B22-21 Efficacy and Safety of Tezepelumab Versus Placebo in Reducing OCS Use in OCS-Dependent Patients With Severe Asthma: Results From the Phase 3 Sunrise Study

Abstract Rationale Tezepelumab blocks the activity of thymic stromal lymphopoietin (TSLP), implicated in asthma pathogenesis. The phase 3 SUNRISE study aimed to evaluate the efficacy and oral corticosteroid (OCS)-sparing effect of tezepelumab in patients with severe, OCS-dependent asthma. Methods SUNRISE (NCT05398263) was a multicenter, double-blind, placebo-controlled, parallel-group study in patients (18-80 years) with severe, OCS-dependent asthma. After OCS optimization, patients were randomized 2:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 28 weeks. The primary endpoint was the categorized percent reduction from baseline in the daily maintenance OCS dose at week 28 while maintaining asthma control. The key secondary endpoint was the change from baseline in pre-bronchodilator forced expiratory volume in one second (pre-BD FEV1) at week 28. Other secondary endpoints included exacerbation rates and changes from baseline in the Asthma Control Questionnaire-6, Asthma Quality of Life Questionnaire (standardized) for patients aged ≥ 12 years and St. George’s Respiratory Questionnaire scores, peak expiratory flow and biomarker levels (blood eosinophil count [BEC] and levels of fractional exhaled nitric oxide [FeNO] and serum total immunoglobulin E [IgE]). Safety was also evaluated. Results Overall, only 122 patients (tezepelumab n = 83, placebo n = 39) out of the planned 207 patients received treatment (75.4% women, 54.9% White, mean age: 52.2 years); 25 patients (20.5%) did not complete the study owing to study termination due to recruitment challenges. Baseline mean daily OCS doses were 14.4 mg and 12.6 mg in the tezepelumab and placebo groups, respectively. The odds of reaching a category of greater percent OCS reduction at week 28 were higher with tezepelumab than placebo (cumulative odds ratio: 2.93 [95% confidence interval: 1.43, 6.03]; p=0.003; Table). Tezepelumab treatment versus placebo resulted in improvements in pre-BD FEV1 from baseline to week 28 (mean [standard deviation], tezepelumab: 0.24 L [0.50]; placebo: −0.02 L [0.31]). There were greater numerical improvements with tezepelumab versus placebo for all secondary endpoints. No safety concerns were identified for tezepelumab. Conclusions The SUNRISE study met its primary endpoint despite the reduced sample size, with tezepelumab treatment leading to greater reductions from baseline in daily OCS dose versus placebo at week 28. There were greater numerical improvements with tezepelumab versus placebo in lung function, asthma control, health-related quality of life and BEC, FeNO and serum total IgE levels, despite the reduction achieved in the daily OCS dose. No new safety concerns were identified for tezepelumab. This abstract is funded by: AstraZeneca & Amgen