around the world.3


Severe asthma
Asthma is a heterogeneous disease affecting an estimated 339 million people worldwide.4,5 Up to 10% of asthma patients have severe asthma.5,6 Despite the use of inhaled asthma controller medicine, currently available biologic therapies and oral corticosteroids (OCS), many severe asthma patients remain uncontrolled.5-7 Due to the complexity of severe asthma, many patients have unclear or multiple drivers of inflammation and may not qualify for or respond well to a current biologic medicine.6-9

Severe, uncontrolled asthma is debilitating with patients experiencing frequent exacerbations, significant limitations on lung function and a reduced quality of life.5,6,10 Patients with severe asthma are at an increased risk of mortality and compared to patients with persistent asthma have twice the risk of asthma-related hospitalisations.10-13 There is also a significant socio-economic burden, with these patients accounting for approximately 50% of asthma-related costs.14

Clinical trials
The PATHFINDER clinical trial programme for Tezspire included the Phase IIb PATHWAY and Phase III NAVIGATOR trials.15-17 The programme also includes an oral corticosteroid sparing trial, a mechanistic trial and a long-term safety trial.18-21

PATHWAY is a Phase IIb, randomised, 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.15

NAVIGATOR is a Phase III, randomised, 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 microlitre) and low (<300 cells per microlitre) 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.16

The primary efficacy endpoint was the annualised 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.16

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).16 These are inflammatory biomarkers used by clinicians to inform treatment options and involve tests analysing 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.16 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.16 There were no clinically meaningful differences in safety results between the Tezspire and placebo groups in the NAVIGATOR trial.16 The most frequently reported adverse events for Tezspire were nasopharyngitis, upper respiratory tract infection and headache.16

The findings from the pooled analysis build on the PATHWAY and NAVIGATOR results previously published in The New England Journal of Medicine.15,16

NAVIGATOR and PATHWAY pooled post-hoc analysis:
AAER in severe, uncontrolled asthma patients1


AAER results over 52 weeks

Tezspire added to SoC versus placebo added to SoC (relative risk reduction and annualised exacerbation rates)

Baseline blood eosinophil counts (≥300 cells per microlitre)

71% reduction (95% CI: 62, 78)

·     Tezspire: 0.68

·     Placebo: 2.35

Baseline blood eosinophil counts (≥150 to <300 cells per microlitre)

48% reduction (95% CI: 28, 62)

·     Tezspire: 0.81

·     Placebo: 1.56

Baseline blood eosinophil counts (<150 cells per microlitre)

48% reduction (95% CI: 26, 64)

·     Tezspire: 0.88

·     Placebo: 1.70

FeNO levels (<25 parts per billion)

40% reduction (95% CI: 21, 54)

·     Tezspire: 0.84

·     Placebo: 1.40

FeNO levels (≥25 parts per billion)

70% reduction (95% CI: 62, 76)

·     Tezspire: 0.72

·     Placebo: 2.39

Positive allergy to perennial aeroallergens

62% reduction (95% CI: 53, 70)

·     Tezspire: 0.72

·     Placebo: 1.92

Negative allergy to perennial aeroallergens

54% reduction (95% CI: 38, 66)

·     Tezspire: 0.89

·     Placebo: 1.95

CI: Confidence interval

NAVIGATOR pre-specified seasonality analysis:
AAER in severe, uncontrolled asthma patients2


AAER results over 52 weeks

Tezspire added to SoC versus placebo added to SoC


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 III trial to show benefit in severe asthma irrespective of eosinophils by targeting TSLP.16 These results support the FDA 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 US for the treatment of asthma by the FDA.

Patients who participated in our Phase III trials were eligible to continue in DESTINATION, a Phase III extension trial assessing long-term safety and efficacy.20

Tezspire (tezepelumab) is being developed by AstraZeneca in collaboration with Amgen as a first-in-class human monoclonal antibody that inhibits the action of TSLP, a key epithelial cytokine that sits at the top of multiple inflammatory cascades and is critical in the initiation and persistence of allergic, eosinophilic and other types of airway inflammation associated with severe asthma, including airway hyperresponsiveness.15,22 TSLP is released in response to multiple triggers associated with asthma exacerbations, including allergens, viruses and other airborne particles.15,22 Expression of TSLP is increased in the airways of patients with asthma and has been correlated with disease severity.15,23 Blocking TSLP may prevent the release of pro-inflammatory cytokines by immune cells, resulting in the prevention of asthma exacerbations and improved asthma control. 15,16,23 Tezspire acts at the top of the inflammation cascade and has the potential to help address a broad population of severe asthma patients irrespective of biomarker levels.15,16

Tezspire is approved in the US for the add-on maintenance treatment of adult and paediatric patients aged 12 years and older with severe asthma.3 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).24-26 In October 2021, tezepelumab was granted Orphan Drug Designation by the FDA for the treatment of EoE.

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

AstraZeneca in Respiratory & Immunology
Respiratory & Immunology, part of BioPharmaceuticals, is one of AstraZeneca’s main disease areas and is a key growth driver for the Company.

AstraZeneca is an established leader in respiratory care with a 50-year heritage. The Company aims to transform the treatment of asthma and chronic obstructive pulmonary disease (COPD) by focusing on earlier biology-led treatment, eliminating preventable asthma attacks, and removing COPD as a top-three leading cause of death. The Company’s early respiratory research is focused on emerging science involving immune mechanisms, lung damage and abnormal cell-repair processes in disease and neuronal dysfunction.

With common pathways and underlying disease drivers across respiratory and immunology, AstraZeneca is following the science from chronic lung diseases to immunology-driven disease areas. The Company’s growing presence in immunology is focused on five mid- to late-stage franchises with multi-disease potential, in areas including rheumatology (including systemic lupus erythematosus), dermatology, gastroenterology, and systemic eosinophilic-driven diseases. AstraZeneca’s ambition in Respiratory & Immunology is to achieve disease modification and durable remission for millions of patients worldwide.

AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit and follow the Company on Twitter @AstraZeneca.

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Veeva ID: Z4-41261
Date of Preparation: February 2022