Monoclonal antibody tezepelumab cuts severe asthma in phase IV clinical trial

A report of phase 4 PASSAGE data presented at the 2026 American Thoracic Society International Conference in May 2026 has shown that tezepelumab reduced asthma exacerbations across severe asthma phenotypes and in patient groups often underrepresented in clinical trials

A phase 4 clinical trial has found that tezepelumab significantly reduced asthma exacerbations in real-world patients with severe asthma, including groups often excluded from or underrepresented in conventional clinical trials.

The findings from PASSAGE were presented at the 2026 American Thoracic Society International Conference and have provided further evidence for the safety and effectiveness of tezepelumab across a broader severe asthma population. The study is called “Tezepelumab in Real-World U.S. Patients with Severe Asthma Across Phenotypes and Underrepresented Populations: The Phase 4 PASSAGE Study”.

Tezepelumab is a monoclonal antibody therapy that was approved in 2021 for the treatment of severe asthma. The drug targets thymic stromal lymphopoietin, an epithelial cytokine involved early in the inflammatory cascade that can contribute to airway inflammation and asthma exacerbations. By acting upstream of several inflammatory pathways, tezepelumab has been developed as a treatment option for patients with severe asthma across different disease phenotypes.

PASSAGE was designed as a multicentre phase 4 clinical trial to assess the drug in a broader and more representative patient population than is typically enrolled in pivotal clinical trials. Researchers recruited 286 adults and adolescents with severe asthma and followed them for 12 months of treatment.

The study found that tezepelumab was associated with 70 per cent fewer asthma exacerbations. The reduction was observed across all patient subgroups assessed in the trial, including:

• • smokers
  • patients with overlapping asthma and chronic obstructive pulmonary disease (COPD)
  • adolescents
  • Black or African American patients.

These groups are often absent from, or poorly represented in, traditional asthma trials, which can limit the relevance of trial data to routine clinical care.

“The premise of PASSAGE was to focus on underrepresented populations, and to gather more evidence so that we can be more confident in using tezepelumab in these patients,” said Dr Njira Lugogo, first author and clinical professor of medicine in the division of pulmonary and critical care medicine at the University of Michigan, Ann Arbor, Michigan, USA.

“The study results were really reassuring in terms of both safety and efficacy,” she said.

Beyond the reduction in exacerbations, patients treated with tezepelumab showed improved lung function, better asthma control and higher quality of life scores. The study also reported less reliance on systemic corticosteroids which are often used to manage severe asthma symptoms but can cause important adverse effects when used repeatedly or for prolonged periods.

The treatment was reported to be safe, with no novel or unexpected side effects identified during the study. Qualitative interviews also suggested that patients were satisfied with the therapy, an important consideration for long-term treatment in chronic respiratory disease.

Lugogo said the drug reduced exacerbations across asthma phenotypes but appeared particularly effective in patients with Type 2 asthma. Type 2 asthma is a common and often severe subtype associated with systemic inflammation and immune pathways that can drive persistent airway disease.

She also said the results were important for patients whose lung function may be affected by other respiratory conditions or exposures.

“It worked well in smokers and people with comorbid COPD,” said Dr Lugogo.

“That was very important to me, because I see these patients in clinical practice, and I wanted to feel confident that treating them with tezepelumab would be successful,” she added.

The findings are likely to be of particular interest to clinicians who treat patients with both asthma and COPD. These patients often have more severe illness, a higher symptom burden and more complications than those with asthma alone. However, they tend to be excluded from both asthma and COPD trials which leaves a gap in evidence for treatment decisions.

“In clinical trials, they’re always excluded – they’re excluded from asthma studies, and they’re excluded from COPD studies,” said Dr Lugogo.

Although controlled clinical trials remain central to evidence-based medicine, the PASSAGE study has highlighted the value of real-world evidence to assess medicines in the types of patients seen in everyday clinical practice. For severe asthma, where disease biology, comorbidities and treatment response can vary widely, such data can help clinicians to make more confident treatment decisions for patients who do not fit neatly into conventional trial criteria.

“Real-world evidence is extremely important,” Lugogo said.

For further reading please visit: 10.1093/ajrccm/aamag225