Tezepelumab by AstraZeneca and Amgen Significantly Reduces Exacerbations Across a Broad Population of Severe, Uncontrolled Asthma Patients

May 16, 2021 /BioonBIOON/ -- Amgen and its partnersAstraZeneca(AstraZeneca) recently at the American Thoracic Society (ATS) 2021 InternationalMeetingDetailed data from the pivotal Phase 3 NAVIGATOR trial of the antibody drug tezepelumab for the treatment of severe asthma were published. The results confirmed: in a broad population of severe uncontrolledAsthmaAmong patients, compared with the placebo + standard of care (SoC) regimen,Tezepelumab + SoC demonstrated superiority across all primary and key secondary endpoints.. These results have been simultaneously published in the international medical journal *The New England Journal of Medicine* (NEJM), entitled:Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma。

Tezepelumab, co-developed by Amgen and AstraZeneca, is a potential first-in-class drug that blocks the activity of thymic stromal lymphopoietin (TSLP), an epithelial cytokine involved inAsthmaplays a key role in inflammation.

Currently, a marketing application for tezepelumab for the treatment of severe asthma has been submitted in the United States. It is worth noting that,tezepelumab is the first in a broad range of severeAsthmaA Biologic That Provides Sustained and Significant Reduction in Exacerbations Across the Patient Population, Regardless of Baseline Eosinophil Levels. In 2018, the United StatesFDATezepelumab was granted Breakthrough Therapy Designation (BTD).

Asthma

In a pre-specified exploratory analysis of the NAVIGATOR study, based on blood eosinophil counts and fractional exhaled nitric oxide (FeNO) levels,Across all 4 patient subgroups, compared with placebo + SoC, tezepelumab + SoC treatment over the 52-week periodAsthmaReduction in Annualized Exacerbation Rate (AAER). Blood eosinophil count and FeNO levels are two key inflammatoryBiomarker, defined as: blood eosinophil count (≥300 or <300 cells/μL) and FeNO (≥25 or <25 ppb).

In patients with elevated baseline blood eosinophil counts (≥300 cells/μL) and elevated FeNO levels (≥25 ppb), treatment with tezepelumab + SoC resulted in a clinically meaningful 77% reduction in AAER compared with placebo + SoC. In a separate exploratory analysis, compared with placebo + SoC,Tezepelumab + SoC reduced exacerbations requiring hospitalization by 85% over a 52-week period.

Data for 4 Subgroups (Click Image to View Enlarged Version)

Compared with placebo + SoC, tezepelumab + SoC treatment at the key secondary endpoint of lung function,AsthmaThere were also statistically significant improvements in disease control and health-related quality of life. In patients receiving tezepelumab + SoC, improvements were observed as early as Week 2 of treatment or at the first assessment timepoint, and were sustained throughout the treatment period.。

These results build upon data from the NAVIGATOR study, published in February 2021, which showed that: in the overall patient population, compared with placebo + SoC treatment,Tezepelumab + SoC treatment significantly reduced AAER by 56% over 52 weeks.、The difference was statistically and clinically significant (AAER: 0.93 vs. 2.10; RR = 0.44; p < 0.001). Regardless of blood eosinophil count, allergic status, or FeNO levels, the AAER was significantly lower in patients treated with tezepelumab compared with placebo.

Primary endpoint data

Professor Andrew Menzies-Gow, Principal Investigator of the NAVIGATOR study and Director of Respiratory Medicine at the Royal Brompton Hospital in the UK, stated: "Treating severe asthma is a significant challenge, as multiple inflammatory pathways often contribute to the complexity of the disease in patients. These latest results,emphasized tezepelumab for a broad spectrum of severeAsthmaTransformative Potential of Treatment for Patients (Regardless of Inflammatory Type)。”

David M. Reese, Executive Vice President of Research & Development at Amgen, said: “Severe, uncontrolled asthma is debilitating, and patients frequently experience exacerbations that lead to hospitalizations. Therefore, we are very pleased to see that patients treated with tezepelumab during the trial experienced reductions in both emergency department visits and hospitalizations. For over 20 years, Amgen’s inflammation research has been a driving force behind advancing science to address such unmet patient needs. Together with our partner AstraZeneca, we are enthusiastic about these results and tezepelumab’s potential for the broader”Asthmafeel incredibly proud of the patients' potential.”

Mechanism of Action of Tezepelumab (Image sourced from literature PMID: 33050900)

TSLP is an epithelial cytokine produced in response to pro-inflammatory stimuli (such as pulmonary allergens, viruses, and other pathogens) and plays a critical role in the initiation and persistence of airway inflammation. TSLP drives the release of downstream type 2 (T2) cytokines, including IL-4, IL-5, and IL-13, leading to inflammation and asthma symptoms. TSLP can also activate various cell types involved in non-T2-driven inflammation. Therefore, the early upstream activity of TSLP in the inflammatory cascade has been identified as a potential target across a broad asthma patient population. Blocking TSLP prevents immune cells from releasing pro-inflammatory cytokines, thereby preventing asthma exacerbations and improvingAsthmaControl.

Tezepelumab is a first-in-class anti-TSLP monoclonal antibody that specifically binds to human TSLP and blocks its interaction with the receptor complex, thereby preventing TSLP-targeted immune cells from releasing pro-inflammatory cytokines, which prevents asthma exacerbations and improves asthma control. Due to its action early upstream in the inflammatory cascade, tezepelumab may be suitable for a broad range of severe uncontrolledAsthmaPatients, regardless of patient phenotype or T2BiomarkerStatus.

Severe asthma is a debilitating disease affecting approximately 34 million people worldwide. Due to the complexity of severe asthma, despite receiving standard-of-care inhaled medications, currently available biologic therapies, and oral corticosteroids (OCS), many severeAsthmaPatients will continue to experience symptoms and frequent exacerbations.

The mechanism of action of tezepelumab differs from that of any other asthma biologic; it targets multiple inflammatory pathways that drive asthma symptoms and exacerbations. Tezepelumab has the potential to transform the currently underserved broad population of severeAsthmaCare for the patient population, including those without an eosinophilic phenotype.

Currently, tezepelumab is being jointly developed by AstraZeneca and Amgen. Industry analysts believe that if tezepelumab successfully reaches the market, it willAsthmatrigger a major disruption in the therapeutic landscape, with its target patient population far exceeding that of currently marketed biologics, includingGlaxoSmithKline(GSK)'s Nucala (mepolizumab, targeting IL-5), Teva's Cinqair (reslizumab, targeting IL-5), and biologics currently under development for the treatment of asthma, such as AstraZeneca's own benralizumab (targeting the IL-5 receptor α subunit [IL-5Rα]) and Sanofi's Dupixent (targeting IL-4/IL-13), all four of these therapies target only specific inflammatory molecules that drive asthma inflammation and are only suitable for certain types of patients with severe asthma, namely subgroup patients, such as eosinophilicAsthma.(Bioon.com)

Original Source: New Tezepelumab Data Continue To Strengthen Profile For A Broad Population Of Severe Asthma Patients