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Tezepelumab Effective in Severe Asthma Cohorts Stratified by Age at Onset, Inflammatory Phenotype, and Allergen Sensitization


AAAAI 2023. The TSLP inhibitor was superior to placebo in 2 post hoc analyses of the PATHWAY and NAVIGATOR clinical trials.

Tezepelumab, the novel thymic stromal lymphopoietin (TSLP) inhibitor, reduced exacerbations in a population of patients with severe uncontrolled asthma grouped by age of asthma onset and by inflammatory phenotype, characteristics that may significantly impact the efficacy of biologic therapies, according to study authors.

Tezepelumab also signficantly reduced exacerbations in patients grouped by season-specific allergic reactions.

All these findings from post hoc analyses of pooled data from the phase 2b PATHWAY and phase 3 NAVIGATOR clinical trials will be presented in full at the 2023 Annual Meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI).

Tezepelumab is approved in the US for add-on maintenance treatment of adult and pediatric patients aged 12 years and older with severe asthma and has no biomarker or phenotype limitations in its labeling.

Both PATHWAY (n=550) and NAVIGATOR (n=1061) were multicenter randomized, placebo-controlled clinical trials with similar designs and evaluated the effect of tezepelumab vs placebo on the annualized asthma exacerbation rate (AAER). Participants were aged 12 to 80 years with severe uncontrolled asthma and receiving standard of care. The cohorts were randomized to receive either tezepelumab 210 mg or placebo subcutaneously every 4 weeks for up to 52 weeks.

For the current post hoc analysis1, patients were grouped by age of asthma onset (childhood onset, <18 years; adult-onset, ≥18 years) in combination with inflammatory phenotype (non-eosinophilic, baseline blood eosinophil count [BEC] <150 cells/μL; baseline BEC ≥150 cells/μL; or allergy to a perennial aeroallergen).

Over the 52-week study period, tezepelumab reduced AAER vs placebo by:

  • 53% (95% CI: 34–67) in patients with childhood-onset, allergic asthma (tezepelumab, n=181; placebo, n=180)
  • 49% (95% CI: 9–72) in patients with childhood-onset, noneosinophilic asthma (tezepelumab, n=58; placebo, n=57)
  • 67% (95% CI: 57–74) in patients with adult-onset, eosinophilic asthma (tezepelumab, n=330; placebo, n=332)
  • 54% (95% CI: 37–67) in patients with adult-onset, nonallergic asthma (tezepelumab, n=198; placebo, n=204)

In the broad population of patients with severe uncontrolled asthma represented by these 2 trial cohorts, tezepelumab reduced exacerbations versus placebo regardless of age of disease onset or inflammatory phenotype.

Seasonal allergy

Results of a second post hoc analysis2, this of the NAVIGATOR trial alone, demonstrated that tezepelumab effectively reduced AAER vs placebo during specific allergy seasons in patients with severe, uncontrolled asthma.

Seasonal allergen exposure may “contribute to spatiotemporal variations in asthma exacerbations,” write first author Jonathan Corren, MD, and coauthors in the study abstract. Tezepelumab in the phase 3 NAVIGATOR clinical trial reduced AAER in study patients across all seasons. The current analysis assessed AAER by specific season among patients who researchers grouped by baseline allergen sensitization to a panel of common aeroallergens: silver birch, Japanese cedar, ragweed, and mixed grass pollens. Sensitization was determined by fluorescence enzyme immunoassay.

Compared with placebo, tezepelumab significantly reduced AAER in patients with seasonal allergy in each season and by:

  • Winter: 54% (95% CI: 27-71)
  • Spring: 63% (95% CI: 36-78)
  • Summer: 51% (95% CI: 19-70)
  • Fall: 54% (95% CI: 31-70)

After matching climates, Corren et al report that patients with seasonal allergy experienced more exacerbations during seasons of peak pollen exposure. Additional analysis found that during these peak exposures, tezepelumab vs placebo reduced the AAER during the spring allergy season (March 1 to June 15) in patients with seasonal allergy by 59% (95% CI: 29, 77) and in those without seasonal allergy by 48% (95% CI: 17, 67).

During the fall allergy season (September) tezepelumab reduced AAER by 70% (95% CI: 33, 87) in participants with seasonal allergy and by 48% (95% CI: −11, 75) among those without seasonal allergic response.

Corren and team write in conclusion that “tezepelumab reduced exacerbations during the relevant seasons, consistent with its mechanism targeting TSLP in the airway epithelium.”

The study abstracts are also available in a February supplement to the Journal of Allergy and Clinical Immunology

1. Mathur S, Hill J, Ambrose C, et al. Effect of tezepelumab in patients wtih severe unccontrolled asthma by age of onset, allergic status, and eosinophilic endotype. J Clin Allergy Immunol. J Allergy Clin Immunol. 2023;151. doi:10.1016/j.jaci.2022.12.057

2. Corren J, Lindsley A, Spahn J, et al. Tezepelumab reduces exacerbations across all seasons in patients with severe uncontrolled asthma with seasonal allergy: results from the phase 3 NAVIGATOR study. J Allergy Clin Immunol. 2023;151. doi:10.1016/j.jaci.2022.12.606

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