Tezepelumab Achieves Dual Benefit in Severe Asthma, Improving Control with Reduced Steroid Dependence

Nearly 90% of adults with severe, steroid-dependent asthma reduced their oral corticosteroid dose to 5 mg or less daily while maintaining asthma control after treatment with tezepelumab (Tezpire, AstraZeneca), according to results from the WAYFINDER trial presented at the American College of Chest Physicians (CHEST) 2025 Annual Meeting in Chicago. The proportion of patients achieving well-controlled asthma increased 9-fold over 52 weeks, from just 3.0% at baseline to 26.9% by study end, investigators reported.1,2

The findings represent a significant advance for patients with severe asthma who remain dependent on oral corticosteroids despite maximal therapy. Prolonged steroid use carries substantial risks, including bone loss, metabolic dysfunction, and immunosuppression, making steroid-sparing strategies a critical unmet need in severe asthma management.

Tezepelumab, a human monoclonal antibody, works by blocking thymic stromal lymphopoietin (TSLP), an epithelial cytokine that sits at the top of the inflammatory cascade in asthma. By targeting this upstream mediator, the drug addresses multiple inflammatory pathways simultaneously, offering a mechanism distinct from other available biologics that target specific downstream mediators like IgE or interleukins.

Tezepelumab is indicated as add-on maintenance therapy for control of severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) in people aged 12 years and older whose asthma is not controlled with their current treatment

The WAYFINDER TRIAL

Presented at CHEST by David Jackson, MBBS FRCP MSc PhD, professor and clinical director Guy's Severe Asthma Centre at Guy's Hospital King's College Londone, WAYFINDER (NCT05274815) was an open-label, single-arm, multicenter phase 3b trial, enrolled 298 adults with severe asthma requiring maintenance oral corticosteroids (prednisone or prednisolone 5–40 mg/day) for at least 3 months prior to enrollment. All participants received subcutaneous tezepelumab 210 mg every 4 weeks for up to 52 weeks.

A 4-week induction phase with stable steroid dosing preceded a 48-week reduction and maintenance phase. Steroid tapering proceeded cautiously, with reductions of less than 5 mg per day contingent on preserved adrenal function, assessed through morning cortisol testing and adrenocorticotropic hormone stimulation tests.

Steroid-Sparing Efficacy. At baseline, Jackson reported, participants were receiving a mean maintenance oral corticosteroid dose of approximately 10.8 mg daily. By week 28, 88.9% of participants had reduced their dose to 5 mg or less per day, a proportion that remained stable at 89.9% through week 52. Notably, 82.2% of those who achieved the lower maintenance dose did not experience loss of asthma control at week 52, when adjusting for systemic corticosteroid use related to adrenal insufficiency.

Asthma Control Improvements. Tezepelumab drove meaningful improvements in disease control. Jackson highlighted that at baseline, 80.2% of participants had uncontrolled asthma, a proportion that fell to 34.9% by week 52. The mean Asthma Control Questionnaire-6 score improved from 2.6 at baseline to 1.5 at week 28 and 1.4 at week 52, representing clinically meaningful reductions in symptom burden. By trial conclusion, 47.3% of participants had achieved at least partially controlled asthma.

Of the 298 participants who initiated treatment, 273 completed the full study period. The safety profile observed was consistent with previous trials of tezepelumab.

Tezepelumab Clinical Trials

Tezepelumab received FDA approval in 2021 for severe asthma in patients aged 12 and older. Earlier trial results were mixed: the SOURCE study failed to meet its primary endpoint of significant OCS reduction without loss of asthma control, though subgroup analysis showed efficacy in patients with baseline eosinophil counts ≥150 cells/μL. The subsequent DESTINATION extension trial, following patients for 104 weeks total, demonstrated that 66.7% of tezepelumab-treated patients discontinued OCS compared with 46.9% receiving placebo, providing the foundation for the more robust WAYFINDER investigation.

As the biologic landscape in severe asthma continues to expand, tezepelumab's unique mechanism targeting TSLP positions it as a valuable option for difficult-to-treat patients, particularly those with persistent inflammation despite maximal conventional therapy. The WAYFINDER findings support its role in personalized respiratory care strategies aimed at both disease modification and harm reduction.

REFERENCES

Jackson DJ, Lugogo N, Gurnell M, et al. Tezepelumab reduces and eliminates OCS use in OCS-dependent patients with severe asthma: primary results from the phase 3b WAYFINDER study. Am J Respir Crit Care Med. 2025;211:A5231. doi:10.1164/ajrccm.2025.211.Abstracts.A5231

1. Tezepelumab significantly improves severe asthma control. News release. American Medical Journal. October 30, 2025. Accessed November 4, 2025. https://www.emjreviews.com/en-us/amj/respiratory/news/tezepelumab-significantly-improves-severe-asthma-control/

Study to evaluate efficacy and safety of tezepelumab in reducing oral corticosteroid use in adult patients with severe asthma (WAYFINDER). ClinicalTrials.gov identifier: NCT05274815. Updated October 23, 2024. Accessed November 4, 2025. https://clinicaltrials.gov/study/NCT05274815

Tezspire (tezepelumab-ekko). Prescribing information; Astra Zeneca; 2025. Accessed November 4, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761224s000lbl.pdf