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 has included the pivotal NAVIGATOR phase III trial in which Tezspire has demonstrated superiority across every primary and key secondary endpoint in patients with severe asthma, compared to placebo, when added to standard therapy.
Tezspire is the first 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.
Tezspire has reduced asthma exacerbations across the PATHWAY phase II and the NAVIGATOR phase III clinical trials, which has included a broad population of severe asthma patients irrespective of key biomarkers, including blood eosinophil counts, allergic status and fractional exhaled nitric oxide ( FeNO ).
In clinical trials, the most common adverse events in patients who received Tezspire were pharyngitis, rash, arthralgia and injection site reactions.
Results from the NAVIGATOR phase III trial were published in The New England Journal of Medicine.
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 ( oral corticosteroids ) treatment.
The trial population included approximately equal proportions of patients with high ( 300 or more cells per microlitre ) and low ( less than 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.
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.
As part of prespecified analyses, the annualised asthma exacerbation rate 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 ).
There were no clinically meaningful differences in safety results between the Tezspire and placebo groups in the NAVIGATOR trial. The most frequently reported adverse events for Tezspire were nasopharyngitis, upper respiratory tract infection and headache.
Tezepelumab is 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.
TSLP is released in response to multiple triggers associated with asthma exacerbations, including allergens, viruses and other airborne particles.
Expression of TSLP is increased in the airways of patients with asthma and has been correlated with disease severity. Blocking TSLP may prevent the release of pro-inflammatory cytokines by immune cells, resulting in the prevention of asthma exacerbations and improved asthma control.
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.
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.
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 ).
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.
Up to 10% of asthma patients have severe asthma.
Despite the use of asthma controller medicines, many severe asthma patients remain uncontrolled.
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.
Severe, uncontrolled asthma is debilitating with patients experiencing frequent exacerbations, significant limitations on lung function and a reduced quality of life.
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. ( Xagena )
Source: AstraZeneca, 2022