Tezepelumab Reduces Severe Asthma Exacerbations by 70% in Phase 4 PASSAGE

Real-world phase 4 PASSAGE data presented at the 2026 American Thoracic Society (ATS) International Conference in Orlando, Florida, found that tezepelumab (Tezspire) reduced severe asthma exacerbations by 70%. The treatment also improved disease control across a diverse population of patients with severe uncontrolled asthma, including groups routinely excluded from or underrepresented in pivotal trials.

In an interview with HCPLive at ATS 2026, Njira Lucia Lugogo, MD, clinical professor of medicine in the Division of Pulmonary and Critical Care Medicine at the University of Michigan, discussed the implications of the data for real-world prescribing and the need for more inclusive trial design going forward.

PASSAGE Study Design: Real-World Severe Asthma Cohort

PASSAGE was a phase 4, multicenter, single-arm, open-label study enrolling patients aged ≥ 12 years with severe asthma and ≥ 2 exacerbations in the prior year. The 286-patient cohort was intentionally designed to reflect populations underrepresented in randomized controlled trials: 42% had blood eosinophil counts (BEC) ≥ 300 cells/µL, 58% had a positive allergy status, 22% were Black or African American, 7% were adolescents, 20% had comorbid COPD, and 29% were current or former smokers.

Tezepelumab Reduced Annualized Asthma Exacerbation Rate by 70% Overall

The annualized asthma exacerbation rate (AAER) decreased by 70% (95% CI: 63 to 75) from baseline to the treatment period overall. Across asthma phenotypes and underrepresented subgroups, reductions ranged from 54% to 77%, indicating consistent benefit regardless of eosinophil status, smoking history, or comorbid COPD.

"When we scaled up from the very homogeneous clinical trial population to a real-world population, we are replicating the effects and maybe even seeing more profound exacerbation reduction, which is very reassuring," Lugogo told HCPLive. "It should give us the confidence that we can use these drugs in clinical practice successfully."

Tezepelumab Improved FEV1, with Greater Gains in Patients with Impaired Lung Function

At week 52, the least-squares mean change in pre-bronchodilator FEV1 from baseline was 0.12 L (95% CI: 0.07 to 0.17) overall (n = 222). Among patients with baseline FEV1 ≤ 80% predicted — those with the most compromised lung function at enrollment — the improvement was greater, at 0.21 L (95% CI, 0.15 to 0.28; n = 138).

Clinically Meaningful Improvements in Asthma Control and Quality of Life

Clinically meaningful improvements from baseline, defined by minimum clinically important difference thresholds, were observed at week 52 across three validated instruments. Among the overall population (all n = 219), 74% achieved meaningful improvement on the Asthma Control Questionnaire-6 (ACQ-6), 63% on the Asthma Impairment and Risk Questionnaire (AIRQ), and 80% on the St. George's Respiratory Questionnaire (SGRQ). Across asthma phenotypes and underrepresented populations, response rates ranged from 64 to 86% for ACQ-6, 51 to 75% for AIRQ, and 63 to 91% for SGRQ.

Tezepelumab Efficacy in Black/African American Patients with Severe Asthma

Black and African American patients comprised 22% of the PASSAGE cohort, which is a proportion greater than what is typically seen in phase 3 severe asthma trials. Lugogo noted that this population responded well to tezepelumab without new safety signals and framed the findings in the context of a broader access gap.

"Many biologic-eligible patients are simply not receiving any biologic, so I'm hoping that this new data…is going to give us more confidence, and we'll be able to increasingly use biologics in wider patient populations,” Lugogo said.

Tezepelumab Safety Profile Consistent With Prior Trial Data

In total, 28 patients (9.8%) experienced a serious adverse event during the treatment period following tezepelumab initiation. Adverse events were consistent with the established safety profile of the drug.

PASSAGE Highlights Gaps in Severe Asthma Trial Design

Beyond the clinical findings, Lugogo called for a broader reconsideration of how severe asthma trials are structured. Patients with comorbid asthma-COPD overlap remain ineligible for most interventional trials, leaving clinicians without prospective evidence until post-authorization studies like PASSAGE are completed.

"We need to think about whether we need a paradigm shift in how we design our trials to include some of these comorbid populations so that we can have data a bit earlier and not have to wait for data generation afterwards,” Lugogo said.

Watch part 1 of our interview with Lugogo here: Tezepelumab Reduced Severe Asthma Across Phenotypes in Phase 4 PASSAGE.

Editor’s note: Relevant disclosures for Lugogo include GlaxoSmithKline, GENZYME CORPORATION, SANOFI-AVENTIS U.S., AstraZeneca Pharmaceuticals, Regeneron Pharmaceuticals, Incyte Corporation, and more.

Reference

Lugogo NL, Akuthota P, Sumino K, et al. (Poster Board # P1428) Tezepelumab in diverse real-world patients with severe asthma across different phenotypes and underrepresented populations: final results from the US phase 4 PASSAGE study. Late-breaking research was presented at the American Thoracic Society 2026 International Conference on May 18 in Orlando, Florida.