Tezepelumab Reduces Rate of COPD Exacerbations in Individuals with Wide Range of Blood Eosinophil Levels: Phase 2a COURSE Trial Findings

Treatment with tezepelumab in adults with moderate to very severe chronic obstructive pulmonary disease (COPD) was not able to achieve a statistically significant reduction in the annual rate of moderate to severe COPD exacerbations, the primary endpoint of the phase 2a COURSE trial, compared to placebo. The thymic stromal lymphopoietin (TSLP) inhibitor was successful, however, in reducing the exacerbation rate in subgroups of study participants with blood eosinophil count (BEC) levels of 150 cells/µL or greater.

The findings were presented during a late-breaking abstract session at the 2024 American Thoracic Society International Conference, May 17-22, 2024, in San Diego, CA, and announced by codevelopers AstraZeneca and Amgen.

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Compared to placebo, tezepelumab led to a 17% numerical reduction in the annual rate of moderate or severe disease exacerbations compared to placebo at 52 weeks in the proof-of-concept trial. Adults enrolled in COURSE (N = 337) reflected a wide range of individuals with COPD, without regard for presence of emphysema, chronic bronchitis, or smoking status and with a broad range BEC levels, according to the announcement.

When COURSE trial investigators looked at response to tezepelumab by participant BEC levels, there were important differences from the overall group, with a significant reduction of exacerbations classified as moderate or severe of 37% compared to placebo among participants with BEC levels of 150 cells/µL or greater. Further, among participants with BEC levels of 300 cells/µL or more, investigators reported a reduction in the rate of exacerbations of 46%. Together the 2 groups represent a large potential population for intervention, AstraZeneca and Amgen said, citing research that suggests nearly two-thirds (65%) of individuals with COPD who are eligible for treatment with a biologic agent have BEC levels of 150 cells/µL or greater.¹

“I believe that biologics will play a critical role in the future care of COPD and trials such as the tezepelumab COURSE trial are central to understanding and shaping the treatment landscape,” lead investigator Dave Singh, MD, professor of respiratory pharmacology at the University of Manchester, Manchester, England, said in the announcement. “The tezepelumab COURSE results are particularly important as they show activity in COPD across a broad patient population including those with baseline blood eosinophil counts greater than 150 cells/μL.”¹

The salutary effects of tezepelumab extended to lung function, with numerical improvements reported in forced expiratory volume (FEV₁) of 63 mL in participants with BEC ≥150 and of 146 mL in those with BEC ≥300 cells/μL, both vs placebo, as well as in quality of life, reflected by reductions in St George’s Respiratory Questionnaire score of 4.2 points in participants with BEC ≥150 cells/μL and 9.5 points among those with BEC ≥300 cells/μL.

The 337 participants in the COURSE trial had COPD that ranged from moderate to very severe, were receiving triple inhaled maintenance therapy, and had had 2 or more documented COPD exacerbations in the 12 months leading to the first study visit, AstraZeneca said. The cohort was stratified by global region and by prior number of COPD exacerbations (2 vs 3 or more) and randomly assigned to receive either tezepelumab 460 mg, or placebo, by subcutaneous injection every 4 weeks during trial site visits over the 52-week treatment period. They were followed for a 12-week post-treatment period.¹

Tezepelumab is a first-in-class human monoclonal antibody that inhibits a primary source of inflammation in patients with severe asthma.² It targets and blocks thymic stromal lymphopoietin, or TSLP, a key epithelial cytokine that sits at the top of multiple inflammatory cascades and initiates an overreactive immune response to allergic, eosinophilic, and other types of airway inflammation associated with severe asthma.

Tezepelumab was approved by the FDA in December 2021 as add-on maintenance treatment for severe asthma and is the only biologic agent with the indication that includes no limitations for either phenotype or biomarker in the approved label.³ The safety and tolerability profile of tezepelumab during the COURSE trial “was consistent with its approved severe asthma indication.” Adverse events with reports of more than 10% were COPD worsening and incident COVID-19 (COURSE began in July 2019).¹

According to Sharon Barr, executive vice president, biopharmaceutical R&D at AstraZeneca, the proof-of-concept findings from COURSE lay the groundwork for phase 3 planning for tezepelumab in COPD.¹

1. Singh D, Bafadhel M, Brightling CE, et al, on behalf of COURSE study investigators. Tezepelumab in adults with moderate to very severe chronic obstructive pulmonary disease (COPD): efficacy and safety from the phase 2a COURSE study. Am J Resp Crit Care Med. 2024;209:A2782 https://www.atsjournals.org/doi/epdf/10.1164/ajrccm-conference.2024.209.1_MeetingAbstracts.A2782?role=tab
2. Halsey G. Tezepelumab FDA-approved for self-administration by patients with sever asthma. Patient Care. February 2, 2023. https://www.patientcareonline.com/view/tezepelumab-fda-approved-for-self-administration-with-prefilled-pen-autoinjector
3. Halsey G. FDA accepts tezepelumab biologics license application and grants priority review. Patient Care. July 8, 2021. https://www.patientcareonline.com/view/fda-accepts-tezepelumab-biologics-license-application-and-grants-priority-review