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,
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.
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 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.
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.
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