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Clinical Trial
. 2025 Jul;42(7):3334-3353.
doi: 10.1007/s12325-025-03231-6. Epub 2025 May 19.

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

Njira L Lugogo  1 , Praveen Akuthota  2 , Kaharu Sumino  3 , Sameer K Mathur  4 , Autumn F Burnette  5 , Andrew W Lindsley  6 , Jean-Pierre Llanos  7 , Claudio Marchese  8 , Christopher S Ambrose  9 , Benjamin Emmanuel  10
Affiliations
Clinical Trial

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

Njira L Lugogo et al. Adv Ther. 2025 Jul.

Erratum in

Abstract

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.

Keywords: Asthma; Biologic; Phenotype; Real-world; Severe asthma; Tezepelumab; Thymic stromal lymphopoietin; Underrepresented populations.

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Conflict of interest statement

Declarations. Conflict of Interest: Njira L. Lugogo has received consultancy fees for participation in advisory boards from Amgen, AstraZeneca, Genentech, GSK, Novartis, Regeneron Pharmaceuticals, Sanofi and Teva Pharmaceuticals; has received honoraria for nonspeaker bureau presentations from AstraZeneca and GSK; has received speaker fees (own content) from NIOX; has received travel support from AstraZeneca; and has received research support to her institution from Amgen, AstraZeneca, Avillion, Genentech, Gossamer Bio, GSK, Regeneron Pharmaceuticals, Sanofi and Teva Pharmaceuticals. Praveen Akuthota has received consultancy fees and research support from Amgen, AstraZeneca, Connect Biopharma, GSK, Regeneron and Sanofi; has received research support from the American Partnership for Eosinophilic Disorders, the National Institutes of Health and Regeneron Pharmaceuticals; has received royalties from UpToDate; and has received fees for continuing medical education presentations from Advancing Knowledge in Healthcare, Medscape, MJH Life Sciences, PeerView, PRIME Continuing Medical Education, Projects in Knowledge, Rockpointe and Vindico Medical Education. Kaharu Sumino has received consultancy fees for participation in an advisory board from AstraZeneca. Sameer K. Mathur has received consultancy fees from AstraZeneca, GSK and Regeneron Pharmaceuticals, and has received fees for presentations from AstraZeneca and GSK. Autumn F. Burnette has received consultancy fees for participation in advisory boards and panel presentations from Amgen, AstraZeneca, GSK, Regeneron Pharmaceuticals and Sanofi, and has received speaker bureau fees from Amgen, AstraZeneca, Regeneron Pharmaceuticals and Sanofi. Andrew W. Lindsley and Jean-Pierre Llanos are employees of Amgen and own stock in Amgen. Claudio Marchese, Christopher S. Ambrose and Benjamin Emmanuel are employees of AstraZeneca and may own stock or stock options in AstraZeneca. Ethical Approval: The study is being conducted in accordance with the ethical principles of the Declaration of Helsinki, International Council for Harmonisation Good Clinical Practice guidelines and applicable regulatory requirements. Approvals from the Advarra Central Institutional Review Board (MD, USA and ON, Canada) and local independent ethics committees were obtained for all study sites (see supplementary material for a full list of ethics committees and Institutional Review Boards that covered the study sites). All participants provided written informed consent at the start of the study.

Figures

Fig. 1
Fig. 1
PASSAGE study design. Q4W every 4 weeks, SC subcutaneously
Fig. 2
Fig. 2
Relative reductions in the AAER during the 12-month periods before (baseline period) and after (treatment period) tezepelumab initiation. AAER annualized asthma exacerbation rate, CI confidence interval
Fig. 3
Fig. 3
Relative reductions in AAERs in the overall population, asthma phenotype (by BEC and allergy status) and underrepresented subgroups, and patient-reported asthma trigger types. Patient-reported asthma triggers were assessed using the asthma trigger survey, which is a one-question survey conducted to collect data on the activities and/or other factors that trigger asthma symptoms and/or exacerbations at baseline. Participants can have more than one reported asthma trigger. AAER annualized asthma exacerbation rate, BEC blood eosinophil count, CI confidence interval, COPD chronic obstructive pulmonary disease, CRSsNP chronic rhinosinusitis without nasal polyps, CRSwNP chronic rhinosinusitis with nasal polyps
Fig. 4
Fig. 4
Changes from baseline to week 24 in pre-BD FEV1 across subgroups in the overall population and in participants who had a baseline percent predicted pre-BD FEV1 of ≤ 80%. Mean (SD) baseline values for pre-BD FEV1 in the overall population and in participants who had percent predicted pre-BD FEV1 of ≤ 80% were 2.2 L (0.8) and 1.9 L (0.6), respectively. Mean (SD) baseline values for all subgroups are provided in Table S1 in the electronic supplementary material. BECs are provided in cells/µL. BD bronchodilator, BEC blood eosinophil count, CI confidence interval, COPD chronic obstructive pulmonary disease, FEV1 forced expiratory volume in 1 second, LS least squares, SD standard deviation
Fig. 5
Fig. 5
Change in a ACQ-6 score, b AIRQ sum score and c SGRQ total score from baseline to week 24 in the overall population. Responder definitions were based on the MCID thresholds for the outcomes, which were absolute change from baseline (decrease) of ≥ 0.5 (ACQ-6 score), ≥ 2 (AIRQ sum score) and ≥ 4 (SGRQ total score). Responder rates are based on the n used for LS mean comparisons, which excludes participants with missing data. Baseline is the last nonmissing assessment on or before the first dose of tezepelumab at week 0. ACQ-6 Asthma Control Questionnaire-6, AIRQ Asthma Impairment and Risk Questionnaire, CI confidence interval, LS least squares, MCID minimal clinically important difference, SD standard deviation, SGRQ St. George’s Respiratory Questionnaire
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