Efficacy of Tezepelumab in Patients With Evidence of Severe Allergic Asthma: Results From the Phase 3 NAVIGATOR Study

Allergic asthma is the most common asthma phenotype in both adults and children. Thymic stromal lymphopoietin is an epithelial cytokine released in response to allergens and nonallergy mediated airway irritation, driving airway inflammation and eosinophilia. Tezepelumab is a human monoclonal antibody that binds Thymic stromal lymphopoietin and could be an effective biologic treatment in patients with severe allergic asthma.

The study enrolled 1059 patients aged 12 to 80 years old diagnosed with asthma who were receiving a medium-high dose inhaled corticosteroid plus at least one additional controller medication for at least 3 months. Of patients, 680 (64.2%) had perennial aeroallergen sensitivity and 361 (34.1%) did not.

Patients were randomized to treatment with either 210 mg tezepelumab or placebo subcutaneously every 4 weeks for 52 weeks. The primary endpoint was annualized asthma exacerbation rate (AAER) after 52 weeks. Secondary endpoints included change in patient recorded outcomes (PROs) as documented on symptom questionnaires, as well as change in eosinophil count, fractional exhaled nitric oxide levels and total serum IgE level from baseline to week 52. A negative binomial regression model was used to estimate the difference in AAERs between the two study groups.

Tezepelumab treatment reduced the AAER compared with placebo by 58% in patients with perennial aeroallergen sensitivity and by 51% in patients without perennial aeroallergen sensitivity. In the tezepelumab group, patients also had increased forced expiratory volume 1, reduction in symptoms based on PROs, and reduction in eosinophil counts and serum IgE levels.

Tezepelumab reduces asthma exacerbations in patients with allergic asthma and nonallergic asthma. Tezepelumab can improve lung function and PROs, while also decreasing T2 biomarker levels.

Tezepelumb can treat patients with nonallergic asthma and those with allergic asthma with varying degrees of T2 inflammation. This adds another treatment option for patients with asthma. More studies are needed to translate this study’s success to younger pediatric populations.