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

Rhea-AI Summary

AstraZeneca and Amgen announced positive results from the NAVIGATOR Phase III trial of tezepelumab for severe, uncontrolled asthma. The trial met its primary endpoint with a significant reduction in the annualized asthma exacerbation rate (AAER) over 52 weeks compared to placebo. Tezepelumab was well tolerated and showed efficacy in patients with low eosinophil counts. This promising data supports the FDA's Breakthrough Therapy Designation for patients without an eosinophilic phenotype. Severe asthma affects approximately 34 million people globally.

Positive

• Tezepelumab significantly reduced the annualized asthma exacerbation rate (AAER) compared to placebo, demonstrating strong efficacy.
• Well-tolerated safety profile with no significant differences noted between tezepelumab and placebo groups.
• Supports the FDA's Breakthrough Therapy Designation for tezepelumab in severe asthma without eosinophilic phenotype.

Negative

• None.

WILMINGTON, Del.--(BUSINESS WIRE)--AstraZeneca and Amgen today announced positive results from the NAVIGATOR Phase III trial for the potential new medicine tezepelumab in patients with severe, uncontrolled asthma.

NAVIGATOR met the primary endpoint with tezepelumab added to standard of care (SoC) demonstrating a statistically significant and clinically meaningful¹ reduction in the annualized asthma exacerbation rate (AAER) over 52 weeks in the overall patient population, compared to placebo when added to SoC. SoC was medium- or high-dose inhaled corticosteroids (ICS) plus at least one additional controller medication with or without oral corticosteroids (OCS).

In the subgroup of patients with baseline eosinophil counts less than 300 cells per microliter the trial also met the primary endpoint, with tezepelumab demonstrating a statistically significant and clinically meaningful reduction in AAER. Similar reductions in AAER were observed in the subgroup of patients with baseline eosinophil counts less than 150 cells per microliter.

Tezepelumab was very well tolerated in patients with severe asthma. Preliminary analyses show no clinically meaningful differences in safety results between the tezepelumab and placebo groups. Results from the NAVIGATOR trial will be presented at a forthcoming medical meeting.

Severe asthma is a debilitating condition affecting approximately 34 million people worldwide.^2.3 Many severe asthma patients continue to experience symptoms and frequent exacerbations despite the use of high-dose asthma controller medicines, currently available biologic therapies and OCS.^3-5

Professor Andrew Menzies-Gow, Director of the Lung Division, Royal Brompton Hospital, London, UK, and principal investigator of the NAVIGATOR Phase III trial, said: “Due to the complex nature of severe asthma, many patients continue to face debilitating symptoms despite receiving standard of care inhaled medicines and currently approved biologics. Today’s ground-breaking results show that tezepelumab has the potential to transform care for a broad population of severe asthma patients who are underserved today, including those without an eosinophilic phenotype.”

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “Tezepelumab works differently from any other asthma biologic medicine and targets multiple inflammatory pathways that contribute to asthma symptoms and exacerbations. Building on the broad efficacy previously seen with tezepelumab, these are exciting data that bring us one step closer to delivering a medicine to severe asthma patients, including those with low eosinophil counts.”

Tezepelumab is a potential first-in-class medicine that blocks the action of thymic stromal lymphopoietin (TSLP), an epithelial cytokine that plays a key role across the spectrum of asthma inflammation.^6,7 NAVIGATOR is the first Phase III trial to show benefit in severe asthma by targeting TSLP.

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 US Food and Drug Administration Breakthrough Therapy Designation granted to tezepelumab in September 2018 for patients with severe asthma, without an eosinophilic phenotype. Tezepelumab is being developed by AstraZeneca in collaboration with Amgen (see AstraZeneca and Amgen collaboration below).

Severe asthma
Asthma is a heterogeneous disease affecting an estimated 339 million people worldwide.^2,3 Approximately 10% of asthma patients have severe asthma.^3,4 Despite the use of inhaled asthma controller medicine, currently available biologic therapies and OCS, many severe asthma patients remain uncontrolled.^3-5 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.^4,8,9

Severe, uncontrolled asthma is debilitating with patients experiencing frequent exacerbations, significant limitations on lung function and a reduced quality of life.^3,5,10 Patients with severe asthma are at an increased risk of mortality and account for twice as many asthma-related hospitalizations.^11-13 There is also a significant socio-economic burden, with these patients accounting for 50% of asthma-related costs.¹⁴

NAVIGATOR and the PATHFINDER clinical trial program
Building on the Phase IIb PATHWAY trial, the Phase III PATHFINDER program included two trials, NAVIGATOR and SOURCE.^15,16 The program includes additional planned mechanistic and long-term safety trials.

NAVIGATOR is a Phase III, 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 treatment with medium- or high-dose ICS plus at least one additional controller medication with or without OCS. The trial population included approximately equal proportions of patients with high (≥ 300 cells/µL) and low (< 300 cells/µL) 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.^15,17

The primary efficacy endpoint was the annualized asthma exacerbation rate during the 52-week treatment period. Key secondary endpoints included the effect of tezepelumab on lung function, asthma control and health-related quality of life.^15,17

SOURCE is a Phase III 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. The primary endpoint is the categorized percentage reduction from baseline in the daily OCS dose, while not losing asthma control.^16,18

Patients who participated in the NAVIGATOR and SOURCE trials were eligible to continue in DESTINATION, a Phase III extension trial assessing long term safety and efficacy.¹⁹

Tezepelumab
Tezepelumab is a potential 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.^6,7 TSLP is released in response to multiple triggers associated with asthma exacerbations, including allergens, viruses and other airborne particles.^6,7 Expression of TSLP is increased in the airways of patients with asthma and has been correlated with disease severity.^7,20 Blocking TSLP may prevent the release of pro-inflammatory cytokines by immune cells, resulting in the prevention of asthma exacerbations and improved asthma control.^7,20Tezepelumab acts at the top of the inflammation cascade and has the potential to treat a broad population of severe asthma patients regardless of their type of inflammation.^7,20

AstraZeneca and Amgen collaboration
Earlier 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 US and AstraZeneca will record sales in Canada. AstraZeneca’s share of gross profits from tezepelumab in the US will be recognized as collaboration revenue. In all countries outside the US and Canada, AstraZeneca will solely commercialize tezepelumab. AstraZeneca will record all sales outside of the US as product sales and recognize Amgen’s share of gross profit as cost of sales.

AstraZeneca in Respiratory & Immunology
Respiratory & Immunology is one of AstraZeneca’s three therapy areas and is a key growth driver for the Company.

AstraZeneca is an established leader in respiratory care, and its inhaled and biologic medicines reached more than 53 million patients in 2019. Building on a 50-year heritage, the Company aims to transform the treatment of asthma and 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.

About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.

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 US-47026 Last Updated 11/20