a1228w
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 December 2021
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Tezspire
approved in the US for severe asthma
20 December 2021 07:05 GMT
Tezspire (tezepelumab) approved
in the US for severe asthma
First and only biologic to consistently and significantly reduce
exacerbations in a broad population of severe asthma
patients
Only biologic for severe asthma approved with no phenotype or
biomarker limitations
AstraZeneca and Amgen's Tezspire (tezepelumab-ekko) has been approved in the
US for the add-on maintenance treatment of adult and paediatric
patients aged 12 years and older with severe
asthma.1
Tezspire was approved
following a Priority
Review by the US Food and
Drug Administration (FDA) and based on results from the
PATHFINDER clinical trial programme. The application included
results from the pivotal NAVIGATOR Phase III trial in
which Tezspire demonstrated superiority across every
primary and key secondary endpoint in patients with severe asthma,
compared to placebo, when added to standard
therapy.2
Tezspire is a
first-in-class biologic for severe asthma that acts at the top of
the inflammatory cascade by targeting thymic stromal lymphopoietin
(TSLP), an epithelial cytokine.2-5 It
is the first and only biologic to consistently and significantly
reduce asthma exacerbations across Phase II and III clinical trials
which included a broad population of severe asthma patients
irrespective of key biomarkers, including blood eosinophil counts,
allergic status and fractional exhaled nitric oxide
(FeNO).2,3,6-13 Tezspire is
the only biologic approved for severe asthma with no phenotype
(e.g. eosinophilic or allergic) or biomarker limitation within its
approved label.1
Professor Andrew Menzies-Gow, Director of the Lung Division, Royal
Brompton Hospital, London, UK, and principal investigator of the
NAVIGATOR trial, said: "Due to the complex
and heterogeneous nature of severe asthma and despite
recent advances, many patients continue to experience frequent
exacerbations, an increased risk of hospitalisation and a
significantly reduced quality of
life. Tezspire represents
a much-needed new treatment for the many patients who remain
underserved and continue to struggle with severe, uncontrolled
asthma."
Tonya Winders, President and CEO of Allergy & Asthma
Network, and President of the Global Allergy and Airways Patient
Platform, said: "Severe asthma continues to have a debilitating
impact on many of the 34 million people living with the disease
worldwide, affecting their breathing and limiting aspects of
day-to-day life. The approval of Tezspire is long-awaited positive news for the asthma
community. For the first time, many people living with severe
asthma have the opportunity to receive treatment regardless of the
cause of their inflammation."
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, AstraZeneca, said: "Today's positive decision marks
the first time the FDA has approved a biologic for asthma without
phenotypic limitation and irrespective of biomarker levels. With
the approval of Tezspire, physicians will now be able to offer an
important new treatment that has the potential to transform care
for a broad population of severe asthma
patients."
In clinical studies, the most common adverse reactions in patients
who received Tezspire were pharyngitis, arthralgia and back
pain.1
Results from the NAVIGATOR Phase III trial were published
in The
New England Journal of Medicine in May 2021. There were no clinically
meaningful differences in safety results between
the Tezspire and placebo groups in the NAVIGATOR
trial.2
The application for Tezspire was granted Priority Review, a
designation given to applications for medicines that offer
significant advantages over available options by demonstrating
safety or efficacy improvements, preventing serious conditions, or
enhancing patient compliance.14
Tezspire is under
regulatory review in the EU, Japan and several other countries
around the world.
Notes
Severe asthma
Asthma is a heterogeneous disease affecting an estimated 339
million people worldwide.15,16 Approximately
10% of asthma patients have severe asthma.16,17 Despite
the use of inhaled asthma controller medicine, currently available
biologic therapies and oral corticosteroids (OCS), many severe
asthma patients remain uncontrolled.16-18 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.17-20
Severe, uncontrolled asthma is debilitating with patients
experiencing frequent exacerbations, significant limitations on
lung function and a reduced quality of life.16,17,21 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.22-24 There
is also a significant socio-economic burden, with these patients
accounting for approximately 50% of asthma-related
costs.25
Clinical trials
In addition to the Phase IIb PATHWAY trial, the PATHFINDER
programme included two Phase III trials,
NAVIGATOR2,26 and
SOURCE.27,28 The
programme also includes additional mechanistic and long-term safety
trials.29,30
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.2
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.2
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).2 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).
There were no clinically meaningful differences in safety results
between the Tezspire and placebo groups in the NAVIGATOR
trial.2 The
most frequently reported adverse events
for Tezspire were
nasopharyngitis, upper respiratory tract infection and
headache.2
NAVIGATOR is the first Phase III trial to show benefit in severe
asthma irrespective of eosinophils by targeting
TSLP.2 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.29
Tezspire
Tezspire (tezepelumab) is
being developed by AstraZeneca in collaboration with Amgen as 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, including airway
hyperresponsiveness.3,4 TSLP
is released in response to multiple triggers associated with asthma
exacerbations, including allergens, viruses and other airborne
particles.3,4 Expression
of TSLP is increased in the airways of patients with asthma and has
been correlated with disease severity.3,5 Blocking
TSLP may prevent the release of pro-inflammatory cytokines by
immune cells, resulting in the prevention of asthma exacerbations
and improved asthma control.2,3,5 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.2,3
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). 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 commercialize 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
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 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. Tezspire (tezepelumab) US prescribing information;
2021.
2. Menzies-Gow
A, et
al. Tezepelumab in Adults
and Adolescents with Severe, Uncontrolled
Asthma. N Engl J
Med. 2021;384: 1800-1809.
DOI: 10.1056/NEJMoa2034975.
3. Corren J, et al. Tezepelumab in adults with uncontrolled asthma
[supplementary appendix; updated April 18,
2019]. N Engl J
Med. 2017;377:
936-946.
4. Varricchi
G, et
al. Thymic Stromal
Lymphopoietin Isoforms, Inflammatory Disorders, and
Cancer. Front
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5. Li Y, et al. Elevated Expression of IL-33 and TSLP in the
Airways of Human Asthmatics In Vivo: A Potential Biomarker of
Severe Refractory Disease. J Immunol. 2018;200: 2253-2262.
6. Hanania
NA, et
al. Omalizumab in severe
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7. Yancey SW, et al. Disease burden and efficacy of mepolizumab in
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≥150-300 cells/lL. Respir Med. 2019; 151: 139-141.
8. FitzGerald
JM, et
al. Predictors of enhanced
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Moderate-to-Severe Uncontrolled Asthma. N Engl J
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10. Ortega HG, et al; on behalf of the MENSA Investigators.
Mepolizumab treatment in patients with severe eosinophilic
asthma. N Engl J
Med.
2014;371(13):1198-207.
11. Bleecker ER, et al, on behalf of the SIROCCO study investigators.
Efficacy and safety of benralizumab for patients with severe asthma
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long-acting beta2-agonists (SIROCCO): a randomised, multicentre,
placebo-controlled phase 3 trial. Lancet 2016: 388 (10056):
2115-2127.
12. FitzGerald JM, et al, on behalf of the CALIMA study investigators.
Benralizumab, an anti-interleukin-5 receptor alpha monoclonal
antibody, as add-on treatment for patients with severe,
uncontrolled, eosinophilic asthma (CALIMA): a randomised,
double-blind, placebo-controlled phase 3
trial. Lancet. 2016: 388(10056):
2128-2141.
13. Wenzel S, et al. Dupilumab efficacy and safety in adults with
uncontrolled persistent asthma despite use of medium-to-high-dose
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trial. Lancet. 2016 Jul
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14. US
Food and Drug Administration. Priority Review. Available
at: https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review.
[Last accessed: December 2021].
15. The Global Asthma
Network. The Global Asthma Report 2018. [Online]. Available
at: http://globalasthmareport.org/resources/Global_Asthma_Report_2018.pdf.
[Last accessed: December 2021].
16. Chung KF, et al. International ERS/ATS guidelines on definition,
evaluation and treatment of severe asthma. Eur Respir
J. 2014; 43 (2):
343-373.
17. Wenzel S. Severe asthma in
adults. Am J Respir Crit Care
Med. 2005; 172:
149-160.
18. Peters SP, et al. Uncontrolled asthma: a review of the prevalence,
disease burden and options for treatment. Respir Med
2006: 100 (7):
1139-51.
19. Hyland ME, 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.
20. Tran TN, et al. Overlap of atopic, eosinophilic, and
TH2-high asthma phenotypes in a general population with current
asthma. Ann Allergy Asthma
Immunol. 2016; 116:
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21. Fernandes AG, et al. Risk factors for death in patients with severe
asthma. J Bras
Pneumol. 2014; 40:
364-372.
22. 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:
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23. Hartert TV, et al. Risk factors for recurrent asthma hospital
visits and death among a population of indigent older adults with
asthma. Ann Allergy Asthma
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24. Price D, et al. Asthma control and management in 8,000
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25.
World Allergy Organization (WAO). The management of severe asthma:
economic analysis of the cost of treatments for severe asthma.
Available at:
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[Last accessed: December 2021].
26. Menzies-Gow A, 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: 266.
27. Wechsler ME, et al. Oral corticosteroid-sparing effect of
tezepelumab in adults with severe asthma. Am J Respir Crit Care
Med. 2021;203:
A1197.
28. Weschler ME, et al. SOURCE: A Phase 3, multicentre, randomized,
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29.
Clinicaltrials.gov. Extension Study to Evaluate the Safety and
Tolerability of Tezepelumab in Adults and Adolescents With Severe,
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December 2021].
30.
Diver S et al. Effect of tezepelumab on airway inflammatory cells,
remodelling, and hyperresponsiveness in patients with
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December 2021].
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:
20 December 2021
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|