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The following is a summary of “Efficacy and safety of tezepelumab versus placebo in adults with moderate to very severe chronic obstructive pulmonary disease (COURSE): a randomised, placebo-controlled, phase 2a trial,” published in the January 2025 issue of Pulmonology by Singh et al. 

Tezepelumab, a human monoclonal antibody targeting thymic stromal lymphopoietin, has shown elevated expression in individuals with chronic obstructive pulmonary disease (COPD) compared to healthy individuals. 

Researchers conducted a retrospective study to assess the efficacy and safety of Tezepelumab in patients with moderate to very severe COPD despite receiving triple inhaled therapy. 

They performed a phase 2a trial (COURSE) across 90 sites in 10 countries (Asia, Europe, and North America). Eligible participants were aged 40–80 years with moderate to very severe airflow limitation, receiving triple inhaled therapy, and had ≥2 moderate to severe COPD exacerbations in the past 12 months. Participants were randomly assigned (1:1) to receive either 420 mg tezepelumab or placebo subcutaneously every 4 weeks for up to 52 weeks. Randomization was stratified by geographical region and exacerbation history. Treatment assignment was masked to participants, investigators, site staff, and sponsors. The primary endpoint was the annualized rate of moderate or severe COPD exacerbations over 52 weeks, with a prespecified subgroup analysis based on baseline blood eosinophil counts (BECs). Efficacy and safety were assessed in patients who received at least 1 dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04039113 (completed). 

The results showed that between July 30, 2019, and Oct 4, 2022, 333 patients (mean age 67.2 years [SD 7.0]; 44% female, 56% male; 88% White, 10% Asian, 1% Black or African American) were randomly assigned to receive either tezepelumab (n = 165) or placebo (n = 168). The annualized rate of moderate or severe COPD exacerbations over 52 weeks was 1.75 for tezepelumab vs 2.11 for placebo (rate ratio 0.83 [90% CI 0.64–1.06]; P = 0.10 [one-sided]; primary endpoint not met). In subgroup analyses, the annualized rate of exacerbations was 2.04 with tezepelumab vs 1.71 with placebo (rate ratio 1.19 [95% CI 0.75–1.90]) for baseline BEC <150 cells/μL, 1.64 vs 2.47 (rate ratio 0.66 [95% CI 0.42–1.04]) for BEC 150–299 cells/μL, and 1.20 vs 2.24 (rate ratio 0.54 [95% CI 0.25–1.15]) for BEC ≥300 cells/μL. Adverse events were reported in 81% of patients in the tezepelumab group and 75% in the placebo group. Serious adverse events occurred in 30% of both groups and 5 patients died during the study (2 in the tezepelumab group and 3 in the placebo group), with no deaths deemed related to the treatment by the investigators. 

Investigators concluded the tezepelumab did not significantly reduced the annualised rate of moderate or severe COPD exacerbations compared to placebo, and further studies were needed to assess its efficacy in patients with baseline BEC ≥150 cells/μL, with no safety concerns identified. 

Source: thelancet.com/journals/lanres/article/PIIS2213-2600(24)00324-2/abstract