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 September 2022
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 EU for severe asthma
21
September 2022 07:00 BST
Tezspire approved in
the EU for the treatment of severe
asthma
First and only biologic approved in the EU in patients with severe
asthma with no phenotype or biomarker limitations
AstraZeneca's Tezspire (tezepelumab) has been approved in the
European Union (EU) as an add-on maintenance treatment in patients
12 years and older with severe asthma who are inadequately
controlled with high dose inhaled corticosteroids plus another
medicinal product.
The approval by the European Commission was based
on results from the PATHFINDER clinical trial programme, which
included 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.1 The
approval follows the recommendation by
The Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency in July 2022.
Tezspire is the first and only biologic approved in
Europe for severe asthma that acts at the top of the inflammatory
cascade by blocking thymic stromal lymphopoietin (TSLP), an
epithelial cytokine.1-4 Tezspire consistently
and significantly reduced asthma exacerbations across the PATHWAY
Phase II and the NAVIGATOR Phase 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).1,2
Professor Guy Brusselle, Department of Respiratory
Medicine, Ghent University Hospital, Ghent, Belgium, said: "Severe
asthma is a complex disease given approximately 60% of patients
have multiple drivers of inflammation. With the European approval
of Tezspire, a first-in-class biologic acting at the top of
the inflammation cascade, we have an opportunity to treat a broader
population of patients with severe asthma, fulfilling a high unmet
need in this disease."
Mene Pangalos, Executive Vice President,
BioPharmaceuticals R&D, AstraZeneca, said: "Severe asthma
continues to have a debilitating impact for people living with the
disease, with many patients experiencing frequent exacerbations, an
increased risk of hospitalisation and a significantly reduced
quality of life. Tezspire is now the first and only biologic approved
in Europe for patients with severe asthma with no phenotype or
biomarker limitation and we look forward to bringing this important
medicine to patients as quickly as possible."
In clinical trials, the most common adverse events
in patients who received Tezspire were pharyngitis, rash, arthralgia and
injection site reactions.5
Results from the NAVIGATOR Phase III trial were
published in The
New England Journal of Medicine in May 2021.
Tezspire has been approved in
the US and other
countries for the treatment of severe asthma, and regulatory
reviews are ongoing in additional countries around the
world.6
Notes
Severe asthma
Asthma is a heterogeneous disease affecting
approximately 14 million people living with the disease in the
European Union and an estimated 339 million people
worldwide.7,8 Up
to 10% of asthma patients have severe asthma.9,10 Despite
the use of inhaled asthma controller medicine, currently available
biologic therapies and oral corticosteroids (OCS), many severe
asthma patients remain uncontrolled.9-11 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.10-13
Severe, uncontrolled asthma is debilitating with
patients experiencing frequent exacerbations, significant
limitations on lung function and a reduced quality of
life.9,10,14 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.15-17 There
is also a significant socio-economic burden, with these patients
accounting for approximately 50% of asthma-related
costs.18
Clinical trials
In addition to the Phase IIb PATHWAY trial, the
PATHFINDER programme included two Phase III trials,
NAVIGATOR1,19 and
SOURCE.20,21 The
programme also includes additional mechanistic and long-term safety
trials.22,23
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.1
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.1
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).1 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.1 The
most frequently reported adverse events
for Tezspire were
nasopharyngitis, upper respiratory tract infection and
headache.1
NAVIGATOR is the first Phase III trial to show
benefit in severe asthma irrespective of eosinophils by targeting
TSLP.1 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.
Tezspire
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.2,3 TSLP
is released in response to multiple triggers associated with asthma
exacerbations, including allergens, viruses and other airborne
particles.2,3 Expression
of TSLP is increased in the airways of patients with asthma and has
been correlated with disease severity.2,4 Blocking
TSLP may prevent the release of pro-inflammatory cytokines by
immune cells, resulting in the prevention of asthma exacerbations
and improved asthma control.1,2,4 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.1,2
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.5 Tezspire is
also in development for other potential indications including
chronic obstructive pulmonary disease (COPD), 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 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
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. 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.
2. Corren J, et al. Tezepelumab in adults with uncontrolled asthma
[supplementary appendix; updated April 18,
2019]. N Engl J
Med. 2017;377:
936-946.
3. Varricchi
G, et
al. Thymic Stromal
Lymphopoietin Isoforms, Inflammatory Disorders, and
Cancer. Front
Immunol. 2018; 9:
1595.
4. 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.
5. European Medicines
Agency. Tezspire Summary
of Committee for Medicinal Products for Human Use Opinion Available
at: https://www.ema.europa.eu/en/medicines/human/summaries-opinion/tezspire [Last
accessed: July 2022].
6. Tezspire (tezepelumab) US prescribing information;
2021.
7. Demoly
P, et
al.
Prevalence of asthma control among adults in France, Germany,
Italy, Spain and the UK. Eur
Respir Rev. 2009; 18 (112):
105-12.
8. The
Global Asthma Network. The Global Asthma Report 2018. [Online].
Available at: http://globalasthmareport.org/resources/Global_Asthma_Report_2018.pdf.
[Last accessed: July 2022].
9. Chung
KF, et
al.
International ERS/ATS guidelines on definition, evaluation and
treatment of severe asthma. Eur
Respir J.
2014; 43 (2): 343-373.
10. Wenzel S. Severe asthma
in adults. Am
J Respir Crit Care Med. 2005; 172:
149-160.
11. Peters
SP, et
al.
Uncontrolled asthma: a review of the prevalence, disease burden and
options for treatment. Respir
Med 2006: 100
(7): 1139-51.
12. 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.
13. 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:
37-42.
14. Fernandes AG, et al. Risk factors for death in patients with severe
asthma. J Bras
Pneumol. 2014; 40:
364-372.
15. 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.
16. 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
Immunol. 2002;89:
467-73.
17. Price D, et al. 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; 24:
14009.
18. World Allergy
Organization (WAO). The management of severe asthma: economic
analysis of the cost of treatments for severe asthma. Available
at: https://www.worldallergy.org/educational_programs/world_allergy_forum/anaheim2005/blaiss.php.
[Last accessed: July 2022].
19. 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.
20. Wechsler ME, et al. Oral corticosteroid-sparing effect of
tezepelumab in adults with severe asthma. Am J Respir Crit Care
Med. 2021;203:
A1197.
21. Weschler ME, 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: 264.
22. 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: July 2022].
23. Diver S, et al. Effect of tezepelumab on airway inflammatory
cells, remodelling, and hyperresponsiveness in patients with
moderate-to-severe uncontrolled asthma (CASCADE): a double-blind,
randomised, placebo-controlled, phase 2
trial. Lancet Respir
Med. 2021; 9 (11):
1299-1312.
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:
21 September 2022
|
|
By: /s/
Adrian Kemp
|
|
|
Name:
Adrian Kemp
|
|
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Title:
Company Secretary
|
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