Tezepelumab Achieves Dual Benefit in Adults with Severe Asthma: Daily Dose

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On November 4, 2025, we reported on primary results from the phase 3b WAYFINDER clinical trial presented at the American College of Chest Physicians (CHEST) 2025 Annual Meeting in Chicago.

The study

The WAYFINDER study was a phase 3b, open-label, single-arm trial designed to evaluate the oral corticosteroid (OCS)-sparing effects of tezepelumab. Researchers enrolled adults with severe asthma across various baseline blood eosinophil counts who had been receiving a maintenance OCS dose of 5–40 mg/day for at least 3 months. All participants received 210 mg of tezepelumab administered subcutaneously every 4 weeks for a total of 52 weeks. The trial structure included an initial 4-week induction phase on a stable OCS dose, followed by a 48-week OCS reduction and maintenance phase.

To ensure patient safety during the reduction phase, OCS dose decreases to levels below 5 mg/day were only permitted if patients retained adequate adrenal function. This was monitored through initial morning cortisol tests followed by either repeated morning serum cortisol tests or adrenocorticotropic hormone stimulation tests. The researchers assessed 2 coprimary endpoints at weeks 28 and 52: the proportion of participants who successfully reduced their daily mOCS dose to <5 mg/day without losing asthma control, and the proportion who were able to completely discontinue OCS while maintaining control.

The findings

Over the 52-week study, the vast majority of participants (89.9%) successfully reduced their daily maintenance OCS dose to <5 mg/day without losing asthma control. This marked a steady improvement from the 88.9% who reached this threshold at week 28. The study also highlighted the drug's potential for total OCS elimination. While 32.2% of participants had discontinued OCS by week 28, this number grew to 50.3% by week 52, meaning over half of the patients were able to stop OCS entirely. Additionally, in a post hoc analysis, 82.2% of patients maintained a dose of <5 mg/day even when their ongoing steroid use was primarily due to adrenal insufficiency rather than a lack of asthma control.

Authors' comments

"Most patients in this broad severe asthma population treated with tezepelumab achieved clinically meaningful reductions in mOCS dose to ≤5 mg/day or completely discontinued OCS, while maintaining asthma control. Over 80% of patients were able to reduce their mOCS dose to ≤5 mg/day when the reason for systemic corticosteroid treatment was related to adrenal insufficiency."

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