RNS Number : 6973A
27 September 2022
27 September 2022 07:00 BST
Tezspire approved in Japan for the treatment of severe
Tezspire approved for a broad population of patients with severe
asthma with no phenotype or biomarker limitations
AstraZeneca's Tezspire (tezepelumab) has been approved in Japan
for the treatment of bronchial asthma in patients with severe or
refractory disease in whom asthma symptoms cannot be controlled
with mid- or high-dose inhaled corticosteroids and other long-term
The approval by the Japanese Ministry of Health, Labour and
Welfare (MHLW) was based on efficacy and safety 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 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 .(2-5)
Tezspire consistently and significantly reduced asthma
exacerbations across the PATHWAY Phase II and 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
Hironori Sagara, Professor and Chairman of the Department of
Medicine Division of Respiratory Medicine & Allergology, Showa
University School of Medicine, Tokyo, Japan, said: "Severe asthma
is a debilitating disease, and many patients continue to experience
frequent exacerbations and a significantly reduced quality of life
despite recent advances in treatment. Across clinical trials,
Tezspire has demonstrated significant results in a broad population
of severe asthma patients, and with this approval, physicians can
now offer patients in Japan a meaningful new treatment option.
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, AstraZeneca, said: "Tezspire is the first and only
biologic approved by the Japanese Ministry of Health, Labour and
Welfare that has been shown to consistently and significantly
reduce attacks in exacerbation trials in a broad population of
severe asthma patients irrespective of biomarker levels. Tezspire
has the potential to improve outcomes for many patients with severe
asthma and we are working to make this important medicine available
in Japan as quickly as possible ."
In clinical studies, the most common adverse reactions in
patients who received Tezspire were pharyngitis, arthralgia, rash
and injection site reactions.(1) The results from the NOZOMI Phase
III long-term safety trial of Tezspire in Japanese patients were
published in The Journal of Asthma in June 2022.
Results from the NAVIGATOR Phase III trial were published in The
New England Journal of Medicine in May 2021.
Tezspire is approved in the US, the EU and other countries for
the treatment of severe asthma. Other regulatory reviews evaluating
Tezspire are ongoing in several markets around the world.
Asthma is a heterogeneous disease affecting an estimated 339
million people worldwide.(6) Up to 10% of asthma patients have
severe asthma.(7,8) Despite the use of inhaled asthma controller
medicine, currently available biologic therapies and oral
corticosteroids (OCS), many severe asthma patients remain
uncontrolled.(7-9) 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
Severe, uncontrolled asthma is debilitating with patients
experiencing frequent exacerbations, significant limitations on
lung function and a reduced quality of life.(7,8,12) 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.(13-15) There is also a significant
socio-economic burden, with these patients accounting for
approximately 50% of asthma-related costs.(16)
In addition to the Phase IIb PATHWAY trial, the PATHFINDER
programme included two Phase III trials, NAVIGATOR(2,17) and
SOURCE.(18,19) The programme also includes additional mechanistic
and long-term safety trials.(20,21)
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
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.(22)
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.(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 approved in the US for the add-on maintenance
treatment of adult and paediatric patients aged 12 years and older
with severe asthma.(27) 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.
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
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 (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
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1. Tezspire (tezepelumab) Japan prescribing information; 2022.
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 Immunol. 2018; 9:
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. 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].
7. Chung KF, et al . International ERS/ATS guidelines on
definition, evaluation and treatment of severe asthma. Eur Respir J
. 2014; 43 (2): 343-373.
8. Wenzel S. Severe asthma in adults. Am J Respir Crit Care Med . 2005; 172: 149-160.
9. Peters SP, et al . Uncontrolled asthma: a review of the
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10. 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.
11. 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.
12. Fernandes AG, et al. Risk factors for death in patients with
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13. 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.
14. 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:
15. 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:
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asthma: economic analysis of the cost of treatments for severe
asthma. Available at:
[Last accessed: December 2021].
17. 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:
18. Wechsler ME, et al. Oral corticosteroid-sparing effect of
tezepelumab in adults with severe asthma. Am J Respir Crit Care
Med. 2021;203: A1197.
19. 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.
20. 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:
21. 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. Available at: https://doi.org/10.1016/S2213-2600(21)00226-5.
[Last accessed December 2021].
22. Tezspire (tezepelumab) US prescribing information; 2021.
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