The reductions were seen as early as week 2 and was sustained throughout the 52 week study.
New research shows Tezepelumab results in a meaningful reduction of inflammatory cytokines and biomarkers for patients with severe asthma.
A team, led by Janet Griffiths, PhD, Translational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, evaluated the effect of Tezepelumab on the levels of airway and circulating inflammatory cytokines and biomarkers to provide meachanistic insight into the clinical effects of the drug on patients with severe asthma.
He data was presented during the American Academy of Allergy, Asthma & Immunology Annual Meeting (AAAAI) 2022.
Tezepelumab is a human monoclonal antibody that blocks the actions of thymic stromal lymphopoietin and reduces downstream airway inflammation.
Tezepelumab was approved late last year by the Food and Drug Administration as an injection and add-on maintenance treatment to improve severe asthma symptoms when used with a patient’s current asthma medicine. It is the first treatment for severe asthma without biomarker or phenotype limitations.
In the phase 3, randomized, placebo-controlled NAVIGATOR study, the investigators examined adult and adolescent patients with severe, uncontrolled asthma. The patients were equally randomized to receive either Tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks.
The NAVIGATOR study included a total of 1059 patients between the ages of 12 and 80.
The investigators assessed fractional exhaled nitric oxide (FeNO, ppb), blood eosinophil counts (cells/μL), total immunoglobulin (Ig)E (IU/mL), and serum interleukin (IL)-5 and IL-13 levels (ng/L) at baseline and multiple points throughout the study.
They used a repeated measures model to estimate mean percentage changes from baseline per treatment group and differences between treatment groups. They also log-transformed the data prior to analysis.
The drug resulted in a 30.6% (95% CI, 25.6-35.2) in FeNO at week 52, as well as a 41.4% reduction in blood eosinophil count (95% CI, 37.0-45.4), 30.1% reduction in IgE (95% CI 24.7-35.1), 55.9% drop in IL-5 (95% CI 50.5-60.6) and 45.7% decrease in IL-13 (95% CI, 40.2-50.7). Reductions compared to placebo were observed by week 4 for IgE and by week 2 for all other cytokines and biomarkers. These reductions were sustained through to week 52.
“Tezepelumab treatment reduced airway and circulating inflammatory cytokines and biomarkers from as early as week 2 onwards,” the authors wrote. “These reductions validate previous results and support the role of tezepelumab in reducing TSLP-mediated asthma inflammation.”
Also, as part of the NAVIGATOR study, investigators examined the annualized asthma exacerbation rate (AAER) as well as a number of patients without exacerbations on a seasonal basis.
When compared to placebo, tezepelumab reduced the AAER by 63% in winter, 46% in spring, 62% in summer and 54% in fall. Additionally, patients who took tezepelumab had fewer asthma exacerbations in winter (81.7% vs 66.6%), spring (84.3% vs 76.3%), summer (86.8% vs 73.1%) and fall (79.4% vs 66.6%).
The study, “Tezepelumab Reduces Inflammatory Biomarkers as Early as Week 2 and Maintains Reductions Until Week 52 in the Phase 3 NAVIGATOR Severe Asthma Trial,” was published online in the Journal of Allergy and Clinical Immunology.