Amgen (AMGN) Announces New Tezepelumab Data Continue To Strengthen Profile For A Broad Population Of Severe Asthma Patients

Amgen (NASDAQ: AMGN) and AstraZeneca today announced detailed results for tezepelumab, a potential first-in-class treatment, from the pivotal NAVIGATOR Phase 3 trial demonstrating 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). 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.1,2

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 microlitre) and FeNO (≥25 or <25 parts per billion).

In patients with elevated baseline blood eosinophil counts (≥300 cells per microlitre) and FeNO levels (≥25 parts per billion), tezepelumab achieved a clinically meaningful 77% reduction in the AAER, compared to placebo.1,2

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.1

These results build on the NAVIGATOR data presented in February 2021 which showed a statistically significant and clinically meaningful3 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.1

"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," said Professor Andrew Menzies-Gow, Director of the Lung Division, Royal Brompton Hospital, London, UK, and principal investigator of the NAVIGATOR Phase 3 trial.

"Severe, uncontrolled asthma is debilitating, with patients experiencing frequent exacerbations that lead to hospitalization. For this reason, we were incredibly pleased to see that patients who received tezepelumab during the trial had a reduction in both ER visits and hospitalizations," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "Advancing the science to address unmet patient needs such as these has been the driving force behind Amgen's inflammation research for more than two decades. Along with our partner AstraZeneca, we are incredibly proud of these results and tezepelumab's potential for a broad population of patients with asthma."

Additional Data to be Presented

Further results from the tezepelumab PATHFINDER clinical trial program will be presented at the ATS conference this week, including the primary analyses from the SOURCE Phase 3 and CASCADE Phase 2 trials.

As previously disclosed, the SOURCE Phase 3 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.4

In SOURCE, tezepelumab-treated patients showed improvements in exacerbations, forced expiratory volume in one second and patient-reported outcomes compared to placebo,4 consistent with improvements shown in pooled post-hoc analyses in OCS dependent patients from the PATHWAY Phase 2 and NAVIGATOR Phase 3 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 2 mechanistic trial showed that in a broad population of patients with moderate to severe asthma, tezepelumab reduced eosinophils in airway tissue compared to placebo across subgroups of baseline blood eosinophil count, FeNO level and allergic status.5 Importantly, tezepelumab was also associated with a reduction in airway hyper-responsiveness compared to placebo,5 which is a major hallmark of asthma irrespective of eosinophilic airway inflammation.

There were no clinically meaningful differences in safety results between the tezepelumab and placebo groups in NAVIGATOR,1 SOURCE4 and CASCADE.5 The most frequently reported adverse events for tezepelumab in the NAVIGATOR trial were nasopharyngitis, upper respiratory tract infection, headache and asthma,1 in the SOURCE trial were nasopharyngitis, upper respiratory tract infection, asthma, and bronchitis bacterial, and in the CASCADE trial were nasopharyngitis, post-procedural (bronchoscopy) complications and headache.

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