AstraZeneca and Amgen have announced positive results from the NAVIGATOR Phase III trial for a potential new medicine that could help patients with severe, uncontrolled asthma.
Severe asthma is a debilitating condition affecting approximately 34 million people worldwide. Many severe asthma patients continue to experience symptoms and frequent exacerbations despite the use of high-dose asthma controller medicines, currently available biologic therapies, and oral corticosteroids.
NAVIGATOR met the primary endpoint with the potential new medicine tezepelumab added to standard of care – demonstrating a statistically significant and clinically meaningful reduction in the annualised asthma exacerbation rate over 52 weeks in the overall patient population, compared to placebo when added to standard of care. Standard of care was medium- or high-dose inhaled corticosteroids plus at least one additional controller medication with or without oral corticosteroids.
Reduction in annualised asthma exacerbation rate
Severe, uncontrolled asthma is debilitating, and patients who live with the condition experience frequent exacerbations, significant limitations on lung function, and a reduced quality of life. They are also at an increased risk of mortality and account for twice as many asthma-related hospitalisations, and there is a significant socio-economic burden, with these patients accounting for 50% of asthma-related costs.
For the subgroup of patients with baseline eosinophil (a variety of white blood cell) counts of less than 300 cells per microlitre the trial also met the primary endpoint, with tezepelumab demonstrating a statistically significant and clinically meaningful reduction in the annualised asthma exacerbation rate. Similar reductions in the annualised asthma exacerbation rate were observed in the subgroup of patients with baseline eosinophil counts less than 150 cells per microlitre.
The findings demonstrated that tezepelumab, a potential first-in-class medicine that blocks the action of thymic stromal lymphopoietin (TSLP), an epithelial cytokine that plays a key role across the spectrum of asthma inflammation, was very well tolerated in patients with severe asthma. The preliminary analyses show no clinically meaningful differences in safety results between the tezepelumab and placebo groups.
Professor Andrew Menzies-Gow, Director of the Lung Division, Royal Brompton Hospital, London, UK, and principal investigator of the NAVIGATOR Phase III trial, said: “Due to the complex nature of severe asthma, many patients continue to face debilitating symptoms despite receiving standard of care inhaled medicines and currently approved biologics. Today’s ground-breaking results show that tezepelumab has the potential to transform care for a broad population of severe asthma patients who are underserved today, including those without an eosinophilic phenotype.”
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “Tezepelumab works differently from any other asthma biologic medicine and targets multiple inflammatory pathways that contribute to asthma symptoms and exacerbations. Building on the broad efficacy previously seen with tezepelumab, these are exciting data that bring us one step closer to delivering a medicine to severe asthma patients, including those with low eosinophil counts.”
The findings from the trial support the US Food and Drug Administration Breakthrough Therapy Designation granted to tezepelumab in September 2018 for patients with severe asthma, without an eosinophilic phenotype.