Tezepelumab Reduced Oral Corticosteroid Use in SUNRISE Phase 3 Trial

Key Takeaways

• Tezepelumab was associated with greater categorical maintenance oral corticosteroid reduction at week 28 than placebo in the randomized comparison.
• Over 28 weeks, 25 participants (30%) with tezepelumab and 23 participants (59%) with placebo had at least one asthma exacerbation.
• Adverse events and serious adverse events were numerically similar or lower with tezepelumab; no investigator-attributed treatment-related deaths were identified, and early termination from recruitment challenges limited interpretation.

In the SUNRISE phase 3 trial, tezepelumab was associated with greater maintenance oral corticosteroid reduction at week 28 than placebo in severe oral corticosteroid-dependent asthma, with an odds ratio of 2.93 (95% CI, 1.43-6.03; p=0.0034). Adults received blinded treatment over 28 weeks. Enrollment ended before the planned sample was reached after recruitment challenges led to early study termination and limited trial completion. The primary efficacy result favored tezepelumab for maintenance oral corticosteroid reduction while preserving asthma control at week 28 in the enrolled study population.

Across 63 sites in 12 countries, SUNRISE was a multicentre, double-blind, placebo-controlled phase 3 trial in adults with severe oral corticosteroid-dependent asthma. After oral corticosteroid optimization, adults aged 18-80 years with physician-diagnosed severe oral corticosteroid-dependent asthma entered randomization. Eligible participants had used medium-dose or high-dose inhaled corticosteroids for at least 12 months before screening. They were randomized 2:1 to tezepelumab 210 mg or placebo given subcutaneously every 4 weeks for 28 weeks, with stratification by region and blood eosinophil count. The primary outcome was the categorized percentage reduction from baseline in daily maintenance oral corticosteroid dose at week 28 while maintaining asthma control.

When the trial stopped, 122 of 207 planned participants had received treatment, including 83 assigned to tezepelumab and 39 assigned to placebo. Ninety participants completed treatment, and 25 did not complete the study because recruitment challenges led to early termination before full enrollment. Within the enrolled cohort, more participants in the tezepelumab arm reached higher categories of oral corticosteroid dose reduction by week 28 than those receiving placebo. Over the same 28-week period, fewer participants receiving tezepelumab had at least one asthma exacerbation during follow-up. The investigators interpreted the findings as showing maintenance oral corticosteroid reduction with asthma control maintained and efficacy not compromised in the enrolled population.

Safety findings were numerically similar between groups, with adverse events in 47 participants (57%) receiving tezepelumab and 28 participants (72%) receiving placebo during treatment. Serious adverse events occurred in seven participants (8%) in the tezepelumab group and five participants (13%) in the placebo group. Three deaths occurred overall, with two in the tezepelumab group during the post-treatment period and one in the placebo group during the treatment period. Investigators did not attribute any death to study treatment. The authors reported no safety concerns identified for tezepelumab in this trial.