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Tezepelumab – good success rates in various types of severe asthma

Presented by
Prof. Michael E. Wechsler, National Jewish Health, Denver, CO, USA
ATS 2021
Tezepelumab showed convincing results for the treatment of severe asthma. Besides significantly reducing exacerbation rates in many different inflammatory profiles, the first-in-class TSLP blocker also improved asthma control and quality of life.

Tezepelumab is a monoclonal antibody with specific inhibition of thymic stromal lymphopoietin (TSLP) resulting in hindering TSLP to cooperate with its receptor thus acting upstream of various cytokines involved not only in type 2 inflammation, but also in neutrophil activation and mast cell effects [1,2]. So, why is this so interesting for the treatment of asthma? “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 and 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, CO, USA) described the current situation [3].

The results of the phase 3 NAVIGATOR (NCT03347279) study were one of breaking news of the ATS 2021 congress [3]. 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 and ≥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 and 0.93 in the placebo and the tezepelumab arm, respectively (P<0.001). “Exciting about the NAVIGATOR study was that tezepelumab reduced exacerbation in the overall population and 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 were significantly reduced by 79%. Lung function improved overall, with greatest differences to placebo in those with eosinophils ≥300 cells/µL. The efficacy of tezepelumab also resulted in significant amelioration in asthma control (P<0.001), asthma symptom diary score (P=0.002), and asthma quality of life (P<0.001). “Importantly, tezepelumab also reduced blood eosinophil counts, exhaled nitric oxide, and IgE levels over the 52 weeks of this treatment study,” emphasised Prof. Wechsler.

Overall, adverse events were more frequent in placebo patients than in the tezepelumab receivers (80.8% vs 77.1%) [4]. Most common in both groups were nasopharyngitis, upper respiratory tract infection, and headache. Serious adverse events also occurred more often in the placebo group compared with the tezepelumab arm (13.7% vs 9.8%). Discontinuation of treatment was induced by adverse events in 3.6% (placebo) and 2.1% (tezepelumab).

  1. Gauvreau GM, et al. N Engl J Med. 2014;370(22):2102-10.
  2. Corren J, et al. N Engl J Med. 2017;377(10):936-46.
  3. 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.
  4. Menzies-Gow A, et al. N Engl J Med. 2021;384(19):1800-09.

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