Monoclonal Antibody Proves Worth in Asthma Study

Asthma

 

Pivotal data from Amgen’s and AstraZeneca’s NAVIGATOR Phase III trial show tezepelumab, a potential first-in-class human monoclonal antibody, reduced asthma aggravations and exacerbations requiring hospitalizations better than placebo in patients with severe asthma. 

Based on these positive findings, the two companies have submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for tezepelumab in severe asthma. 

In the NAVIGATOR trial, a total of 1,061 patients with severe, uncontrolled asthma were randomly assigned to receive either tezepelumab plus standard of care or placebo and standard of care for 52 weeks. All patients were previously and currently receiving treatment with a medium- or high-dose inhaled corticosteroid plus one or more additional controller medications with or without oral corticosteroids (OCS).

The findings from this trial were recently published in the New England Journal of Medicine, ahead of being presented this week at the American Thoracic Society (ATS) 2021 International Conference. 

The new data published in the NEJM are based on a subgroup analysis of patients with elevated inflammatory biomarkers, including elevated blood eosinophil counts and fractional exhaled nitric oxide (FeNO) levels. Clinicians use these two vital inflammatory biomarkers to guide treatment decision making in patients with severe asthma. 

Treatment with tezepelumab in the NAVIGATOR trial led to a 77% reduction in the annualized asthma exacerbation rate compared with placebo in patients with elevated blood eosinophil counts and elevated FeNO levels at baseline. In addition, a separate exploratory analysis found tezepelumab led to an 85% reduction in exacerbations requiring hospitalizations over the 52-week treatment period compared with placebo. 

Patients who received tezepelumab and standard of care also had significant improvements compared with placebo in their lung function, asthma control, and health-related quality of life. These improvements in the tezepelumab arm were observed as early as two weeks into treatment and were sustained throughout the 52 weeks. 

"These latest results underscore the potential of tezepelumab to transform treatment for a broad population of severe asthma patients regardless of their type of inflammation," according to a statement made by principal NAVIGATOR trial investigator, Professor Andrew Menzies-Gow, Director of the Lung Division, Royal Brompton Hospital in London, UK.

Data presented in February showed that treatment with tezepelumab resulted in statistically significant and clinically meaningful reductions in the annualized asthma exacerbation rate over 52 weeks in the overall study population. 

Findings from a primary analysis of another tezepelumab trial from Amgen and AstraZeneca, the Phase III SOURCE study, will also be presented at the ATS conference this week. 

In this study, patients who received tezepelumab experienced improvements in exacerbations forced expiratory volume in one second and patient-reported outcomes compared with the placebo arm. This trial did not meet the primary endpoint of a significant reduction in the daily OCS; however, a higher proportion of patients treated with tezepelumab in this study experienced a 90% or more reduction in their OCS dose and those treated with placebo.

Additional findings from the PATHFINDER clinical trial program, will also be presented at this week’s ATS conference, which includes data from SOURCE as well as the Phase II CASCADE trial. 

In CASCADE, treatment with tezepelumab reduced eosinophils in the airway tissue of patients with moderate to severe asthma compared with placebo. Additionally, the active treatment seemingly reduced airway hyperresponsiveness better than placebo. 

Data from the three phase three studies have been compiled into the BLA submission for tezepelumab submitted to the FDA on Monday.

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