Half of Adults with Severe Asthma Treated with Tezepelumab Discontinue OCS Use at 52 Weeks: Phase 3b WAYFINDER Trial

New data from the phase 3b WAYFINDER study show tezepelumab, a human monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), significantly reduced oral corticosteroid (OCS) dependence in adults with severe asthma. Nearly 90% of participants successfully lowered their maintenance OCS dose to 5 mg/day or less, and half completely eliminated OCS use by week 52 while maintaining asthma control. The primary study results were presented at the 2025 American Thoracic Society annual meeting in San Francisco, May 16-21.

David J Jackson, MBBS, PhD

Courtesy Kings College London

This single-arm, open-label trial evaluated tezepelumab's OCS-sparing effect in 298 adults with severe asthma who required daily prednisone or prednisolone (5-40 mg/day or equivalent) for at least 3 months prior to enrollment. Inclusion required at least 1 asthma exacerbation in the 12 months before study screening.

At week 28, 88.9% of participants achieved an OCS dose of 5 mg/day or less, increasing slightly to 89.9% by week 52. Complete OCS discontinuation was achieved by 32.2% of participants at week 28, rising to 50.3% by week 52, according to the study abstract.

A post hoc analysis revealed that 82.2% of participants maintained their OCS dose at 5 mg/day or less without loss of asthma control at week 52 when systemic corticosteroid treatment was related to adrenal insufficiency.

These results represent a significant improvement over the earlier phase 3 SOURCE trial (NCT03406078), which did not meet its primary endpoint, though it did show OCS dose reduction in tezepelumab recipients with baseline blood eosinophil counts 150 cells/μL or more compared to placebo. WAYFINDER enrolled a larger cohort with a more diverse disease profile, the authors wrote.

Mean age of WAYFINDER participants was 54 years; 69% were women and the majority self-identified as White. At baseline participants were receiving high-dose inhaled corticosteroids and a long-acting beta agonist for at least 6 months in addition to the required corticosteroid dose (mean 10.8 mg/day). Average number of disease exacerbations within the past year was 1.8, authors reported.

All participants received tezepelumab 210 mg subcutaneously every 4 weeks. After 4 weeks of stable OCS dosing, a 48-week steroid reduction period followed, during which steroid does was reduced by 1 to 5 mg every 1 to 4 weeks. Reductions were based on OCS starting dose in each period and larger and more frequent reductions followed higher starting doses.

Co-primary endpoints, assessed at weeks 28 and 52, were proportion of participants who reduced their daily prescribed OCS dose to 5 mg daily or less without loss of asthma control and the proportion of participants who discontinued OCS without loss of asthma control. OCS dose reductions less than 5 mg/day were contingent on participants retaining adrenal function, assessed via an initial morning cortisol test and then either adrenocorticotropic hormone stimulation tests or repeated morning serum cortisol tests.

Of the 298 patients who initiated treatment, 273 completed the 52-week study.

The safety profile observed in the WAYFINDER study remained consistent with previous tezepelumab trials, though specific safety data were not detailed in the abstract.

These findings suggest tezepelumab may offer a valuable therapeutic option for adults with OCS-dependent severe asthma, potentially reducing the well-documented adverse effects associated with long-term systemic corticosteroid use, including bone, cardiovascular, metabolic, gastrointestinal and psychiatric disorders as well as adrenal insufficiency.

Tezepelumab was approved for the add-on maintenance treatment of adult and pediatric patients aged 12 years and older with severe asthma.