New administration option for first and only severe asthma biologic approved in the EU with no phenotype or biomarker limitations.

AstraZeneca’s Tezspire (tezepelumab) has received a positive opinion from the European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP) for self-administration in a pre-filled, single-use pen for patients aged 12 years and older with severe asthma. The CHMP opinion can be implemented without the need for a European Commission decision due to the nature of the Type-II label variation.

The approval for self-administration was based on results from the PATHFINDER clinical trial programme, which included results from the PATH-BRIDGE Phase I trial and the PATH-HOME Phase III trial.^1,2 The majority (92%) of healthcare providers, patients and caregivers were able to successfully administer Tezspire both in the clinic and at home throughout the PATH-HOME trial.² The improvements in asthma control and the safety profile of Tezspire observed in the PATH-HOME trial were consistent with previous clinical trials.² Tezspire is the only biologic approved for severe asthma with no phenotype (e.g. eosinophilic or allergic) or biomarker limitation within its approved label.³

Professor Ian Pavord, Professor of Respiratory Medicine at the University of Oxford and Honorary Consultant Physician at the Oxford University Hospitals, said: “Severe asthma continues to have a debilitating impact for people living with the disease. I believe the approval of the Tezspire pre-filled pen will be welcome news for physicians and patients in Europe as it offers increased choice and greater flexibility when administering this important medicine.”

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “Tezspire is the first and only biologic approved in Europe for patients with severe asthma with no phenotype or biomarker limitation. With the approval of the Tezspire pre-filled pen, we can give patients in Europe greater flexibility and support physicians in treating a broad population of severe asthma patients.”

AstraZeneca anticipates a regulatory decision by the US Food and Drug Administration (FDA) on self-administration and the new pre-filled pen in the first half of 2023. Tezspire is currently approved for the treatment of severe asthma in the US, EU, Japan and other countries.^4-6

Notes

Tezspire pre-filled pen
Tezspire will be available as a fixed-dose 210mg subcutaneous injection via a pre-filled, single-use auto-injector (the Tezspire pre-filled pen), in addition to the pre-filled, single-use syringe (Tezspire pre-filled syringe). Both are administered every four weeks.

The Tezspire pre-filled pen enables patients and caregivers to self-administer the medicine at home or in clinic via a simple process. The device is fitted with a safety guard and viewing window and has audible clicks at the start and end of the injection to guide patients.

Clinical trials
PATH-HOME was a Phase III multi-centre, open-label, parallel-group trial designed to assess patient, caregiver and healthcare provider-reported functionality and performance of a single-use, pre-filled syringe (PFS) or auto-injector (AI) with a fixed 210mg dose of Tezspire administered subcutaneously every four weeks in a clinic and in an at-home setting in 216 patients aged 12 years and older with severe asthma.²

The majority (92%) of healthcare providers, patients and caregivers were able to successfully administer the Tezspire pre-filled pen both in the clinic and at home throughout the trial.² At-home administration of the Tezspire pre-filled pen at weeks 12 and 16 was successful in 97% of the patients or caregivers (102/105).² The trial also demonstrated for the first time that adolescents can successfully administer Tezspire using the two devices.² The very low proportion of device malfunctions (0.9% of PFS and 0.8% of AIs) provides support that the instructions for use provided to healthcare providers, patients and caregivers is adequate for successful subcutaneous administration of Tezspire both in the clinic and at home.² 

PATH-BRIDGE was a single-centre, randomised, open-label, parallel-group Phase I trial in healthy people to compare the pharmacokinetic (PK) exposure following a single 210mg dose of Tezspire by using a vial-and-syringe (V-S), PFS or pre-filled AI device.¹ Tezspire PK exposure was comparable following subcutaneous administration via V-S, PFS or AI.¹ In addition, injection site-pain was low in severity and injection-site reactions were uncommon in all device groups.¹

In addition to PATH-BRIDGE and PATH-HOME, the PATHFINDER clinical trial programme 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.⁷

NAVIGATOR was the first Phase III trial to show benefit in severe asthma irrespective of eosinophils by targeting thymic stromal lymphopoietin (TSLP).⁷ 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.^8,9 TSLP is released in response to multiple triggers associated with asthma exacerbations, including allergens, viruses and other airborne particles.^8,9 Expression of TSLP is increased in the airways of patients with asthma and has been correlated with disease severity.^8,9 Blocking TSLP may prevent the release of pro-inflammatory cytokines by immune cells, resulting in the prevention of asthma exacerbations and improved asthma control.^7,8,10 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.^7,8

Tezspire is approved in the US, EU, Japan and other countries for the treatment of severe asthma.^4-6 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.

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References

1. Zheng Y, et al. Tezepelumab Pharmacokinetics, Safety, and Tolerability After Administration via Vial-and-syringe, Accessorized Prefilled Syringe, or Autoinjector: A Randomized Trial in Healthy Volunteers. Clin Thera. 2020;43(1):142-155.
2. Alpizar S, et al. Functionality and Performance of an Accessorized Pre-Filled Syringe and an Autoinjector for At-Home Administration of Tezepelumab in Patients with Severe, Uncontrolled Asthma. J. Asthma Allergy. 2021;14:381-392.
3. European Medicines Agency. Tezspire (tezepelumab) Summary of Product Characteristics (SmPC). Available at: https://www.ema.europa.eu/en/documents/product-information/tezspire-epar-product-information_en.pdf [Last accessed: January 2023].
4. AstraZeneca plc. Tezspire (tezepelumab) approved in the US for severe asthma. Available at: https://www.astrazeneca.com/media-centre/press-releases/2021/Tezspire-tezepelumab-approved-in-the-us-for-severe-asthma.html. [Last accessed: January 2023].
5. AstraZeneca plc. Tezspire approved in the EU for the treatment of severe asthma. 2022. Available at: https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2022/tezspire-approved-in-the-eu-for-the-treatment-of-severe-asthma.html. [Last accessed: January 2023].
6. AstraZeneca plc. Tezspire approved in Japan for the treatment of severe asthma. Available at: https://www.astrazeneca.com/media-centre/press-releases/2022/tezspire-approved-in-japan-for-severe-asthma.html. [Last accessed: January 2023].
7. 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.
8. Corren J, et al. Tezepelumab in adults with uncontrolled asthma [supplementary appendix; updated April 18, 2019]. N Engl J Med. 2017;377:936-946.
9. Varricchi G, et al. Thymic Stromal Lymphopoietin Isoforms, Inflammatory Disorders, and Cancer. Front Immunol. 2018;9:1595.
10. 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.