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

Abstract

Background: Tezepelumab, a human monoclonal antibody that blocks thymic stromal lymphopoietin, reduced 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).

Objective: 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 Republic of Korea.

Methods: Patients (18-80 years) 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 endpoint was AAER over 52 weeks. Key secondary endpoints were changes from baseline to week 52 in pre-bronchodilator FEV₁ and Asthma Control Questionnaire-6 (ACQ-6), Asthma Quality of Life Questionnaire (standardized) for patients aged ≥12 years (AQLQ[S]+12), and Asthma Symptom Diary (ASD) scores. Safety was also assessed.

Results: Overall, 400 patients received tezepelumab (n=201) or placebo (n=199). Tezepelumab significantly reduced AAERs versus placebo by 74% (95% 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 pre-bronchodilator 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.

Conclusions: Tezepelumab reduced exacerbations and improved lung function, asthma control, and HRQoL in Asian patients with SUA, consistent with prior study findings.

Gov identifier: NCT03927157.

Keywords: Annualized asthma exacerbation rate; Asian population; Biologic; Severe uncontrolled asthma; Tezepelumab; Thymic stromal lymphopoietin.