A phase 2b trial published in The Lancet found that astegolimab, a monoclonal antibody targeting the ST2/IL-33 pathway, was associated with a lower annual rate of exacerbations compared with placebo in patients with chronic obstructive pulmonary disease (COPD) who have a history of frequent exacerbations. However, a parallel phase 3 trial, ARNASA, did not meet its primary endpoint of statistical significance. Together, these results suggest the drug may reduce exacerbation frequency in a subset of patients with limited treatment options.
COPD affects approximately 480 million people globally, a figure projected to rise to nearly 600 million over the next two decades. Even with maximal inhaled therapy—long-acting beta agonists, long-acting muscarinic antagonists, and inhaled corticosteroids—about one-third of patients continue to experience multiple exacerbations. The findings point to a new biologic approach for those who have few remaining options.
The ALIENTO study evaluated astegolimab dosed every two weeks. Researchers reported a statistically significant reduction in the annual exacerbation rate versus placebo. The ARNASA trial, designed to confirm these results, did not achieve statistical significance. No specific numeric results were provided in the source for either trial.
If further studies confirm efficacy, astegolimab could become the first biologic targeting the ST2/IL-33 pathway approved for COPD. This would offer a new mechanism of action beyond standard inhaled therapies. Patients with frequent exacerbations despite optimal inhaled treatment could benefit most.
The mixed results highlight the need for additional trials to identify which patients are most likely to respond. Experts caution that the phase 3 failure tempers enthusiasm, and regulatory approval remains uncertain.