Trial also met the primary endpoint in
patients with low levels of eosinophils
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
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
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
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
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
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
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
- Bonini M, Di Paolo M, Bagnasco D, et al. Minimal clinically
important difference for asthma endpoints: an expert consensus
report. Eur Respir Rev. 2020; 29: 190137.
- The Global Asthma Network. The Global Asthma Report 2018.
[Online]. Available at:
[Last accessed: November 2020].
- Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS
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Severe Asthma. Explor Res Hypothesis Med. 2019; 4:35–38.
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eosinophilic, and TH2-high asthma phenotypes in a general
population with current asthma. Ann Allergy Asthma Immunol. 2016;
- Fernandes AG, Souza-Machado C, Coelho RC, et al. Risk factors
for death in patients with severe asthma. J Bras Pneumol. 2014; 40
- Chastek B, et al.Economic Burden of Illness Among Patients with
Severe Asthma in a Managed Care Setting. J Manag Care Spec Pharm.
2016; 22: 848–861.
- Hartert TV, Speroff T, Togias A, et al. Risk factors for
recurrent asthma hospital visits and death among a population of
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- Price D, Fletcher M, van der Molen T. Asthma control and
management in 8,000 European patients: the REcognise Asthma and
LInk to Symptoms and Experience (REALISE) survey. NPJ Prim Care
Respir Med. 2014; 12; 24: 14009.
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asthma: economic analysis of the cost of treatments for severe
asthma. Available from:
[Last accessed: November 2020].
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& Adolescents With Severe Uncontrolled Asthma (NAVIGATOR)
[Online]. Available at:
https://clinicaltrials.gov/ct2/show/NCT03347279. [Last accessed:
- Clinicaltrials.gov. Study to Evaluate the Efficacy and Safety
of Tezepelumab in Reducing Oral Corticosteroid Use in Adults With
Oral Corticosteroid Dependent Asthma (SOURCE) [Online]. Available
at: https://clinicaltrials.gov/ct2/show/NCT03406078. [Last
accessed: November 2020].
- Menzies-Gow A, Colice G, Griffiths JM et al. NAVIGATOR: a phase
3 multicentre, randomized, double-blind, placebo-controlled,
parallel-group trial to evaluate the efficacy and safety of
tezepelumab in adults and adolescents with severe, uncontrolled
asthma. Respir Res. 2020; 21(1): 266.
- Weschler ME, Colice G, Griffiths JM et al. SOURCE: A Phase 3,
multicentre, randomized, double-blind, placebo-controlled, parallel
group trial to evaluate the efficacy and safety of Tezepelumab in
reducing oral corticosteroid use in adults with oral corticosteroid
dependent asthma. Respir Res. 2020; 21(1), 264.
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Tolerability of Tezepelumab in Adults and Adolescents With Severe,
Uncontrolled Asthma (DESTINATION) [Online]. Available at:
https://clinicaltrials.gov/ct2/show/NCT03706079. [Last accessed:
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US-47026 Last Updated 11/20
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