B32-46 Tezepelumab in Diverse Real-World Patients With Severe Asthma Across Different Phenotypes and Underrepresented Populations: Final Results From the US Phase 4 PASSAGE Study

Rationale

Clinical trials in severe asthma often exclude or underrepresent key patient populations. The PASSAGE study (NCT05329194) evaluated the effectiveness and safety of tezepelumab in a diverse, real-world cohort of US patients with severe, uncontrolled asthma that included different asthma phenotypes and underrepresented populations.

Methods

PASSAGE was a phase 4, multicenter, single-arm, open-label study of patients (≥12 years old) with severe asthma and ≥2 exacerbations in the previous year. The study enrolled patients with prespecified asthma phenotypes defined by blood eosinophil count (BEC; ≥/<300 cells/µL) and allergy status (with/without any perennial aeroallergen sensitization) at baseline. Patients from four prespecified underrepresented populations were also enrolled: Black/African American patients, adolescents (12-17 years old), patients with comorbid mild to moderate COPD and smokers with ≥10 pack-years. Patients received tezepelumab 210 mg subcutaneously every 4 weeks for 52 weeks (last dose: week 48). The primary outcome assessed annualized asthma exacerbation rates (AAERs) in the 12-month baseline and treatment periods. Secondary outcomes included pre-bronchodilator forced expiratory volume in 1 second (FEV1) and Asthma Control Questionnaire-6 (ACQ-6), Asthma Impairment and Risk Questionnaire (AIRQ) and St George’s Respiratory Questionnaire (SGRQ) scores at baseline and week 52.

Results

Of 286 patients enrolled, 42% had BECs ≥300 cells/µL, 58% had positive allergy status, 22% were Black/African American, 7% were adolescents, 20% had comorbid COPD and 29% were smokers. Between the baseline and treatment periods, the AAER decreased by 70% (95% CI: 63-75) overall and by 54-77% across asthma phenotypes and underrepresented populations (Figure). For pre-bronchodilator FEV1, the least-squares mean change from baseline at week 52 was 0.12 L (95% CI: 0.07-0.17) overall (n = 222) and 0.21 L (95% CI: 0.15-0.28) among patients with a pre-bronchodilator FEV1 ≤80% predicted at baseline (n = 138). At week 52, clinically meaningful improvements (based on minimum clinically important difference) from baseline in ACQ-6, AIRQ and SGRQ scores were observed in 74%, 63% and 80% of patients overall (all n = 219), respectively, with robust results across asthma phenotypes and underrepresented populations (range: ACQ-6, 64-86%; AIRQ, 51-75%; SGRQ, 63-91%). Twenty-eight patients (9.8%) reported a serious adverse event during the treatment period after tezepelumab initiation. Adverse events were consistent with the known safety profile of tezepelumab.

Conclusions

The final results of the PASSAGE study of US patients with severe, uncontrolled asthma treated with tezepelumab demonstrated substantial reductions in asthma exacerbations across asthma phenotypes and underrepresented populations, with clinically meaningful improvements in lung function, asthma control and health-related quality of life.

This abstract is funded by: AstraZeneca and Amgen Inc