Efficacy of Tezepelumab in Severe, Uncontrolled Asthma: Pooled Analysis of the PATHWAY and NAVIGATOR Clinical Trials

Corren, Jonathan; Menzies‐Gow, Andrew; Chupp, Geoffrey; Israel, Elliot; Korn, Stephanie; Cook, Bill; Ambrose, Christopher S.; Hellqvist, Åsa; Roseti, Stephanie L; Molfino, Néstor A.; Llanos, Jean-Pierre; Martin, Neil; Bowen, Karin; Griffiths, José-Marie; Parnes, Jane R.; Colice, Gene

doi:10.1164/rccm.202210-2005oc

Cited by 42 publications

(60 citation statements)

References 21 publications

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“…These findings are further supported by a pooled analysis of data from PATHWAY and NAVIGATOR, in which an AAER reduction over 52 weeks of 62% (95% CI: 53, 70) with tezepelumab 210 mg Q4W compared with placebo was reported in patients with perennial aeroallergen sensitization (Figure 4). 46 Furthermore, in this pooled analysis, tezepelumab reduced the rate of exacerbations that required hospitalization or an emergency department visit over 52 weeks by 80% (95% CI: 61, 90) in this patient subgroup.…”

Section: Efficacy Of Tezepelumab On Exacerbations In Allergic Asthmamentioning

confidence: 71%

“…In a post hoc analysis of NAVIGATOR data, tezepelumab reduced the AAER compared with placebo by 77% (95% CI: 65, 85), 77% (95% CI: 54, 89) and 74% (95% CI: 29, 90) in patients with a blood eosinophil count of at least 500, at least 750 and at least 1000 cells/μL, respectively 63 . Additionally, in a pooled analysis of data from the PATHWAY and NAVIGATOR studies, tezepelumab reduced the rate of exacerbations that required hospitalization or an emergency department visit by 90% (95% CI: 76, 96) in patients with a baseline blood eosinophil count of at least 300 cells/μL 46 …”

Section: Efficacy Of Tezepelumab On Exacerbations In Eosinophilic Asthmamentioning

confidence: 99%

“…In patients with perennial aeroallergen sensitization, pooled secondary outcome data from the PATHWAY and NAVIGATOR studies demonstrated improvements from baseline to Week 52 with tezepelumab 210 mg Q4W compared with placebo in lung function (FEV 1 : 0.22 L vs. 0.13 L; difference, 0.09 L [95% CI: 0.03, 0.14]; minimum clinically important difference [MCID], 0.1 L 54 ). 46 Improvements were also reported with tezepelumab compared with placebo in patient‐reported outcome measures: Asthma Control Questionnaire‐6 score (−1.48 vs. −1.23; difference, −0.25 [95% CI: −0.39, −0.10]; MCID, 0.5 55 ) and Asthma Quality of Life Questionnaire (standardized) for patients 12 years or older overall score (1.49 vs. 1.21; difference, 0.28 [95% CI: 0.12, 0.44]; MCID, 0.5 56 ). 46 …”

Section: Efficacy Of Tezepelumab On Lung Function and Patient‐reporte...mentioning

confidence: 99%

“… 46 Improvements were also reported with tezepelumab compared with placebo in patient‐reported outcome measures: Asthma Control Questionnaire‐6 score (−1.48 vs. −1.23; difference, −0.25 [95% CI: −0.39, −0.10]; MCID, 0.5 55 ) and Asthma Quality of Life Questionnaire (standardized) for patients 12 years or older overall score (1.49 vs. 1.21; difference, 0.28 [95% CI: 0.12, 0.44]; MCID, 0.5 56 ). 46 …”

Section: Efficacy Of Tezepelumab On Lung Function and Patient‐reporte...mentioning

confidence: 99%

“…In clinical studies, tezepelumab has been shown to reduce exacerbations in patients with elevated blood eosinophil counts, with pooled data from the PATHWAY and NAVIGATOR studies indicating a 71% (95% CI: 62, 78) reduction in the AAER over 52 weeks with tezepelumab 210 mg Q4W compared with placebo in patients with a baseline blood eosinophil count of at least 300 cells/μL (Figure 5). 46 A reduction compared with placebo was also observed in patients with a baseline blood eosinophil count of at least 150 cells/μL (63% [95% CI: 54, 70]) 46 . In a post hoc analysis of NAVIGATOR data, tezepelumab reduced the AAER compared with placebo by 77% (95% CI: 65, 85), 77% (95% CI: 54, 89) and 74% (95% CI: 29, 90) in patients with a blood eosinophil count of at least 500, at least 750 and at least 1000 cells/μL, respectively 63 .…”

Section: Efficacy Of Tezepelumab On Exacerbations In Eosinophilic Asthmamentioning

confidence: 99%

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Tezepelumab in patients with allergic and eosinophilic asthma

Caminati,

Buhl,

Corren

et al. 2023

Allergy

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Asthma is a heterogeneous disease commonly driven by allergic and/or eosinophilic inflammation, both of which may be present in severe disease. Most approved biologics for severe asthma are indicated for specific phenotypes and target individual downstream type 2 components of the inflammatory cascade. Tezepelumab, a human monoclonal antibody (immunoglobulin G2λ), binds specifically to thymic stromal lymphopoietin (TSLP), an epithelial cytokine that initiates and sustains allergic and eosinophilic inflammation in asthma. By blocking TSLP, tezepelumab has demonstrated efficacy across known asthma phenotypes and acts upstream of all current clinically used biomarkers. In a pooled analysis of the phase 2b PATHWAY (NCT02054130) and phase 3 NAVIGATOR (NCT03347279) studies, compared with placebo, tezepelumab reduced the annualized asthma exacerbation rate over 52 weeks by 62% (95% confidence interval [CI]: 53, 70) in patients with perennial aeroallergen sensitization (allergic asthma); by 71% (95% CI: 62, 78) in patients with a baseline blood eosinophil count ≥300 cells/μL; and by 71% (95% CI: 59, 79) in patients with allergic asthma and a baseline blood eosinophil count ≥300 cells/μL. This review examines the efficacy and mode of action of tezepelumab in patients with allergic asthma, eosinophilic asthma and coexisting allergic and eosinophilic phenotypes.

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Section: Efficacy Of Tezepelumab On Exacerbations In Allergic Asthmamentioning

confidence: 71%

Section: Efficacy Of Tezepelumab On Exacerbations In Eosinophilic Asthmamentioning

confidence: 99%

Section: Efficacy Of Tezepelumab On Lung Function and Patient‐reporte...mentioning

confidence: 99%

Section: Efficacy Of Tezepelumab On Lung Function and Patient‐reporte...mentioning

confidence: 99%

Section: Efficacy Of Tezepelumab On Exacerbations In Eosinophilic Asthmamentioning

confidence: 99%

See 3 more Smart Citations

Tezepelumab in patients with allergic and eosinophilic asthma

Caminati,

Buhl,

Corren

et al. 2023

Allergy

Self Cite

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Phase 1 Safety and Pharmacokinetics Study of TAVO101, an Anti‐Human Thymic Stromal Lymphopoietin Antibody for the Treatment of Allergic Inflammatory Conditions

Han,

Fung,

Zhang

et al. 2024

The Journal of Clinical Pharma

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TAVO101 is a humanized anti‐human thymic stromal lymphopoietin (TSLP) monoclonal antibody under clinical development for the treatment of atopic dermatitis (AD) and other allergic inflammatory conditions. The crystallizable fragment region of the antibody was engineered for half‐life extension and attenuated effector functions. This Phase 1, double‐blinded, randomized, placebo‐controlled study assessed the safety, tolerability, pharmacokinetics, and immunogenicity of TAVO101 in healthy adult subjects in seven ascending dose cohorts. Subjects received a single intravenous administration of TAVO101 or placebo with a 195‐day follow‐up. TAVO101 was safe and well tolerated. The incidences and severities of treatment‐emergent adverse events were mostly mild and comparable between the active and placebo groups, with no trends of dose relationship. There were no severe adverse events, deaths, or treatment‐related withdrawals. TAVO101 exhibited a linear pharmacokinetic profile, low clearance, and a median elimination half‐life of 67 days in healthy subjects. All TAVO101‐treated subjects tested negative for anti‐drug antibodies. To support development in AD, TAVO101 was studied in an oxazolone‐induced AD model in hTSLP transgenic mice and demonstrated efficacy. This long‐acting anti‐TSLP antibody has the potential for stronger and sustained allergic inflammatory disease control. The results from this study warranted further clinical development of TAVO101 in patients.

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The new biologic drugs: Which children with asthma should get what?

Hillson,

Saglani,

Bush

2024

Pediatric Pulmonology

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Novel biologics (targeted antibody therapies) have revolutionized the management of severe childhood asthma. However, it is important that the right biologic is selected for the right patient, and understanding the evidence base for each biologic is crucial. Currently, four biologics (all monoclonal antibodies) are licensed in the UK for the treatment of children with severe asthma ‐ omalizumab (Xolair), mepolizumab (Nucala), and dupilumab (Dupixent) in children aged 6 years and over; and tezepelumab (Tezspire), only in children aged 12 years and over. Tezepelumab is the only licensed biological that may be beneficial in severe asthma without evidence of Type 2 inflammation. All have a good safety profile but varying degrees of clinical efficacy in children, with wide variation in treatment responsiveness between individual patients. When selecting biologics for severe asthma, it is essential to remember the limitations of the current pediatric evidence. At present, there are no results from randomized, head‐to‐head trials of biologics in severe asthma. TREAT is an ongoing trial comparing omalizumab to mepolizumab and will be one of the first to provide such evidence. We must be especially aware of the dangers of extrapolating data from adults to children, because the pathophysiology and role of biomarkers may differ significantly from adult asthma. Given the current level of knowledge, even after treatment has been initiated, children should be regularly reviewed to determine the efficacy of treatment, side‐effect profile and consideration of when treatment with the biologic should be discontinued.

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Efficacy of Tezepelumab in Severe, Uncontrolled Asthma: Pooled Analysis of the PATHWAY and NAVIGATOR Clinical Trials

Cited by 42 publications

References 21 publications

Tezepelumab in patients with allergic and eosinophilic asthma

Tezepelumab in patients with allergic and eosinophilic asthma

Phase 1 Safety and Pharmacokinetics Study of TAVO101, an Anti‐Human Thymic Stromal Lymphopoietin Antibody for the Treatment of Allergic Inflammatory Conditions

The new biologic drugs: Which children with asthma should get what?

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