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AstraZeneca's monoclonal antibody misses primary endpoint in mid-stage trial in COPD

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AstraZeneca’s anti-IL-33 monoclonal antibody failed a Phase 2a study in chronic obstructive pulmonary disease, though the company noted there were still “encouraging clinical efficacy signals.”

In the 135-patient FRONTIER-4 trial, patients with COPD were enrolled in the small proof-of-concept study regardless of blood eosinophil counts and smoking status. They got 600 mg of AstraZeneca’s tozorakimab or placebo every four weeks for 12 weeks. The data were presented at the European Respiratory Society Congress in Vienna on Sept. 8.

The study missed the primary endpoint of improvement in pre-bronchodilator forced expiratory volume, which is the amount of air an individual can exhale during a forced breath. But AstraZeneca said there was a greater pre-bronchodilator forced expiratory volume of 59 mL versus placebo in a subset of patients.

The company also pointed out that tozorakimab numerically reduced the risk of COPDCompEx events by 36% in patients with two or more moderate or one or more severe previous exacerbations. About 41% of patients receiving tozorakimab and 64% of patients on placebo experienced a COPDCompEx event.

According to AstraZeneca, COPDCompEx is a composite exacerbation endpoint “that is suited for use in smaller and shorter Phase 2 studies to predict treatment effect on COPD exacerbations in Phase 3 trials.”

“Findings suggest that tozorakimab may improve lung function and reduces COPD worsening events, particularly in the population at high risk of future exacerbations being studied in the ongoing Phase 3 LUNA programme,” Dave Singh, the study’s lead investigator and professor of respiratory pharmacology at the University of Manchester, said in a release.

AstraZeneca said tozorakimab is still being tested in several late-stage clinical trials to see if it can reduce excess inflammation and epithelial remodeling in COPD patients. It’s also being investigated in severe viral lower respiratory tract disease.


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