AstraZeneca has reported positive full results from the pivotal Phase III NAVIGATOR trial of human monoclonal antibody tezepelumab which showed reduction in exacerbation rate in severe, uncontrolled asthma patients.
Developed by AstraZeneca in partnership with Amgen, tezepelumab is a potential first-in-class antibody that hinders thymic stromal lymphopoietin (TSLP) action.
The randomised, double-blinded, placebo-controlled trial had adolescents and adults with severe, uncontrolled asthma. They were receiving medium or high-dose inhaled corticosteroids plus at least one additional controller medication, with or without oral corticosteroids.
With a screening period of five to six weeks, the trial had a treatment period of 52 weeks. The participants were followed up for 12 weeks after receiving treatment.
The annualised asthma exacerbation rate (AAER) during the treatment period formed the trial’s primary efficacy endpoint.
According to the results, tezepelumab showed a statistically significant and clinically meaningful reduction in AAER in severe, uncontrolled asthma patients.
In addition, tezepelumab plus standard of care (SoC) achieved a 56% reduction in AAER over 52 weeks in the overall patient population, versus placebo plus SoC.
Data from pre-planned subgroup analysis showed that tezepelumab achieved a statistically significant and clinically meaningful 41% reduction in AAER in patients with baseline eosinophil counts below 300 cells per microlitre.
The antibody also showed significant improvements in every key secondary endpoint, including lung function measurements, asthma control and health-related quality of life versus placebo.
AstraZeneca noted that tezepelumab is the only biologic treatment to consistently and significantly lower AAER in a wide population of severe asthma patients regardless of baseline eosinophil count across Phase II and Phase III trials.
AstraZeneca BioPharmaceuticals R&D executive vice-president Mene Pangalos said: “The unprecedented results from the NAVIGATOR Phase III trial show tezepelumab is the first and only asthma biologic to demonstrate in randomised trials clinically meaningful exacerbation reductions, irrespective of blood eosinophil counts, allergy status and fractional exhaled nitric oxide.”