REG - AstraZeneca PLC - Tezspire approved in the US for severe asthma

AstraZenecaAnnouncement

20/12/2021 07:05

For best results when printing this announcement, please click on link below:
http://newsfile.refinitiv.com/getnewsfile/v1/story?guid=urn:newsml:reuters.com:20211220:nRST1205Wa&default-theme=true

RNS Number : 1205W  AstraZeneca PLC  20 December 2021

20 December 2021 07:05 GMT

 

Tezspire (tezepelumab) approved in the US for severe asthma

 

First and only biologic to consistently and significantly reduce exacerbations in a broad population of severe asthma patients
 
Only biologic for severe asthma approved with no phenotype or biomarker limitations
 

AstraZeneca and Amgen's Tezspire (tezepelumab-ekko) has been approved in the
US for the add-on maintenance treatment of adult and paediatric patients aged
12 years and older with severe asthma.(1)

 

Tezspire was approved following a Priority Review
(https://www.astrazeneca.com/media-centre/press-releases/2021/tezepelumab-granted-fda-priority-review-for-asthma.html)
by the US Food and Drug Administration (FDA) and based on 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 a first-in-class biologic for severe asthma that acts at the top
of the inflammatory cascade by targeting thymic stromal lymphopoietin (TSLP),
an epithelial cytokine.(2-5) It is the first and only biologic to consistently
and significantly reduce 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).(2,3,6-13) Tezspire is the
only biologic approved for severe asthma with no phenotype (e.g. eosinophilic
or allergic) or biomarker limitation within its approved label.(1)

 

Professor Andrew Menzies-Gow, Director of the Lung Division, Royal Brompton
Hospital, London, UK, and principal investigator of the NAVIGATOR trial, said:
"Due to the complex and heterogeneous nature of severe asthma and despite
recent advances, many patients continue to experience frequent exacerbations,
an increased risk of hospitalisation and a significantly reduced quality of
life. Tezspire represents a much-needed new treatment for the many patients
who remain underserved and continue to struggle with severe, uncontrolled
asthma."

 

Tonya Winders, President and CEO of Allergy & Asthma Network, and
President of the Global Allergy and Airways Patient Platform, said: "Severe
asthma continues to have a debilitating impact on many of the 34 million
people living with the disease worldwide, affecting their breathing and
limiting aspects of day-to-day life. The approval of Tezspire is long-awaited
positive news for the asthma community. For the first time, many people living
with severe asthma have the opportunity to receive treatment regardless of the
cause of their inflammation."

 

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D,
AstraZeneca, said: "Today's positive decision marks the first time the FDA has
approved a biologic for asthma without phenotypic limitation and irrespective
of biomarker levels. With the approval of Tezspire, physicians will now be
able to offer an important new treatment that has the potential to transform
care for a broad population of severe asthma patients."

 

In clinical studies, the most common adverse reactions in patients who
received Tezspire were pharyngitis, arthralgia and back pain.(1)

 

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.(2)

( )

The application for Tezspire was granted Priority Review, a designation given
to applications for medicines that offer significant advantages over available
options by demonstrating safety or efficacy improvements, preventing serious
conditions, or enhancing patient compliance.(14)

 

Tezspire is under regulatory review in the EU, Japan and several other
countries around the world.

 

Notes

 

Severe asthma

Asthma is a heterogeneous disease affecting an estimated 339 million people
worldwide.(15,16) Approximately 10% of asthma patients have severe
asthma.(16,17) Despite the use of inhaled asthma controller medicine,
currently available biologic therapies and oral corticosteroids (OCS), many
severe asthma patients remain uncontrolled.(16-18) 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.(17-20)

 

Severe, uncontrolled asthma is debilitating with patients experiencing
frequent exacerbations, significant limitations on lung function and a reduced
quality of life.(16,17,21) 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.(22-24) There is also a
significant socio-economic burden, with these patients accounting for
approximately 50% of asthma-related costs.(25)

 

Clinical trials

In addition to the Phase IIb PATHWAY trial, the PATHFINDER programme included
two Phase III trials, NAVIGATOR(2,26) and SOURCE.(27,28) The programme also
includes additional mechanistic and long-term safety trials.(29,30)

 

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 headache.(2)

 

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
(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.(29)

 

Tezspire

Tezspire (tezepelumab) is being developed by AstraZeneca in collaboration with
Amgen as 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, 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 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
(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 commercialize 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 chronic
obstructive pulmonary disease (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.   Tezspire (tezepelumab) US prescribing information; 2021.

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: 1595.

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.   Hanania NA, et al. Omalizumab in severe allergic asthma inadequately
controlled with standard therapy: a randomized trial. Ann Intern Med. 2011;154
(9): 573-82.

7.   Yancey SW, et al. Disease burden and efficacy of mepolizumab in
patients with severe asthma and blood eosinophil counts of
≥150-300 cells/μL. Respir Med. 2019; 151: 139-141.

8.   FitzGerald JM, et al. Predictors of enhanced response with benralizumab
for patients with severe asthma: pooled analysis of the SIROCCO and CALIMA
studies. Lancet Respir Med. 2018; 6 (1): 51-64.

9.   Castro M, et al. Dupilumab Efficacy and Safety in Moderate-to-Severe
Uncontrolled Asthma. N Engl J Med. 2018; 378 (26): 2486-2496.

10.  Ortega HG, et al; on behalf of the MENSA Investigators. Mepolizumab
treatment in patients with severe eosinophilic asthma. N Engl J Med.
2014;371(13):1198-207.

11.  Bleecker ER, et al, on behalf of the SIROCCO study investigators.
Efficacy and safety of benralizumab for patients with severe asthma
uncontrolled with high-dosage inhaled corticosteroids and long-acting
beta2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase
3 trial. Lancet 2016: 388 (10056): 2115-2127.

12.  FitzGerald JM, et al, on behalf of the CALIMA study investigators.
Benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, as
add-on treatment for patients with severe, uncontrolled, eosinophilic asthma
(CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial.
Lancet. 2016: 388(10056): 2128-2141.

13.  Wenzel S, et al. Dupilumab efficacy and safety in adults with
uncontrolled persistent asthma despite use of medium-to-high-dose inhaled
corticosteroids plus a long-acting β2 agonist: a randomised double-blind
placebo-controlled pivotal phase 2b dose-ranging trial. Lancet. 2016 Jul
2;388(10039):31-44.

14.  US Food and Drug Administration. Priority Review. Available at:
https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review
(https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review)
. [Last accessed: December 2021].

15.  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: December 2021].

16.  Chung KF, et al. International ERS/ATS guidelines on definition,
evaluation and treatment of severe asthma. Eur Respir J. 2014; 43 (2):
343-373.

17.  Wenzel S. Severe asthma in adults. Am J Respir Crit Care Med. 2005; 172:
149-160.

18.  Peters SP, et al. Uncontrolled asthma: a review of the prevalence,
disease burden and options for treatment. Respir Med 2006: 100 (7): 1139-51.

19.  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.

20.  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.

21.  Fernandes AG, et al. Risk factors for death in patients with severe
asthma. J Bras Pneumol. 2014; 40: 364-372.

22.  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.

23.  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.

24.  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.

25.  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: December 2021].

26.  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.

27.  Wechsler ME, et al. Oral corticosteroid-sparing effect of tezepelumab
in adults with severe asthma. Am J Respir Crit Care Med. 2021;203: A1197.

28.  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.

29.  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: December
2021].

30.  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].

 

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

 

This information is provided by RNS, the news service of the London Stock Exchange. RNS is approved by the Financial Conduct Authority to act as a Primary Information Provider in the United Kingdom. Terms and conditions relating to the use and distribution of this information may apply. For further information, please contact
rns@lseg.com (mailto:rns@lseg.com)
 or visit
www.rns.com (http://www.rns.com/)
.

RNS may use your IP address to confirm compliance with the terms and conditions, to analyse how you engage with the information contained in this communication, and to share such analysis on an anonymised basis with others as part of our commercial services. For further information about how RNS and the London Stock Exchange use the personal data you provide us, please see our
Privacy Policy (https://www.lseg.com/privacy-and-cookie-policy)
.   END  MSCTLBBTMTJBTAB