Tezepelumab Drastically Reduces OCS Use for Asthma in Open-Label Trial

Almost all patients with oral corticosteroid (OCS)-dependent severe, uncontrolled asthma achieved a maintenance OCS dose of 5 mg per day or less and more than half completely discontinued OCS while maintaining asthma control after 52 weeks of open-label tezepelumab treatment.1

Tezepelumab was originally approved by the United States (US) Food and Drug Administration (FDA) in 2021 as the first biologic therapy for treating asthma and was later approved for self-administration in 2023.2 These new data are from the multicenter, single-arm, phase 3 WAYFINDER trial (NCT05274815) and were published in The Lancet Respiratory Medicine.1

“Improvements in asthma therapies in recent years, including the advent of personalised, potentially disease-modifying biologic therapies, have resulted in the evolution of treatment goals from short-term control of symptoms and exacerbations to long-term disease remission. Although there is not yet a consensus on how to define asthma remission, the widely agreed components are the absence of systemic corticosteroid use and asthma exacerbations together with very mild or no asthma symptoms,” study investigator David J. Jackson, MBBS, MSc, PhD, Professor, Guy's Severe Asthma Centre, School of Immunology & Microbial Sciences, Guy's Hospital, King's College London, and colleagues wrote.1 “Therefore, tezepelumab shows promise in helping enable patients with severe asthma to achieve clinical remission.”

WAYFINDER was conducted between May 17, 2022, and Sept 9, 2024 and enrolled adults with severe, uncontrolled asthma receiving a maintenance OCS dose of 5–40 mg per day (or equivalent) of prednisone or prednisolone from 68 clinical centers across 11 countries (Argentina, Belgium, Bulgaria, France, Germany, Latvia, Mexico, Poland, Spain, UK, and US). In the trial, 298 participants (69.1% female; n = 206) received tezepelumab 210 mg subcutaneously once every 4 weeks for up to 52 weeks. The co-primary endpoints were the proportion of participants who reduced their prescribed maintenance OCS dose to 5 mg per day (contingent on participants demonstrating preserved adrenal function) or less without loss of asthma control and the proportion of participants who discontinued OCS without loss of asthma control and were assessed at weeks 28 and 52.1

Participants in WAYFINDER had a mean baseline maintenance OCS dose of 10.8 mg per day (SD, 6.5). Jackson and colleagues found that the proportion of participants who had a maintenance OCS dose of 5 mg per day or less without loss of asthma control was 88.9% (n = 265; 95% CI, 84.8–92.3) at week 28 and 89.9% (n = 268; 95% CI, 85.9–93.1) at week 52.1

Furthermore, 32.2% of participants (n = 96; 95% CI, 26.9–37.8) were able to discontinue OCS without loss of asthma control by week 28, increasing to 50.3% (n = 150; 95% CI, 44.5–56.2) by week 52. OCS reduction and discontinuation outcomes were consistent across prespecified subgroups defined by baseline blood eosinophil count, fractional exhaled nitric oxide, and allergy status. Serious adverse events occurred in 9.4% of participants (n = 28), most commonly asthma (13 cases) and pneumonia (3 cases), and 1.3% (n = 4) experienced adverse events that led to tezepelumab discontinuation. Two deaths occurred during the study, though neither was considered related to tezepelumab treatment.1

In a related editorial, Paola Rogliani, MD, and Luigino Calzetta, PhD, both from University of Rome “Tor Vergata” in Italy, compared the positive findings of WAYFINDER to the previously negative findings of the similar SOURCE trial of tezepelumab.3.4 The SOURCE and WAYFINDER trials of tezepelumab differed notably in design, patient populations, and outcomes. SOURCE was a rigorous, randomized, double-blind, placebo-controlled study that failed to meet its primary endpoint overall, showing meaningful OCS reduction only in patients with baseline eosinophils ≥150/μL. In contrast, WAYFINDER was a larger, open-label, non-randomized trial that enrolled OCS-dependent patients across a wider eosinophil range with striking reductions in OCS use, though its lack of a control group and higher-risk baseline profile limit direct comparison. Differences in baseline eosinophil counts and starting OCS doses further complicate interpretation, and adjusted analyses suggest that WAYFINDER’s apparent benefits may be partially explained by placebo effects seen in SOURCE.3

“In conclusion, although WAYFINDER4 provides suggestive evidence that tezepelumab might reduce OCS dependence in severe asthma, methodological limitations, baseline imbalances, and the influence of the placebo effect indicate that these findings are not definitive; well-designed randomized, placebo-controlled trials or high-quality pooled analyses are needed to confirm the OCS-sparing effect of tezepelumab,” Rogliani and Calzetta wrote.3

References

1. Jackson DJ, Lugogo NL, Gurnell M, et al. Oral corticosteroid reduction and discontinuation in adults with corticosteroid-dependent, severe, uncontrolled asthma treated with tezepelumab (WAYFINDER): a multicentre, single-arm, phase 3b trial. Lancet Resp Med. Published online November 26, 2025. doi: 10.1016/S2213-2600(25)00359-5

2. Iapoce C. FDA Approves Tezepelumab Self-Administration for Severe Asthma. Article. HCPLive. February 2, 2023. https://www.hcplive.com/view/fda-approves-tezepelumab-self-administration-severe-asthma

3. Rogliani P, Luigino Calzetta. Efficacy of tezepelumab in reducing oral corticosteroid use in severe asthma. Lancet Resp Med. Published online November 1, 2025. doi: 10.1016/s2213-2600(25)00395-9

4. Wechsler ME, Menzies-Gow A, Brightling CE, et al. Evaluation of the oral corticosteroid-sparing effect of tezepelumab in adults with oral corticosteroid-dependent asthma (SOURCE): a randomised, placebo-controlled, phase 3 study. Lancet Resp Med. Published online March 2022. doi: 10.1016/s2213-2600(21)00537-3