B32-05 Tezepelumab Improves Severe Asthma Symptoms in the First Days of Treatment Compared With Placebo in NAVIGATOR

Rationale Tezepelumab, a human monoclonal antibody, blocks thymic stromal lymphopoietin (TSLP), an epithelial cytokine involved in asthma pathogenesis. In the phase 3 NAVIGATOR study (NCT03347279) of patients with severe, uncontrolled asthma, tezepelumab reduced exacerbations and improved lung function and patient-reported outcomes, including Asthma Symptom Diary (ASD) total score, compared with placebo over 52 weeks (weekly mean ASD total score difference: −0.12 [95% CI: −0.19, −0.04]; p = 0.002). This post hoc analysis assessed improvements in ASD score with tezepelumab compared with placebo in the first days of treatment. Methods NAVIGATOR was a multicenter, randomized, double-blind, placebo-controlled study. Patients (12-80 years old) received tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. In this analysis, the least-squares (LS) mean change from baseline in ASD total score was assessed daily over the first 28 days of treatment. The mean daily ASD total score was derived from the Global Asthma Symptom item assessment each morning and evening (10 items in total). ASD scores range from 0 (no symptoms) to 4 (worst possible symptoms). Nominal p values were calculated for differences between treatment groups. Results Overall, 528 patients received tezepelumab and 531 received placebo. The weekly mean (standard deviation) ASD total score at baseline was 1.4 (0.7) for tezepelumab and 1.4 (0.7) for placebo. Tezepelumab improved ASD total score from baseline compared with placebo from day 1 (LS mean difference: −0.07 [95% CI: −0.13, 0.00]; p = 0.04). Continued improvements in ASD total score were observed through day 7 (LS mean difference −0.12 [95% CI: −0.19, −0.06]; p < 0.001) with effects sustained until day 28 (LS mean difference: −0.12 [95% CI: −0.19, −0.06]; p < 0.001) (Figure). Conclusions In patients with severe, uncontrolled asthma, treatment with tezepelumab resulted in rapid and sustained improvements in patient-reported symptoms compared with placebo, with differences observed from the first day of treatment and robust improvements seen by day 7. This abstract is funded by: AstraZeneca & Amgen