Report of Foreign Issuer Pursuant to Rule 13a-16 or 15d-16 (6-k)

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 September 2022

Commission File Number: 001-11960

AstraZeneca PLC

1 Francis Crick Avenue

Cambridge Biomedical Campus

Cambridge CB2 0AA

United Kingdom

Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F.

Form 20-F X Form 40-F __

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(1):

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(7): ______

Indicate by check mark whether the registrant by furnishing the information contained in this Form is also thereby furnishing the information to the Commission pursuant to Rule 12g3-2(b) under the Securities Exchange Act of 1934.

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If “Yes” is marked, indicate below the file number assigned to the Registrant in connection with Rule 12g3-2(b): 82-_____________

AstraZeneca PLC

INDEX TO EXHIBITS

Tezspire approved in the EU for severe asthma

21 September 2022 07:00 BST

Tezspire approved in the EU for the treatment of severe asthma

First and only biologic approved in the EU in patients with severe asthma with no phenotype or biomarker limitations

AstraZeneca's Tezspire (tezepelumab) has been approved in the European Union (EU) as an add-on maintenance treatment in patients 12 years and older with severe asthma who are inadequately controlled with high dose inhaled corticosteroids plus another medicinal product.

The approval by the European Commission was based on results from the PATHFINDER clinical trial programme, which included 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 The approval follows the recommendation by The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency in July 2022.

Tezspire is the first and only biologic approved in Europe 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 the PATHWAY Phase II and the 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 (FeNO).1,2

Professor Guy Brusselle, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium, said: "Severe asthma is a complex disease given approximately 60% of patients have multiple drivers of inflammation. With the European approval of Tezspire, a first-in-class biologic acting at the top of the inflammation cascade, we have an opportunity to treat a broader population of patients with severe asthma, fulfilling a high unmet need in this disease."

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: "Severe asthma continues to have a debilitating impact for people living with the disease, with many patients experiencing frequent exacerbations, an increased risk of hospitalisation and a significantly reduced quality of life. Tezspire is now the first and only biologic approved in Europe for patients with severe asthma with no phenotype or biomarker limitation and we look forward to bringing this important medicine to patients as quickly as possible."

In clinical trials, the most common adverse events in patients who received Tezspire were pharyngitis, rash, arthralgia and injection site reactions.5

Results from the NAVIGATOR Phase III trial were published in The New England Journal of Medicine in May 2021.

Tezspire has been approved in the US and other countries for the treatment of severe asthma, and regulatory reviews are ongoing in additional 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, NAVIGATOR1,19 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.

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.5 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 (112): 105-12.

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 (2): 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 (7): 1139-51.

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: 467-73.

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

21. 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.

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 (11): 1299-1312.

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.

AstraZeneca PLC

Date: 21 September 2022