Amgen announced the results of the Phase 2a COURSE trial evaluating Tezspire® (tezepelumab-ekko) in people with moderate to very severe chronic obstructive pulmonary disease (COPD) with a broad range of baseline blood eosinophil counts (BEC) irrespective of emphysema, chronic bronchitis or smoking status. The primary results showed that treatment with Tezspire led to a 17% numerical reduction in the annual rate of moderate or severe COPD exacerbations compared to placebo at week 52, which was not statistically significant (90% CI: -6, 36; p[1-sided]=0.1042). The results will be featured in presentations at the American Thoracic Society (ATS) International Conference, May 17-22, in San Diego.

Importantly, this proof-of-concept study showed that, in patients with BEC =150 cells/µL, tezepelumab led to a nominally significant reduction of 37% in the rate of moderate or severe exacerbations compared to placebo. Studies suggest that approximately 65% of bio-eligible patients with COPD have a BEC =150 cells/µL. Among patients with BEC =300 cells/µL, tezepelumab led to a numerical reduction of 46% in the rate of moderate or severe exacerbations (Table 1). Trends towards improved outcomes were also seen with tezepelumab use for pre-bronchodilator FEV1 and SGRQ total score.

A subgroup analysis of the COURSE trial also showed treatment with tezepelumab resulted in numerical improvements in lung function as measured by forced expiratory volume (FEV1) (improvement of 63 mL and 146 mL in BEC =150 and =300 cells/µL respectively, compared to placebo) and in quality of life as measured by the St. George's Respiratory Questionnaire (SGRQ) score (reduction of 4.2 points and 9.5 points in BEC =150 and =300 cells/µL respectively). The safety and tolerability profile for tezepelumab was consistent with its approved severe asthma indication; the most frequently reported (>10%) adverse events for tezepelumab were worsening of COPD (12.1%) and incidents of COVID-19 infections (14.5%) (this trial commenced in July 2019) (Table 2).

COURSE was a Phase 2a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial designed to evaluate the safety and efficacy of tezepelumab in adults with moderate to very severe COPD receiving triple inhaled maintenance therapy, and having had two or more documented COPD exacerbations in the 12 months prior to Visit 1. A total of 337 patients were randomized globally, with patients stratified by region and prior number of exacerbations (two vs. three or more). Patients received tezepelumab 420 mg or placebo administered via subcutaneous injection at the trial site every four weeks over a 52-week treatment period.

The trial included a post-treatment follow-up period of 12 weeks. COPD refers to a group of lung diseases, including chronic bronchitis and emphysema, that cause airflow blockage and breathing-related problems. COPD is a major public health threat that affects an estimated 391 million people around the world, with global costs connected to the disease expected to rise to US $4.8 trillion by 2030. COPD is a highly complex disease with multiple pathways and disease drivers, and a single COPD exacerbation can increase the risk of hospitalization.

Baseline blood eosinophil counts are a key factor in how physicians select optimal treatments for COPD. Approximately 65% of patients with COPD who are eligible for biologic treatment have a BEC >150 cells/µL, 20-40% have a BEC >300 cells/µL.