New Tezepelumab Data Continue to Strengthen Profile for a Broad Population of Severe Asthma Patients

Detailed results from the pivotal NAVIGATOR Phase III trial showed AstraZeneca and Amgen’s tezepelumab, a potential first-in-class treatment, demonstrated superiority across every primary and key secondary endpoint in a broad population of severe asthma patients, compared to placebo when added to standard of care (SoC).

In one of the pre-specified exploratory analyses of NAVIGATOR, reductions in annualized asthma exacerbation rates (AAERs) were observed over 52 weeks in tezepelumab-treated patients compared to placebo when added to SoC across four patient subgroups, based on blood eosinophil count and fractional exhaled nitric oxide (FeNO) levels. Blood eosinophil counts and FeNO levels are two key inflammatory biomarkers used by clinicians to inform treatment options and were defined as blood eosinophil count (≥300 or <300 cells per microliter) and FeNO (≥25 or <25 parts per billion).

In patients with elevated baseline blood eosinophil counts (≥300 cells per microliter) and FeNO levels (≥25 parts per billion), tezepelumab achieved a clinically meaningful 77% reduction in the AAER, compared to placebo.

In a separate exploratory analysis of exacerbations requiring hospitalizations, tezepelumab showed an 85% reduction over 52 weeks compared to placebo when added to SoC.

Tezepelumab also demonstrated statistically significant improvements in key secondary endpoints compared to placebo in lung function, asthma control and health-related quality of life. Improvements were observed in tezepelumab-treated patients as early as week two of treatment or the first time point assessment and were sustained throughout the treatment period.

These results build on the NAVIGATOR data presented in February 2021 which showed a statistically significant and clinically meaningful reduction in the primary endpoint of AAER over 52 weeks in the overall patient population. Clinically meaningful reductions in AAER compared to placebo were observed in the tezepelumab-treated patients irrespective of blood eosinophil counts, allergy status or FeNO level.

Professor Andrew Menzies-Gow, Director of the Lung Division, Royal Brompton Hospital, London, UK, and principal investigator of the NAVIGATOR Phase III trial, said: “Managing severe asthma is challenging, with multiple inflammatory pathways often contributing to the complexity of a patient's disease. 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.”

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “The reduction in hospitalizations seen in NAVIGATOR is important because patients with severe asthma have twice the risk of asthma-related hospitalizations. These results show tezepelumab has the potential to treat a broad population of severe asthma patients and to reduce the burden that this disease places on healthcare systems.”

These results were published in the New England Journal of Medicine and will be presented this week at the American Thoracic Society (ATS) 2021 International Conference.

Further results from the tezepelumab PATHFINDER clinical trial program will also be presented at the ATS Conference this week, including the primary analyses from the SOURCE Phase III and CASCADE Phase II trials.

As previously disclosed, the SOURCE Phase III trial did not meet the primary endpoint of a statistically significant reduction in the daily oral corticosteroid (OCS) dose, without loss of asthma control, with tezepelumab compared to placebo. Data to be presented show the number of patients that achieved a ≥90% reduction in OCS dose was numerically higher for tezepelumab-treated patients at 54.1% compared to 46.1% in the placebo group.

In SOURCE, tezepelumab-treated patients showed improvements in exacerbations, forced expiratory volume in one second and patient-reported outcomes compared to placebo, consistent with improvements shown in pooled post-hoc analyses in OCS dependent patients from the PATHWAY Phase II and NAVIGATOR Phase III trials. New trials are being planned to evaluate the ability of tezepelumab to reduce OCS use while maintaining asthma control in patients with chronic maintenance OCS therapy. Any new trial would aim to address unique aspects of the SOURCE trial design that may have contributed to the result of the primary endpoint.

Also being presented at the ATS Conference, results from the CASCADE Phase II mechanistic trial showed that in a broad population of moderate-to-severe asthma patients, tezepelumab reduced eosinophils in airway tissue, compared to placebo, across subgroups of baseline blood eosinophil count, FeNO level, and allergic status. Importantly, tezepelumab was also associated with a reduction in airway hyper-responsiveness compared to placebo, which is a major hallmark of asthma irrespective of eosinophilic airway inflammation.

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