REG - AstraZeneca PLC - Tezspire recommended for EU approval in asthma

AstraZenecaAnnouncement

25/07/2022 07:16

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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 (https://www.nejm.org/doi/full/10.1056/NEJMoa2034975) 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
(https://www.astrazeneca.com/media-centre/press-releases/2021/tezspire-tezepelumab-approved-in-the-us-for-severe-asthma.html)
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
(https://www.astrazeneca.com/media-centre/press-releases/2021/tezepelumab-granted-fda-priority-review-for-asthma.html)
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
(https://www.astrazeneca.com/media-centre/press-releases/2021/tezepelumab-granted-orphan-drug-designation-in-the-us-for-eosinophilic-esophagitis.html)
by the FDA for the treatment of EoE.

 

Amgen collaboration

In 2020, Amgen and AstraZeneca updated a 2012 collaboration agreement
(https://otp.tools.investis.com/clients/uk/astrazeneca/rns/regulatory-story.aspx?cid=1343&newsid=665331)
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 (http://www.astrazeneca.com) and follow the
Company on Twitter @AstraZeneca (https://twitter.com/AstraZeneca)

 

Contacts

For details on how to contact the Investor Relations Team, please click here
(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
.

 

 

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
(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
(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
(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
(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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