BACKGROUND: In some patients with moderate-to-severe asthma, particularly those 
with noneosinophilic inflammation, the disease remains uncontrolled. This trial 
evaluated the efficacy and safety of tezepelumab (AMG 157/MEDI9929), a human 
monoclonal antibody specific for the epithelial-cell-derived cytokine thymic 
stromal lymphopoietin (TSLP), in patients whose asthma remained uncontrolled 
despite treatment with long-acting beta-agonists and medium-to-high doses of 
inhaled glucocorticoids.
METHODS: In this phase 2, randomized, double-blind, placebo-controlled trial, we 
compared subcutaneous tezepelumab at three dose levels with placebo over a 
52-week treatment period. The primary end point was the annualized rate of 
asthma exacerbations (events per patient-year) at week 52.
RESULTS: The use of tezepelumab at a dose of 70 mg every 4 weeks (low dose; 145 
patients), 210 mg every 4 weeks (medium dose; 145 patients), or 280 mg every 2 
weeks (high dose; 146 patients) resulted in annualized asthma exacerbation rates 
at week 52 of 0.26, 0.19, and 0.22, respectively, as compared with 0.67 in the 
placebo group (148 patients). Thus, exacerbation rates in the respective 
tezepelumab groups were lower by 61%, 71%, and 66% than the rate in the placebo 
group (P<0.001 for all comparisons). Similar results were observed in patients 
regardless of blood eosinophil counts at enrollment. The prebronchodilator 
forced expiratory volume in 1 second at week 52 was higher in all tezepelumab 
groups than in the placebo group (difference, 0.12 liters with the low dose 
[P=0.01], 0.11 liters with the medium dose [P=0.02], and 0.15 liters with the 
high dose [P=0.002]). A total of 2 patients in the medium-dose group, 3 in the 
high-dose group, and 1 in the placebo group discontinued the trial regimen 
because of adverse events.
CONCLUSIONS: Among patients treated with long-acting beta-agonists and 
medium-to-high doses of inhaled glucocorticoids, those who received tezepelumab 
had lower rates of clinically significant asthma exacerbations than those who 
received placebo, independent of baseline blood eosinophil counts. (Funded by 
MedImmune [a member of the AstraZeneca Group] and Amgen; PATHWAY 
ClinicalTrials.gov number, NCT02054130 .).