Two international clinical trials led in part by researchers at the University of Pittsburgh School of Medicine found that the investigational biologic therapy tozorakimab significantly reduced chronic obstructive pulmonary disease (COPD) flare-ups among patients already receiving standard treatment for the disease compared to patients only receiving standard treatment. The findings are published today in the New England Journal of Medicine.
"Reducing exacerbations is one of the most important goals in the treatment of COPD because flare-ups have a profound impact on patients' health, quality of life and long-term outcomes," said co-lead author Frank C. Sciurba, M.D., professor of medicine in the Division of Pulmonary, Allergy, Critical Care and Sleep Medicine at Pitt. "The results of this trial suggest an important new strategy for reducing the burden of COPD exacerbations."
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease that causes breathing difficulties and usually – but not always – results from chronic smoking of tobacco. It affects hundreds of millions of people worldwide and remains one of the leading causes of death globally. Exacerbations, or flare-ups, are periods of worsening symptoms that often require additional treatment, emergency care or hospitalization.
The Phase 3 clinical trials evaluated tozorakimab, a monoclonal antibody that is given through injections under the skin. It targets interleukin-33 (IL-33), a protein involved in airway inflammation and mucus production. Across the studies, patients receiving tozorakimab experienced approximately 29% to 34% fewer moderate-to-severe COPD exacerbations than those receiving placebo. Unlike existing biologics for COPD, the effect was clinically impactful across all levels of critical blood cell called eosinophils.
More than 1,700 patients with COPD participated in the clinical trials. Participants were current or former smokers with a history of COPD exacerbations and were followed for one year while receiving either tozorakimab or placebo in addition to standard therapy. Researchers found that the reduction in exacerbations was observed across a broad COPD population, regardless of smoking status, severity of lung function impairment or blood eosinophil levels.
The studies also found that tozorakimab's overall safety profile was generally similar to placebo. Investigators reported that rates of adverse events and serious adverse events were comparable between treatment groups, with injection-site reactions occurring more frequently among patients receiving tozorakimab.
"Our study data and results will now be under consideration by the U.S. Food and Drug Administration for approval to use in qualifying patients outside of a clinical trial," said Sciurba, who is also a pulmonologist at UPMC. "It is encouraging to have an additional, safe therapy for patients who often struggle to breathe."
Henrick Watz, M.D., of the University of Luebeck in Germany, co-led the study article. Additional authors are listed in the NEJM article.
The clinical trials were sponsored and funded by AstraZeneca, the developer of tozorakimab. AstraZeneca designed and conducted the studies in collaboration with international investigators and provided support for data collection and analysis.
