WAYFINDER updates boost tezepelumab role in OCS-dependent severe asthma

Updated results from the open-label, phase IIIb WAYFINDER study continue to support the oral corticosteroid (OCS)-sparing efficacy of tezepelumab in the treatment of patients with OCS-dependent severe asthma.

“After 52 weeks of tezepelumab treatment, 90 percent of patients had a maintenance OCS dose of ≤5 mg/day without loss of asthma control,” said Dr David Jackson from Guy’s and St Thomas’ National Health Service Foundation Trust, London, UK, at ATS 2025. Loss of asthma control was defined as an increase in Asthma Control Questionnaire-6 (ACQ-6) score of ≥0.5 from the previous assessment or experiencing an asthma exacerbation.

This finding was consistent with that observed at week 28 (88.9 percent). Of note, the mean baseline maintenance OCS dose was 10.8 mg/day. [ATS 2025, session C14]

This endpoint was achieved across patient subgroups at week 52, with the most profound effect observed in subgroups who had a daily OCS dose of ≤10 mg at baseline (94.3 percent) and those whose allergy status at baseline was positive in any FEIA* (92.6 percent).

What is more, half of the tezepelumab recipients discontinued OCS without loss of asthma control. This was a marked increase from week 28, which only saw a third of recipients achieving this endpoint. This outcome was also achieved across subgroups, with the most discontinuations seen in the subgroups of patients with blood eosinophil count (BEC) ≥300 cells/µL (57.6 percent) and those with a daily OCS dose ≤10 mg at baseline (54.6 percent).

Other improvements

Two-thirds of participants remained exacerbation-free despite OCS dose reductions over 52 weeks of treatment. The annualized asthma exacerbation rate at week 52 was down to 0.57 from the baseline rate of 1.8.

Despite OCS dose reduction, there was a modest improvement in post-bronchodilator FEV₁ over the course of the study. The adjusted mean change from baseline was 0.07 L.

Other week-52 improvements were the adjusted mean changes from baseline ACQ-6, AQLQ(S)+12** overall, and SGRQ*** total scores (-1.15, 1.18, and -16.8, respectively). The corresponding mean scores at baseline were 2.64, 3.97, and 55.8.

The minimal clinically important differences (MCIDs) were 0.5 points for ACQ-6 and AQLQ(S)+12 and 4 points for SGRQ. Hence, the MCID improvements were more than twofold higher for ACQ-6 and AQLQ(S)+12 and fourfold higher for SGRQ after tezepelumab treatment, Jackson explained.

OCS discontinuation a priority in asthma management

OCS reduction and discontinuation are important goals of asthma management, as prolonged OCS use leads to adverse effects, including bone, cardiovascular, metabolic, gastrointestinal, and psychiatric disorders, and adrenal insufficiency. [Eur Respir J 2018;52:1800703; J Clin Endocrinol Metab 2015;100:2171-2180; Eur J Intern Med 2013;24:714-720; Semin Arthritis Rheum 2016;46:133-141]

“Steroids cause a lot of harm to our patients. Trying to get patients off maintenance prednisolone is a real priority for severe asthma,” Jackson said.

In the phase III OCS-sparing SOURCE study, there was an improvement in OCS sparing with tezepelumab among participants with baseline BECs of ≥150 cells/µL. However, the primary endpoint was not met. [Lancet Respir Med 2022;10:650-660]

WAYFINDER evaluated the OCS-sparing ability of tezepelumab in a cohort of OCS-dependent severe asthma patients much larger than the SOURCE study population.

In WAYFINDER, the team evaluated adults with severe asthma who were on high-dose inhaled corticosteroids and long‑acting beta 2-agonists for ≥6 months and daily OCS (prednisone/prednisolone 5–40 mg/day or equivalent) for ≥3 months and those with ≥1 exacerbation in the 12 months prior to screening.

A total of 298 participants (mean age 54.4 years, 69.1 percent women) were given SC tezepelumab 210 mg Q4W for up to 52 weeks. Following a 4-week induction phase on a stable OCS dose, a 48-week OCS reduction and maintenance phase ensued. Over three-quarters of participants were on OCS ≤10 mg/day at baseline.

“In severe asthma patients who are prednisolone-dependent, a year of tezepelumab allowed 90 percent of patients to wean their prednisolone to ≤5 mg/day, half to come off prednisolone completely, two-thirds to remain exacerbation-free even though their prednisolone had been removed, and we saw this across biomarker categories,” Jackson concluded.