JP Llanos Ackert, MD, C Ambrose, MD: New Data Support Tezepelumab for Asthma

Article

Investigators Dr. Jean-Pierre Llanos Ackert and Dr. Chris Ambrose share insight on the efficacy of tezepelumab in severe, uncontrolled asthma, and baseline predictors of enhanced response which support tezepelumab as a promising biologic treatment option.

Jean-Pierre Llanos Ackert, MD

Jean-Pierre Llanos Ackert, MD

Data from 2 exploratory post hoc analyses on the NAVIGATOR phase 3 trial were presented at the American Thoracic Society (ATS) 2023 International Conference in Washington DC. The study aimed to assess the efficacy of tezepelumab in patients with severe, uncontrolled asthma.

Chris Ambrose, MD

Chris Ambrose, MD

Study investigators Jean-Pierre Llanos Ackert, MD, executive medical director, Global Medical Affairs, Amgen, and Chris Ambrose, MD, franchise head, US Medical, Respiratory, AstraZeneca provided an overview of the key findings in an email interview with HCPLive.

Llanos Ackert and Ambrose Stated:

Key Findings

We presented 2 exploratory post hoc analyses from the NAVIGATOR Phase 3 trial, which support the efficacy of tezepelumab in patients with severe, uncontrolled asthma.
  • NAVIGATOR efficacy among those with and without prior omalizumab use: The first abstract analyzed tezepelumab efficacy by prior omalizumab use. Data showed that tezepelumab consistently reduced asthma exacerbations in patients with severe, uncontrolled asthma irrespective of prior omalizumab use.
  • NAVIGATOR baseline predictors of an enhanced response to tezepelumab: The second abstract analyzed baseline predictors of an enhanced response to tezepelumab treatment versus placebo. As responses to biologics vary in patients with severe, uncontrolled asthma based on differences in patients’ baseline characteristics, this post hoc analysis assessed predictors of an enhanced response to tezepelumab treatment using a machine learning model.
  • The results showed that the strongest baseline predictors of an enhanced reduction in exacerbations with tezepelumab versus placebo were the number of prior year exacerbations, lung function, and FeNO levels.
  • Baseline clinical characteristics that predicted enhanced response in lung function and asthma control were also identified. No baseline factor was associated with non-response.
These exploratory analyses add to the growing body of evidence for tezepelumab (brand name TEZSPIRE), which is the first and only biologic approved for severe asthma with no phenotype (e.g., eosinophilic or allergic) or biomarker limitation within its approved label.

The Role of TSLP in Asthma Control

Thymic stromal lymphopoietin (TSLP) is a key epithelial cytokine that has multiple effects within the asthma inflammatory cascade.
TSLP plays a central role in the initiation and persistence of allergic, eosinophilic, and other types of airway inflammation and pathophysiology associated with severe asthma, including airway hyperresponsiveness.
Studies in patients with asthma have shown that TSLP is associated with asthma severity, reduced lung function, reduced steroid response, exaggerated T2 responses to viral infections, and potential airway remodeling.
Tezepelumab binds to and blocks TSLP from interacting with its receptor, reducing multiple aspects of airway inflammation (e.g. reducing blood and airway eosinophils, FeNO and IgE) as well as airway hyperresponsiveness. However, the mechanism of action of TEZSPIRE in severe asthma has not been definitively established.

Baseline Predictors of Enhanced Response to Tezepelumab

Pre-bronchodilator forced expiratory volume in 1 second (FEV1) and Asthma Control Questionnaire-6 (ACQ-6) score.

For FEV1 improvement with tezepelumab versus placebo, the top 3 predictors of enhanced response to tezepelumab treatment were baseline blood eosinophil count, FEV1 reversibility, and percent predicted baseline FEV1.
For ACQ6 score improvement with tezepelumab versus placebo, the top 3 predictors of enhanced response to tezepelumab treatment were baseline ACQ6 score, blood eosinophil count, and body mass index.
As noted above, for the primary endpoint of asthma exacerbation improvement with tezepelumab versus placebo, the top 3 predictors of an enhanced response were the number of prior year exacerbations, baseline lung function, and FeNO levels.
These different factors highlight the complexity of predicting patient responses to biologics as well as the varying beneficial effects of blocking TSLP on multiple distinct outcomes. Overall, these exploratory findings may help to identify patients who will have an enhanced treatment response to tezepelumab.
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