Home > Tezepelumab for severe asthma – a rising star

Tezepelumab for severe asthma – a rising star

Presented by
Prof. Michael E. Wechsler, National Jewish Health, Denver, Colorado, USA
Conference
ATS 2021
In the phase 3 NAVIGATOR trial, the first-in-class TSLP blocker tezepelumab demonstrated significant and meaningful improvements in a population with a wide range of allergic types and biomarker categories. Not only was the exacerbation rate reduced, but the quality of life improved meaningfully.

“Inflammation in asthma remains a complex heterogeneous and dynamic process and even with biologic treatment, 60% of US patients with severe asthma have suboptimal controlled disease. There is a need for alternative treatments for severe asthma that treat a wider spectrum of inflammation,” Prof. Michael E. Wechsler (National Jewish Health, Denver, Colorado, USA) described the current situation [1]. Tezepelumab is a monoclonal antibody with specific inhibition of thymic stromal lymphopoietin (TSLP), thus acting upstream of various cytokines involved not only in type 2 inflammation, but also in neutrophil activation and mast cell effects.

As one of the newest trials, Prof. Wechsler presented the results of the phase 3 NAVIGATOR study (NCT03347279). NAVIGATOR included patients with severe, poorly controlled asthma and ≥2 exacerbations in the last 12 months. Among the study participants were equal rates of patients with blood eosinophil counts <300 cells/µL or ≥300 cells/µL at screening. Over 1,000 patients were randomised to receive either 210 mg of tezepelumab or placebo every 4 weeks over 52 weeks while continuing their background controller medication. They were followed for 12 more weeks thereafter.

The study met its primary endpoint by a significant reduction of 56% in the annualised asthma exacerbation rate (AAER): 2.10 versus 0.93 in the placebo versus the tezepelumab arm, respectively (P<0.001). “What was exciting about the NAVIGATOR study, was that tezepelumab reduced exacerbations in the overall population and also in patients with a broad range of inflammatory profiles,” stated Prof. Wechsler. Among those groups were patients with high and low eosinophil counts, high and low exhaled nitric oxide levels, as well as positive and negative perennial-specific IgE status. AAER leading to hospitalisation or emergency room visits was significantly reduced by 79%. Lung function improved overall, with the greatest differences to placebo in those with eosinophils ≥300 cells/µL. The efficacy of tezepelumab also resulted in a significant amelioration in asthma control, asthma symptom diary score, and quality of life. “Importantly, tezepelumab also reduced blood eosinophil counts, exhaled nitric oxide, and IgE levels over the 52 weeks of this treatment study,” said Prof. Wechsler.

  1. Wechsler ME. Latest clinical evidence from phase 3 tezepelumab trials in severe asthma. Session B007-Breaking news: clinical trial results in pulmonary medicine. ATS 2021 International Conference, 14-19 May.




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