Efficacy and Safety of Tezepelumab in Adults With Severe, Uncontrolled Asthma in Asia: Results From the Phase 3 DIRECTION Study.

Abstract

Tezepelumab, a human monoclonal antibody that blocks thymic stromal lymphopoietin, reduced the annualized asthma exacerbation rate (AAER) and improved lung function, asthma control, and health-related quality of life (HRQoL) in patients with severe, uncontrolled asthma (SUA) in the global, phase 3 NAVIGATOR study (NCT03347279). DIRECTION was a phase 3, multicenter, double-blind study that assessed the efficacy and safety of tezepelumab in adults with SUA in China, the Philippines, and the Republic of Korea. Patients (18-80 years old) with SUA (no baseline biomarker restrictions) were randomized 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. The primary end point was the AAER over 52 weeks. Key secondary end points were changes from baseline to week 52 in prebronchodilator forced expiratory volume in 1 second (FEV₁) and Asthma Control Questionnaire-6 (ACQ-6), Asthma Quality of Life Questionnaire (standardized) for patients 12 years and older (AQLQ[S]+12), and Asthma Symptom Diary (ASD) scores. Safety was also assessed. Overall, 400 patients received tezepelumab (n = 201) or placebo (n = 199). Tezepelumab significantly reduced AAERs versus placebo by 74% (95% confidence interval [CI]: 61, 83; P < .001) in the overall population and by 60% (95% CI: 31, 77) in patients with baseline blood eosinophil count <300 cells/μL. Tezepelumab significantly improved prebronchodilator FEV₁ (least-squares mean difference: 0.24 L [95% CI: 0.16, 0.32]) and ACQ-6, AQLQ(S)+12, and ASD scores at week 52 versus placebo (all P ≤ .001). No new safety concerns were identified. Tezepelumab reduced exacerbations and improved lung function, asthma control, and HRQoL in Asian patients with SUA, consistent with prior study findings.