IL-33 inhibition in COPD: Astegolimab shows promising HRQoL signals in ALIENTO and ARNASA

Abstract: Astegolimab Improves HRQoL in Patients With COPD: Evaluating SGRQ-C Response in ALIENTO and ARNASA. ATS 2026, May 15–20, 2026; Orlando, Florida, USA.

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Could you describe the mechanism of action of astegolimab and the rationale for its investigation in COPD?

Astegolimab is a monoclonal antibody targeted against the ST2 receptor, which is expressed on many inflammatory cells involved in the progression of COPD and the chronic inflammation that leads to exacerbations and ongoing lung function decline. Interestingly, it involves both the Th2 pathways, including eosinophils and downstream mediators such as IL-4, IL-13, and IL-5, as well as the Th1 pathways, which are associated with neutrophil-type inflammation. That is particularly appealing in COPD, which involves both of these inflammatory pathways.

Could you give a brief overview of the methodology of the ALIENTO and ARNASA trials, and the objectives of your health-related quality of life analysis?

They were both registration-level trials in which patients were randomized to receive astegolimab 476 mg subcutaneously either every 2 weeks or every 4 weeks, or placebo, for 52 weeks. The trials were relatively inclusive, including patients with both high and low eosinophil levels, patients with and without chronic bronchitis, and patients independent of smoking status. They also included patients with fairly severe lung function deficits, down to an FEV1 of 20% predicted. The primary outcome was the annualized rate of exacerbations. Other secondary endpoints included the endpoint of interest described in this abstract, the SGRQ-C questionnaire.

At the conference, other investigators will be presenting the primary outcomes, the exacerbation outcomes, and a top-line view of the secondary outcomes. In this analysis, we dug a little deeper into the SGRQ-C responses, specifically absolute change and the proportion of patients with a meaningful change. A post-hoc analysis of SGRQ-C subdomain scores was also performed.

What were the key findings from your analysis?

Notably, while the change in SGRQ-C was not statistically significant in either ALIENTO or ARNASA, it followed a similar pattern of an early numerical response that remained more stable than placebo throughout the 52 weeks of the trial. It involved an average improvement of just over 1 point. Again, in a pooled analysis, it showed similar results: not statistically significant in the mean response, but consistently numerically favorable throughout the 52 weeks.

Importantly, the placebo group had a fairly significant response. While the active treatment arms had important levels of response in and of themselves compared with the placebo arm, the differences were not of a magnitude that resulted in statistical significance because the placebo group tended to have a fairly strong response in this trial.

In addition to the mean response, we looked at the different domains of the SGRQ-C and, interestingly, the symptom domain seemed to drive the overall SGRQ-C response. Numerically, the symptom domain appeared to be the most responsive and showed the greatest separation from placebo. When we looked at the proportion of responders, meaning those who had at least a 4-point response, while it was not statistically significant in the ALIENTO trial, in ARNASA it did reach nominal significance, with a p-value of less than 0.01. In the pooled analysis, it was also significant, with a significantly greater proportion of patients who received astegolimab every 2 weeks having an important response in SGRQ-C compared with the placebo arm, and we found that very interesting.

Finally, we looked at the forest plot of the subgroups, and the shift in SGRQ-C relative to placebo was in the right direction across all levels of lung function severity, all levels of eosinophils, independent of smoking status, and regardless of whether patients had chronic bronchitis. All subgroups trended in the direction favoring astegolimab. So there appears to be a signal here in the SGRQ-C and quality-of-life measures across different dimensions.

What will be the next steps in the clinical development of astegolimab?

While ALIENTO met statistical significance for the primary outcome, unfortunately the ARNASA trial did not reach statistical significance regarding the annualized rate of exacerbations. There are certainly many signals showing some potential benefit of this medication in our population, but the company needs to decide with the FDA whether there is enough evidence to move forward or whether another pivotal trial would be needed to confirm the positive result seen in ALIENTO.

I think this trial does add evidence supporting the IL-33 pathway as being meaningful. I think the results we presented today are clinically meaningful to patients, and it is a matter of whether additional pivotal trial data will be needed to convince the FDA to move this drug forward.