FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
Report
of Foreign Issuer
Pursuant
to Rule 13a-16 or 15d-16 of
the
Securities Exchange Act of 1934
For the
month of November 2020
Commission
File Number: 001-11960
AstraZeneca PLC
1
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United
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Tezepelumab
Phase III trial met primary endpoint
This announcement contains inside information
10 November 2020 07:00 GMT
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
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 annualised 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 microlitre 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
microlitre.
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
microlitre 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
hospitalisations.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 programme
Building on the Phase IIb PATHWAY trial, the Phase III PATHFINDER
programme included two trials, NAVIGATOR and
SOURCE.15,16 The
programme includes additional planned mechanistic and long-term
safety trials.
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 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 annualised 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 multicentre, randomised, 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
categorised 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.7,20 Tezepelumab
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 commercialise 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 recognised as
collaboration revenue. In all countries outside the US and Canada,
AstraZeneca will solely commercialise tezepelumab. AstraZeneca will
record all sales outside of the US as product sales and recognise
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.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global,
science-led biopharmaceutical company that focuses on the
discovery, development and commercialisation of prescription
medicines, primarily for the treatment of diseases in three therapy
areas - Oncology, 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 astrazeneca.com and
follow the Company on Twitter @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1. 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.
2. The Global
Asthma Network. The Global Asthma Report 2018. [Online]. Available
at: http://www.globalasthmareport.org/Global%20Asthma%20Report%202018.pdf.
[Last accessed: November 2020].
3. Chung KF, Wenzel SE, Brozek
JL, et
al. International ERS/ATS
guidelines on definition, evaluation and treatment of severe
asthma. Eur Respir
J. 2014; 43:
343-73.
4. Wenzel S. Severe Asthma in
Adults. Am J Respir Crit Care
Med. 2005; 172;
149-60.
5. Peters SP, Ferguson G, Deniz
Y, et
al. Uncontrolled asthma: a
review of the prevalence, disease burden and options for
treatment. Respir Med. 2006; 100 (7): 1139-51.
6. Varricchi G, Pecoraro A,
Marone G, et al. Thymic Stromal Lymphopoietin Isoforms,
Inflammatory Disorders, and Cancer. Front
Immunol. 2018; 9:
1595.
7. Corren J, Parnes JR, Wang
L, et
al. Tezepelumab in Adults
with Uncontrolled Asthma [published correction appears
in N
Engl J Med. 2019 May
23;380(21):2082]. N Engl J
Med. 2017; 377 (10):
936-946.
8. Hyland ME, Masoli M, Lanario
JW, et al. A Possible Explanation for Non-responders,
Responders and Super-responders to Biologics in Severe
Asthma. Explor Res Hypothesis
Med. 2019;
4:35-38.
9. Tran TN, Zeiger RS, Peters SP,
et al. Overlap of atopic, eosinophilic, and TH2-high asthma
phenotypes in a general population with current
asthma. Ann Allergy Asthma
Immunol. 2016;
116:37-42.
10. Fernandes AG, Souza-Machado C, Coelho
RC, et
al. Risk factors for death in
patients with severe asthma. J Bras
Pneumol. 2014; 40 (4):
364-372.
11. 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.
12. Hartert TV, Speroff T, Togias
A, et
al. Risk factors for
recurrent asthma hospital visits and death among a population of
indigent older adults with asthma. Ann Allergy Asthma
Immunol. 2002; 89:
467-73.
13. 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.
14. World Allergy
Organization (WAO). The management of severe asthma: economic
analysis of the cost of treatments for severe asthma. Available
from: https://www.worldallergy.org/educational_programs/world_allergy_forum/anaheim2005/blaiss.php [Last
accessed: November 2020].
15. Clinicaltrials.gov.
Study to Evaluate Tezepelumab in Adults & Adolescents With
Severe Uncontrolled Asthma (NAVIGATOR) [Online]. Available
at: https://clinicaltrials.gov/ct2/show/NCT03347279.
[Last accessed: November 2020].
16. 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].
17. 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.
18. 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.
19. Clinicaltrials.gov.
Extension Study to Evaluate the Safety and Tolerability of
Tezepelumab in Adults and Adolescents With Severe,
Uncontrolled Asthma (DESTINATION) [Online]. Available
at: https://clinicaltrials.gov/ct2/show/NCT03706079.
[Last accessed: November 2020].
20. Li Y, Wang W, LV Z et
al. Elevated Expression of IL-33 and TSLP in the Airways of
Human Asthmatics In Vivo: A Potential Biomarker of Severe
Refractory Disease. The Journal of
Immunology. 2018; 200:
2253-2262.
Adrian Kemp
Company Secretary
AstraZeneca PLC
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.
Date:
10 November 2020
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|