a5425e
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 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.
Tezepelumab
granted FDA Priority Review for asthma
8 July 2021 07:00 BST
Tezepelumab regulatory submission accepted and granted FDA Priority
Review in the US for the treatment of patients with
asthma
Tezepelumab is the first and only biologic to consistently and
significantly reduce asthma exacerbations in a broad population
across Phase II and III clinical trials
AstraZeneca's Biologics License Application (BLA) for tezepelumab
has been accepted and granted Priority Review for the treatment of
asthma from the US Food and Drug Administration
(FDA). Tezepelumab is being developed by AstraZeneca in
collaboration with Amgen.
The FDA grants Priority Review to applications for medicines that
offer significant advantages over available options by
demonstrating safety or efficacy improvements, preventing serious
conditions, or enhancing patient compliance.1 The
Prescription Drug User Fee Act date, the FDA action date for their
regulatory decision, is during the first quarter of
2022.
Despite recent advances in severe asthma, many patients may not
qualify for or respond well to current biologic
medicines.2-5 Patients
with severe, uncontrolled asthma experience frequent exacerbations,
significant limitations on lung function and a reduced quality of
life.2,6,7
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, said: "This decision brings us a step closer to delivering
a much-needed, first-in-class medicine for asthma patients, many of
whom remain uncontrolled and at risk of asthma attacks despite the
availability of inhaled and biologic medicines. Tezepelumab has
demonstrated reductions in exacerbations irrespective of blood
eosinophil counts, allergy status and fractional exhaled nitric
oxide, and has the potential to transform treatment for a broad
population of severe asthma patients."
The BLA was based on results from the PATHFINDER clinical
trials programme, including results from the pivotal NAVIGATOR
Phase III trial. In NAVIGATOR, tezepelumab demonstrated superiority
across every primary and key secondary endpoint, compared to
placebo, in a broad population of patients with uncontrolled asthma
while receiving treatment with medium- or high-dose inhaled
corticosteroids (ICS) plus at least one additional controller
medicine with or without oral corticosteroids
(OCS).8
There were no clinically meaningful differences in safety results
between the tezepelumab and placebo groups in the NAVIGATOR
trial.8 The
most frequently reported adverse events with tezepelumab were
nasopharyngitis, upper respiratory tract infection and
headache.8
Results from the NAVIGATOR Phase III trial were published
in The
New England Journal of Medicine in May 2021.
Tezepelumab received Breakthrough Therapy
Designation for patients
with severe asthma, without an eosinophilic phenotype in September
2018.
Severe asthma
Asthma is a heterogeneous disease affecting an estimated 339
million people worldwide.6,9 Approximately
10% of asthma patients have severe asthma.2,6 Despite
the use of inhaled asthma controller medicine, currently available
biologic therapies and oral corticosteroids (OCS), many severe
asthma patients remain uncontrolled.2,3,6 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.2-5
Severe, uncontrolled asthma is debilitating with patients
experiencing frequent exacerbations, significant limitations on
lung function and a reduced quality of life.2,6,7 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.10-12 There
is also a significant socio-economic burden, with these patients
accounting for 50% of asthma-related costs.13
Clinical trials
Building on the Phase IIb PATHWAY trial, the Phase III PATHFINDER
programme included two trials, NAVIGATOR8,14 and
SOURCE.15,16 The
programme includes additional planned mechanistic and long-term
safety trials.17-19
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 ICS plus at least one additional controller
medicine 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 medicines
without change throughout the trial.8
The primary efficacy endpoint was the annualised asthma
exacerbation rate (AAER) 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.8
NAVIGATOR primary endpoints8
|
Endpoint
|
Timepoint
|
Annual exacerbation rate
|
Results
Tezepelumab added to SoC vs placebo added to SoC
|
Tezepelumab
|
Placebo
|
AAER -
Overall patient population
|
Over 52 weeks
|
0.93 (95% CI: 0.80-1.07)
|
2.10 (95% CI: 1.84-2.39)
|
56% reduction (95% CI: 47-63%; p<0.001)
|
AAER - Baseline eosinophil counts <300
cells/µL
|
Over 52 weeks
|
1.02 (95% CI: 0.84-1.23)
|
1.73 (95% CI: 1.46-2.05)
|
41% reduction (95% CI: 25-54%; p<0.001)
|
CI: confidence interval
As part of prespecified analyses, the AAER over 52 weeks was also
assessed in patients grouped by baseline blood eosinophil count,
fractional exhaled nitric oxide (FeNO) level, serum specific
immunoglobin E (IgE) status (perennial allergen sensitivity
positive or negative).8 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 tezepelumab and placebo groups in the NAVIGATOR
trial.8 The
most frequently reported adverse events for tezepelumab were
nasopharyngitis, upper respiratory tract infection and
headache.8
NAVIGATOR is the first Phase III trial to show benefit in severe
asthma irrespective of eosinophils by targeting thymic stromal
lymphopoietin (TSLP).8 These
results 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.
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, 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
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.17
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.20,21 TSLP
is released in response to multiple triggers associated with asthma
exacerbations, including allergens, viruses and other airborne
particles.20,21 Expression
of TSLP is increased in the airways of patients with asthma and has
been correlated with disease severity.20,22 Blocking
TSLP may prevent the release of pro-inflammatory cytokines by
immune cells, resulting in the prevention of asthma exacerbations
and improved asthma control.20,22 Tezepelumab
acts at the top of the inflammation cascade and has the potential
to help address a broad population of severe asthma patients
regardless of their type of inflammation.20,22
Amgen collaboration
In 2020, Amgen and AstraZeneca updated a 2012 collaboration
agreement for tezepelumab.
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 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, part of BioPharmaceuticals, is one of
AstraZeneca's three 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 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.
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: June 2021].
2. Wenzel S. Severe Asthma in
Adults. Am J Respir Crit Care
Med. 2005;172;149-60.
3. Peters
SP, et
al. Uncontrolled asthma: a
review of the prevalence, disease burden and options for
treatment. Respir Med. 2006;100:1139-51.
4. 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.
5. 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.
6. Chung
KF, et
al. International ERS/ATS
guidelines on definition, evaluation and treatment of severe
asthma. Eur Respir
J. 2014; 43:
343-73.
7. Fernandes
AG, et
al. Risk factors for death in
patients with severe asthma. J Bras
Pneumol. 2014; 40 (4):
364-372.
8. 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.
9.
The Global Asthma Network. The Global Asthma Report 2018. [Online].
Available at:
http://globalasthmareport.org/Global%20Asthma%20Report%202018.pdf.[Last
accessed: May 2021].
10. 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.
11. 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.
12. 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.
13.
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: April 2021].
14. 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. RespirRes. 2020;21:266.
15. Wechsler
ME, et
al. Oral corticosteroid-sparing
effect of tezepelumab in adults with severe
asthma. Am J Respir Crit Care
Med.
2021;203:A1197.
16. 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.
17.
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: May 2021].
18. Diver S, et al. Effect of Tezepelumab on Airway Inflammation
in Patients with Moderate-to-Severe Uncontrolled Asthma: A Phase 2,
Randomized, Double-Blind, Placebo-Controlled Study
(CASCADE). Am J Respir Crit Care
Med.
2021;203:A1456.
19.
Clinicaltrials.gov. Study to Evaluate Tezepelumab on Airway
Inflammation in Adults With Uncontrolled Asthma (CASCADE).
Available at: https://clinicaltrials.gov/ct2/show/NCT03688074.
[Last accessed: May 2020].
20. Corren J, et al. Tezepelumab in adults with uncontrolled
asthma [supplementary appendix; updated April 18,
2019]. N Engl J
Med.
2017;377:936-946.
21. Varricchi
G, et
al. Thymic Stromal
Lymphopoietin Isoforms, Inflammatory Disorders, and
Cancer. Front
Immunol.
2018;9:1595.
22. 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.
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:
08 July 2021
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|