AstraZeneca's COPD antibody fails mid-stage trial endpoint

AstraZeneca's anti-IL-33 monoclonal antibody, tozorakimab, did not meet the primary goal in a Phase 2a clinical study for chronic obstructive pulmonary disease (COPD), but the company highlighted some "encouraging clinical efficacy signals."

The trial, named FRONTIER-4, involved 135 patients with COPD. Participants were included regardless of their blood eosinophil counts and smoking status. They were administered 600 mg of tozorakimab or a placebo every four weeks over a 12-week period. The findings were unveiled at the European Respiratory Society Congress held in Vienna on September 8.

The study's primary endpoint was to observe an improvement in pre-bronchodilator forced expiratory volume (FEV1), which measures the volume of air exhaled during a forced breath. Unfortunately, the trial did not achieve this primary endpoint. However, a subset of patients who received tozorakimab demonstrated a greater pre-bronchodilator FEV1 of 59 mL compared to those given a placebo.

Additionally, AstraZeneca noted that tozorakimab showed a numerical reduction in the risk of COPDCompEx events by 36% in patients with a history of two or more moderate exacerbations or one or more severe exacerbations. In the study, 41% of patients on tozorakimab encountered a COPDCompEx event, compared to 64% on the placebo.

COPDCompEx is a composite endpoint combining various exacerbation criteria, designed specifically for smaller and shorter Phase 2 trials. It helps predict the treatment's effect on COPD exacerbations, which is crucial for planning Phase 3 trials.

Dave Singh, the lead investigator and a professor of respiratory pharmacology at the University of Manchester, commented that the findings indicate tozorakimab may enhance lung function and reduce the frequency of COPD worsening events. This is particularly significant for patients at high risk of future exacerbations, a group that is the focus of the ongoing Phase 3 LUNA program.

AstraZeneca is continuing to test tozorakimab in several late-stage clinical trials. These trials aim to determine whether the antibody can address excess inflammation and epithelial remodeling in COPD patients. Additionally, tozorakimab is under investigation for its potential effectiveness against severe viral lower respiratory tract diseases.