Newly reported findings from the NAVIGATOR phase III trial showed the novel biologic tezepelumab to have significant efficacy in a subpopulation of patients with uncontrolled asthma and comorbid eczema.
Treatment with the investigational human monoclonal antibody was associated with a 56% reduction in exacerbations over one year compared to placebo in patients with eczema—also known as atopic dermatitis—which was similar to the reduction seen in patients without eczema.
The latest NAVIGATOR findings were presented at the annual meeting of the European Academy of Allergy and Clinical Immunology, EAACI Hybrid Congress 2021, held July 10-12.
Earlier this month, the U.S. Food and Drug Administration accepted a Biologic License Application (BLA) and granted priority review status to tezepelumab. The biologic was granted Breakthrough Therapy Designation status by the FDA in the fall of 2018 for patients with severe asthma without an eosinophilic phenotype.
Tezepelumab is a human monoclonal antibody, administered via subcutaneous injection, that targets thymic stromal lymphopoietin (TSLP), which is an epithelial-cell-derived cytokine which has been implicated in multiple asthma pathways. In asthma patients, TSLP levels correlate with airway obstruction, disease severity and glucocorticoid resistance and they have been shown to play a role in airway structural cell and immune cell interactions not exclusively driven by T2 inflammation.
In the NAVIGATOR trial, published in mid-May in The New England Journal of Medicine, the annualized rate of asthma exacerbations among adult and adolescent study participants was found to be significantly lower in patients with severe, uncontrolled asthma treated with tezepelumab than placebo, including patients with eosinophilic asthma and those with low blood eosinophil counts (<300 cells per microliter) at baseline.
Researcher Andrew Menzies-Gow, MD, of Royal Brompton Hospital, London, and colleagues, noted that the currently approved biologics have not shown consistent efficacy in patients with eosinophil counts of less than 150 cells per microliter.
Treatment with tezepelumab was also associated with better lung function, asthma control, and health-related quality of life compared to placebo.
In the newly reported analysis, the NAVIGATOR investigators compared outcomes among tezepelumab-treated study participants with and without comorbid eczema.
In their poster presented at the EAACI Congress, Menzies-Gow and colleagues noted that because atopic dermatitis is a common comorbidity in patients with severe asthma, evaluating the efficacy of tezepelumab in patients with the condition was a pre-specified exploratory objective of NAVIGATOR.
Patients 12 years and older with asthma that was not adequately controlled with inhaled corticosteroids and at least one additional controller medication with or without oral corticosteroids were recruited for the NAVIGATOR trial; they were randomized 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks.
Of the 1,061 randomized patients, 1,059 received either the biologic (n=528) or placebo (n=531), and a total of 127 patients (12%) had comorbid atopic dermatitis at baseline (69 in the tezepelumab group and 58 in the placebo group).
Patients with comorbid eczema had higher blood eosinophil counts (median, 310 cells/μL vs 240 cell/μL) at baseline and higher serum total immunoglobulin E (IgE) levels (median, 371.0 IU/mL vs 177.2 IU/mL) at baseline, compared to those without comorbid atopic dermatitis.
Among the main findings:
- The annualized asthma exacerbation rate (AAER) over 52 weeks was similar in study participants with and without atopic dermatitis in both the placebo and active-treatment groups. Compared to placebo, tezepelumab reduced the AAER over 52 weeks by 58% (95% CI, 27-75) in patients without eczema and by 56% (95% CI, 46-64) in patients with comorbid eczema.
- The least-squares mean difference between tezepelumab and placebo in pre-bronchodilator FEV1 at week 52 was 0.12 L (95% CI, −0.02 to 0.27) in patients with eczema and 0.14 L (95% CI, 0.08-0.19) in patients without eczema. FEV1 improvements were identified as early as week 2 of treatment and were sustained of 52 weeks in both groups.
- Patient-reported improvements, assessed using validated asthma control questionnaires, were similar in tezepelumab-treated patients with and without comorbid eczema. Clinically meaningful improvements from baseline (≥4 points in the St. George’s Respiratory Questionnaire (SGRQ) total scores) were reported in tezepelumab-treated patients with and without eczema.
The researchers concluded that the findings “further support the benefits of tezepelumab in a broad population of patients with severe, uncontrolled asthma.”
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Newly reported findings from the NAVIGATOR phase III trial showed the novel biologic tezepelumab to have significant efficacy in a subpopulation of patients with uncontrolled asthma and comorbid eczema.
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Treatment with the investigational human monoclonal antibody was associated with a 56% reduction in exacerbations over one year compared to placebo in patients with eczema.
Salynn Boyles, Contributing Writer, BreakingMED™
This research was funded by AstraZeneca and Amgen.
Menzies-Gow reports grants from AstraZeneca, during the conduct of the study; personal fees from GlaxoSmithKline, personal fees from Novartis, personal fees from Roche, personal fees and other from Teva, personal fees from Sanofi, personal fees from Vectura, grants and personal fees from AstraZeneca, outside the submitted work.
Cat ID: 100
Topic ID: 80,100,730,449,100,637,192,63,925
