Effectiveness and Safety of Tezepelumab in a Diverse Population of US Patients with Severe Asthma: Initial Results of the PASSAGE Study

Introduction: Clinical trials for severe uncontrolled asthma (SUA) often underrepresent or exclude key patient populations. The phase 4 PASSAGE study assesses the effectiveness and safety of tezepelumab in a diverse, real-world US population of patients with SUA. Methods: PASSAGE is an ongoing, multicenter, single-arm, open-label study of patients (≥ 12 years) with SUA. The study enrolled participants across asthma phenotypes, based on blood eosinophil counts (BECs) (≥/< 300 cells/µL) and perennial aeroallergen sensitization, and underrepresented subgroups (Black/African Americans, adolescents, participants with comorbid mild to moderate chronic obstructive pulmonary disease (COPD) and smokers [≥ 10 pack-years]). Participants receive tezepelumab 210 mg subcutaneously every 4 weeks for 52 weeks. This interim analysis assessed annualized asthma exacerbation rates (AAERs) in the 12-month baseline period (before starting tezepelumab) and the treatment period, and changes from baseline to week 24 in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV₁), Asthma Control Questionnaire-6 (ACQ-6) score and health-related quality of life (HRQoL) outcomes. Results: Of 208 participants in this analysis, 41% had BEC ≥ 300 cells/µL, 56% had confirmed allergy, 17% were Black/African American, 5% were adolescents, 13% had comorbid COPD, and 23% were smokers. The AAER decreased by 76% (95% CI (confidence interval): 69, 81) from baseline to the treatment period; comparable reductions were observed across asthma phenotypes and underrepresented subgroups. The least squares mean change from baseline to week 24 in pre-BD FEV₁ was 0.11 L (95% CI: 0.06, 0.17) overall and 0.19 L (95% CI: 0.12, 0.25) among participants with baseline pre-BD FEV₁ ≤ 80% predicted. Clinically meaningful improvements from baseline to week 24 were observed for ACQ-6 score and HRQoL outcomes. No new safety signals were identified. Conclusion: The PASSAGE study of US patients with SUA treated with tezepelumab demonstrates substantial reductions in AAERs across asthma phenotypes and underrepresented subgroups, with clinically meaningful improvements in lung function, asthma control and HRQoL. Trial Registration: ClinicalTrials.gov identifier, NCT05329194.