a5305t
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 July 2022
Commission
File Number: 001-11960
AstraZeneca PLC
Enhertu
granted Priority Review for HER2-low mBC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
Indicate
by check mark whether the registrant files or will file annual
reports under cover of Form 20-F or Form 40-F.
Form
20-F X Form 40-F __
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(1):
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(7): ______
Indicate
by check mark whether the registrant by furnishing the information
contained in this Form is also thereby furnishing the information
to the Commission pursuant to Rule 12g3-2(b) under the Securities
Exchange Act of 1934.
Yes __
No X
If
“Yes” is marked, indicate below the file number
assigned to the Registrant in connection with Rule 12g3-2(b):
82-_____________
AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Tezspire recommended for EU approval in asthma
25 July 2022 07:10 BST
Tezspire recommended
for approval in the EU by CHMP for the treatment
of severe
asthma
First and only biologic recommended for EU approval in patients
with severe asthma with no phenotype or biomarker
limitations
AstraZeneca's Tezspire (tezepelumab) has been recommended for
marketing authorisation in the European Union (EU) as an add-on
therapy in patients 12 years and older with severe asthma who are
inadequately controlled with high dose inhaled corticosteroids plus
another medicinal product for maintenance
treatment.
The Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency based its positive opinion on results
from the PATHFINDER clinical trial programme. The marketing
authorisation 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.1
Tezspire is the first and
only biologic 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 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).1,2
Dr. Stephanie Korn, Senior Physician in Pneumology and Respiratory
Medicine at IKF Pneumologie Mainz and Thoraxklinik Heidelberg,
Germany, and investigator for the NAVIGATOR trial said: "Due
to the complexity of severe asthma, about 60% of patients have
multiple drivers of inflammation. Tezspire is a first-in-class biologic
acting at the top of the inflammation cascade and a much-needed
potential treatment for patients who continue to struggle with
severe, uncontrolled asthma."
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, AstraZeneca, said: "Despite recent advances in treatment,
many asthma patients continue to experience debilitating symptoms,
an increased risk of hospitalisation, and even death. The only
biologic recommended for EU approval in severe asthma patients with
no phenotype or biomarker limitation, Tezspire has consistently and significantly reduced
exacerbations in clinical trials, and has the potential to
transform care for a broad population of severe asthma
patients."
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.1
In clinical trials, the most common adverse events in patients who
received Tezspire were pharyngitis, rash, arthralgia and
injection site reactions.5
Tezspire was
approved as an add-on maintenance treatment of adult and
paediatric patients aged 12 years and older with severe
asthma in the US in December 2021 and is under
regulatory review in Japan and many other 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.
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.22
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.6 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;18:105-112.
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;43:343-373.
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 2006:100:1139-1151.
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;89:467-473.
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. Evaluation of the
oral corticosteroid-sparing effect of tezepelumab in adults with
oral corticosteroid-dependent asthma (SOURCE): a randomised,
placebo-controlled, phase 3 study. Lancet Respir
Med. 2022;S2213-S2600(21):00537-3.
21. Wechlser 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;9:1299-1312.
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:
25 July 2022
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|