Real-World Study Confirms Tezepelumab Efficacy in Underrepresented Severe Asthma Populations
Key Insights
The phase 4 PASSAGE study demonstrated that tezepelumab reduced asthma exacerbations by 70% across diverse patient populations typically excluded from clinical trials.
Significant improvements were observed in Black patients, adolescents, smokers, and patients with asthma-COPD (search) overlap, addressing critical gaps in severe asthma (search) treatment evidence.
The study enrolled 286 patients and showed clinically meaningful improvements in lung function, asthma control, and quality of life alongside a 50% reduction in systemic corticosteroid use.
A new real-world study has demonstrated that tezepelumab, a monoclonal antibody therapy for severe asthma (search), maintains its clinical efficacy across diverse patient populations that are typically underrepresented in clinical trials. The phase 4 PASSAGE study, presented at the 2026 ATS International Conference and published in the American Journal of Respiratory and Critical Care Medicine, provides crucial evidence for the drug's effectiveness in Black patients, adolescents, smokers, and patients with asthma-COPD (search) overlap.
Study Design and Patient Population
The multicenter, single-arm open-label PASSAGE study enrolled 286 adults and adolescents aged 12 years and older with severe asthma (search) who experienced two or more exacerbations in the prior year. The diverse cohort included 22% Black patients (n=63), 7% adolescents aged 12-17 years (n=19), 20% with comorbid mild to moderate COPD (search) (n=57), and 29% smokers with 10 or more pack-years (n=83).
Patients received subcutaneous 210 mg doses of tezepelumab every 4 weeks through 52 weeks, with the last dose administered at week 48. Researchers stratified patients based on blood eosinophil counts of 300 cells/μL and higher (42%) or lower, and by the presence of perennial aeroallergen sensitization (58%).
Dramatic Reduction in Asthma Exacerbations
The study revealed a 70% reduction in the overall annualized asthma exacerbation rate (AAER), falling from 2.88 to 0.87 (95% CI, 63%-75%). This benefit was observed consistently across all patient subgroups, with particularly notable results in specific populations:
- Black patients: 73% reduction (3.29 to 0.9; 95% CI, 59%-82%)
- Adolescents: 71% reduction (2.32 to 0.67; 95% CI, 41%-86%)
- Patients with COPD: 65% reduction (2.7 to 0.94; 95% CI, 46%-78%)
- Smokers: 64% reduction (2.88 to 1.04; 95% CI, 50%-74%)
The most substantial improvements were seen in patients with elevated blood eosinophil counts (≥300 cells/μL), where reductions reached 75-77% regardless of allergy status.
Comprehensive Clinical Improvements
Beyond exacerbation reduction, patients experienced clinically meaningful improvements across multiple outcome measures. Pre-bronchodilator FEV1 increased by 0.12 L overall (95% CI, 0.07-0.17), with even greater improvements of 0.21 L (95% CI, 0.15-0.28) in patients whose baseline FEV1 was 80% or less of predicted values.
Quality of life measures showed robust improvements across patient groups:
- 74% reported clinically meaningful improvements in Asthma Control Questionnaire-6 scores
- 63% showed improvements in Asthma Impairment and Risk Questionnaire scores
- 80% demonstrated improvements in St. George's Respiratory Questionnaire scores
The study also documented a greater than 50% reduction in systemic corticosteroid exposure, addressing a critical concern in severe asthma (search) management.
Addressing Clinical Practice Gaps
"Clinical trials in severe uncontrolled asthma often underrepresent or exclude many of the patients that clinicians see in everyday practice," explained Dr. Njira Lugogo, first author and clinical professor of medicine in the Division of Pulmonary and Critical Care Medicine at the University of Michigan. "That creates an important gap in our understanding of how biologic therapies perform across the broader severe asthma (search) community."
Dr. Lugogo highlighted the particular significance of results in patients with asthma-COPD (search) overlap, noting that "these patients are excluded from all asthma and COPD trials, yet suffer the most exacerbations and oral steroid exposure." The 65% reduction in exacerbations observed in this population provides new confidence for clinicians treating these complex patients.
Safety Profile Maintained
The study confirmed tezepelumab's established safety profile, with no new or unexpected side effects identified. Twenty-eight patients (9.8%) experienced serious adverse events, a rate consistent with the drug's known safety profile from previous clinical trials. In qualitative interviews, patients reported satisfaction with the treatment.
Clinical Implications
The PASSAGE study results provide critical real-world evidence supporting tezepelumab's use across diverse patient populations. As Dr. Lugogo noted, "These findings are significant because they show that the benefits seen with tezepelumab in clinical trials translate into clinical practice."
The study's focus on underrepresented populations addresses a significant unmet need in severe asthma (search) care, where patients with comorbidities or demographic characteristics that lead to trial exclusion often lack evidence-based treatment options. The consistent efficacy across all phenotypes, with particular effectiveness in Type 2 asthma (search) patients, reinforces tezepelumab's broad therapeutic potential.
Tezepelumab, approved in 2021 for severe asthma (search) treatment, represents an important addition to the biologic therapy landscape, and these real-world findings support its use in the diverse patient populations that clinicians encounter in daily practice.