Tezepelumab Treatment Effect on Annualized Rate of Exacerbations by Baseline Biomarkers in Uncontrolled Severe Asthma Patients: Phase 2b PATHWAY Study

Corren, Jonathan; Gil, Esther Garcia; Parnes, Jane R.; Pham, Timothy; Griffiths, José-Marie

doi:10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a2621

Cited by 17 publications

(24 citation statements)

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“…Reductions in exacerbations were seen in patients irrespective of baseline biomarker levels, including blood eosinophil counts and fractional exhaled nitric oxide levels. 13,20,21 Importantly, tezepelumab also improved clinical measures of lung function, asthma control, and HRQoL. 13 In a previous analysis of PATHWAY, patients treated with tezepelumab had greater improvements from baseline in Asthma Control Questionnaire-6 (ACQ-6) and Asthma Quality of Life Questionnaire (standardized) for patients aged 12 years or older (AQLQ[S]+12) scores than those treated with placebo.…”

Section: Introductionmentioning

confidence: 98%

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Tezepelumab improves patient-reported outcomes in patients with severe, uncontrolled asthma in PATHWAY

Corren

Gil

Griffiths

et al. 2021

Annals of Allergy, Asthma & Immunology

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Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Tezepelumab improves patient-reported outcomes in patients with severe, uncontrolled asthma in PATHWAY

Corren

Gil

Griffiths

et al. 2021

Annals of Allergy, Asthma & Immunology

View full text Add to dashboard Cite

show abstract

“…This hypothesis is supported by results from the PATHWAY study, which demonstrated that tezepelumab reduced exacerbations in patients with severe, uncontrolled asthma, irrespective of their baseline inflammation status [28,36]. In a subgroup analysis of the PATHWAY population, reductions in exacerbations were observed in patients with a blood eosinophil count of less than 300 cells/μL [28,36]. NAVIGATOR aims to further assess the efficacy of tezepelumab across a range of severe asthma phenotypes, including patients without an eosinophilic phenotype.…”

Section: Discussionmentioning

confidence: 88%

NAVIGATOR: a phase 3 multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma

et al. 2020

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Background Patients with severe, uncontrolled asthma have a significant unmet need for new treatments that have broader effects on airway inflammation, and that provide greater improvements in asthma outcomes than currently approved biologics and standard-of-care therapies. Tezepelumab is a human monoclonal antibody that blocks the activity of the epithelial cytokine thymic stromal lymphopoietin. In the PATHWAY phase 2b study (NCT02054130), tezepelumab significantly reduced exacerbations by up to 71% in adults with severe, uncontrolled asthma, irrespective of baseline disease phenotype. This article reports the design and objectives of the pivotal phase 3 NAVIGATOR study. Methods NAVIGATOR (NCT03347279) is an ongoing randomized, double-blind, placebo-controlled trial in adults (18–80 years old) and adolescents (12–17 years old) with severe, uncontrolled asthma, who are receiving treatment with medium- or high-dose inhaled corticosteroids plus at least one additional controller medication with or without oral corticosteroids (N = 1061). The study population includes approximately equal proportions of patients with high (≥ 300 cells/μL) and low (< 300 cells/μL) blood eosinophil counts. The study comprises a 5–6-week screening period, a 52-week treatment period and a 12-week post-treatment follow-up period. All patients will receive their prescribed controller medications without change throughout the study. The primary efficacy endpoint is the annualized asthma exacerbation rate during the 52-week treatment period. Key secondary endpoints include the effect of tezepelumab on lung function, asthma control and health-related quality of life. Discussion NAVIGATOR is evaluating the effect of tezepelumab in patients with a broad range of severe asthma phenotypes at baseline, including those with low blood eosinophil counts. The target sample size for NAVIGATOR (N = 1060) was achieved, and it is the largest clinical study of tezepelumab in severe, uncontrolled asthma to date. NAVIGATOR aims to further investigate the effect of tezepelumab on exacerbations and build on observations from the phase 2b PATHWAY study, and to demonstrate further the potential of tezepelumab to provide patients with severe, uncontrolled asthma with improvements in lung function, asthma control and health-related quality of life. Trial registration NCT03347279 (ClinicalTrials.gov). Registered 20 November 2017.

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“…Tezepelumab is a human monoclonal antibody (IgG2λ) that binds specifically to thymic stromal lymphopoietin (TSLP), blocking it from interacting with its heterodimeric receptor ( Fig. 1) [13][14][15]. TSLP is an epithelial-derived cytokine implicated in the initiation and persistence of airway inflammation in response to airborne triggers of asthma such as viruses, allergens, pollutants and other airborne irritants that interact with the airway epithelium; it is a key regulator of downstream inflammatory pathways in the airway, both T2 mediated and non-T2 mediated, as well as of other related processes such as epithelial barrier function [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

“…In the phase 2b PATHWAY study, tezepelumab reduced asthma exacerbations by up to 71% compared with placebo in patients with severe, uncontrolled asthma, and improved lung function, asthma control and patient HRQoL [14]. Exacerbation reduction was irrespective of baseline allergic or eosinophilic status, or levels of T2 inflammatory biomarkers [14,15]. Based on the reduction in exacerbations in a broad population of patients with severe asthma in PATHWAY, including those with low blood eosinophil counts, tezepelumab was granted Breakthrough Therapy Designation by the US Food and Drug Administration in 2019 for patients with severe asthma without an eosinophilic phenotype who are receiving ICS/LABA and additional asthma controllers with or without OCS [20].…”

Section: Introductionmentioning

confidence: 99%

CASCADE: a phase 2, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the effect of tezepelumab on airway inflammation in patients with uncontrolled asthma

et al. 2020

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Background Patients with severe, uncontrolled asthma, particularly those with a non-eosinophilic phenotype, have a great unmet need for new treatments that act on a broad range of inflammatory pathways in the airway. Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin, an epithelial cytokine. In the PATHWAY phase 2b study (NCT02054130), tezepelumab reduced exacerbations by up to 71% in adults with severe, uncontrolled asthma, irrespective of baseline eosinophilic inflammatory status. This article reports the design and objectives of the phase 2 CASCADE study. Methods CASCADE is an ongoing exploratory, phase 2, randomized, double-blind, placebo-controlled, parallel-group study aiming to assess the anti-inflammatory effects of tezepelumab 210 mg administered subcutaneously every 4 weeks for 28 weeks in adults aged 18–75 years with uncontrolled, moderate-to-severe asthma. The primary endpoint is the change from baseline to week 28 in airway submucosal inflammatory cells (eosinophils, neutrophils, T cells and mast cells) from bronchoscopic biopsies. Epithelial molecular phenotyping, comprising the three-gene-mean technique, will be used to assess participants’ type 2 (T2) status to enable evaluation of the anti-inflammatory effect of tezepelumab across the continuum of T2 activation. Other exploratory analyses include assessments of the impact of tezepelumab on airway remodelling, including reticular basement membrane thickening and airway epithelial integrity. At the onset of the COVID-19 pandemic, the protocol was amended to address the possibility that site visits would be limited. The amendment allowed for: at-home dosing of study drug by a healthcare professional, extension of the treatment period by up to 6 months so patients are able to attend an onsite visit to undergo the end-of-treatment bronchoscopy, and replacement of final follow-up visits with a virtual or telephone visit. Discussion CASCADE aims to determine the mechanisms by which tezepelumab improves clinical asthma outcomes by evaluating the effect of tezepelumab on airway inflammatory cells and remodelling in patients with moderate-to-severe, uncontrolled asthma. An important aspect of this study is the evaluation of the anti-inflammatory effect of tezepelumab across patients with differing levels of eosinophilic and T2 inflammation. Trial registration NCT03688074 (ClinicalTrials.gov). Registered 28 September 2018.

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Tezepelumab Treatment Effect on Annualized Rate of Exacerbations by Baseline Biomarkers in Uncontrolled Severe Asthma Patients: Phase 2b PATHWAY Study

Cited by 17 publications

References 0 publications

Tezepelumab improves patient-reported outcomes in patients with severe, uncontrolled asthma in PATHWAY

Tezepelumab improves patient-reported outcomes in patients with severe, uncontrolled asthma in PATHWAY

NAVIGATOR: a phase 3 multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma

CASCADE: a phase 2, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the effect of tezepelumab on airway inflammation in patients with uncontrolled asthma

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