TIDMAZN
RNS Number : 5249T
AstraZeneca PLC
25 July 2022
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, NAVIGATOR(1,19) 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
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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
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