Tezepelumab may reduce COPD exacerbations, trial data suggests
COURSE study included 337 patients
Tezepelumab, which is approved for severe asthma, tended to reduce the frequency of exacerbations in adults with moderate to very severe chronic obstructive pulmonary disease (COPD).
That’s according data from the international, proof-of-concept Phase 2a COURSE clinical trial (NCT04039113) that included 337 COPD patients irrespective of emphysema, chronic bronchitis, or smoking status. Emphysema and chronic bronchitis are distinct forms of COPD.
Data also showed significant benefits with tezepelumab relative to a placebo in subgroups of patients with high blood levels of eosinophils, a type of immune cell. High eosinophils levels are associated with type 2 inflammation, which may contribute to lung inflammation in COPD and asthma.
The findings were shared by Dave Singh, MD, the trial’s lead researcher and a professor of respiratory pharmacology at the University of Manchester, in a poster presentation at the 2024 American Thoracic Society (ATS) International Conference this week in San Diego. The poster was titled “Tezepelumab in Adults With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD): Efficacy and Safety From the Phase 2a COURSE Study.”
“With its first-in-class mechanism of action, along with the results in key subgroups from the COURSE trial, we are encouraged by the data and what it could mean for the COPD community,” Singh said in an email to COPD News Today.
“These proof-of-concept results from the COURSE trial are encouraging as they signal the potential efficacy of tezepelumab in a broad range of people with COPD irrespective of emphysema, chronic bronchitis, and smoking status,” said Sharon Barr, PhD, executive vice president, head of BioPharmaceuticals R&D at AstraZeneca, which is developing tezepelumab with Amgen, in a company press release. “As a result of these promising data, we are actively in Phase III planning for tezepelumab in COPD.”
What is tezepelumab?
COPD is marked by chronic inflammation in the lungs that blocks airflow, leading to disease symptoms such as shortness of breath, wheezing, and persistent cough.
“Despite advances in treatments for patients with COPD, there is still a pressing need for effective therapies that can improve their clinical outcome, especially for those with eosinophil counts above 150 [cell per microliter],” Jay Bradner, MD, executive vice president of Research and Development and chief scientific officer at Amgen, said in a separate press release.
Tezepelumab is a biologic therapy — meaning it’s derived from live cells — that’s approved in the U.S. and the European Union as an add-on treatment for severe asthma in people ages 12 and older. It’s sold under the name Tezspire and is a first-in-class human monoclonal antibody that blocks thymic stromal lymphopoietin (TSLP), an inflammatory molecule released by cells that line the airways in response to certain insults, such as smoke, viruses, and others. TSLP is involved in eosinophil-related and other types of airway inflammation and its release is believed to drive severe COPD exacerbations, or periods of sudden symptom worsening.
Tezepelumab in COURSE trial
The COURSE trial assessed the safety and effectiveness of tezepelumab versus a placebo in adults with moderate to very severe COPD. All the patients had received triple inhaled maintenance therapy and had at least two exacerbations in the previous year.
The participants were randomly assigned to receive an injection under the skin, or subcutaneously, of either tezepelumab (420 mg) or a placebo, once every four weeks for 52 weeks. After treatment, patients were followed for 12 weeks, or about three months.
The results of the completed trial showed that, by the end of the treatment, tezepelumab led to a 17% reduction in the annual rate of moderate or severe exacerbations compared with the placebo. The difference failed to reach statistical significance, however.
The researchers also analyzed data according to patients’ eosinophils counts. A total of 137 patients had fewer than 150 eosinophils per microliter (uL) of blood and were included in group 1; 196 patients had 150 or more cells/uL and made group 2; and 56 patients had 300 or more cells/uL and formed group 3.
Tezepelumab led to a significant reduction, by 37%, in the rate of moderate or severe exacerbations relative to a placebo in the group 2 patients. In those with the highest eosinophil counts, the therapy was linked to a 46% greater reduction versus a placebo, but this difference didn’t reach statistical significance.
Patients in groups 2 and 3 also showed greater benefits with tezepelumab regarding lung function and health-related quality of life.
The safety and tolerability profile for tezepelumab was consistent with its known profile in people with severe asthma. The most frequently reported adverse events were COPD worsening (12.1%) and COVID-19 infection (14.5%). The trial started before the height of the COVID-19 pandemic, in July 2019.
“We’re only just beginning to learn more about the mechanisms driving severe COPD. We expect biologics to play a key role and baseline eosinophil levels are a key factor in how physicians select optimal treatments for COPD,” Singh told COPD News Today. “Evidence from the COURSE trial signals the potential efficacy of tezepelumab to play a role in a broad range of people with COPD in the future, similar to its effect in severe asthma.”
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