Safety and efficacy of astegolimab for COPD with frequent exacerbations regardless of baseline blood eosinophil counts (ALIENTO and ARNASA): randomised, double-blind, placebo-controlled, phase 2b and 3 trials
Astegolimab for COPD with frequent exacerbations
Targeting the ST2/IL-33 pathway in COPD
Interleukin-33 and its receptor, ST2, are implicated in neutrophilic and eosinophilic inflammation during chronic obstructive pulmonary disease (COPD) exacerbations.
We aimed to assess the efficacy and safety of astegolimab, an anti-ST2 human IgG2 monoclonal antibody, which were evaluated in two COPD pivotal trials.
ALIENTO and ARNASA trials
In two randomised, double-blind, placebo-controlled trials (phase 2b ALIENTO and phase 3 ARNASA), current or former smokers with COPD and a history of frequent exacerbations, irrespective of baseline blood eosinophils, were randomly assigned (1:1:1; stratification by smoking status and region) to receive subcutaneous astegolimab 476 mg every 2 weeks, every 4 weeks, or placebo, alongside optimised inhaled maintenance therapy over 52 weeks. The primary endpoint (analysed in participants receiving one or more doses) was annualised rate of moderate or severe exacerbations.
Astegolimab and COPD exacerbation rates
Adjusted rate ratios versus placebo for the primary endpoint were 0·85 (95% CI 0·72–1·00; p=0·049) for astegolimab every 2 weeks and 0·93 (0·79–1·10; p=0·38) for astegolimab every 4 weeks in ALIENTO, and 0·85 (0·72–1·01; p=0·068) for astegolimab every 2 weeks and 0·82 (0·70–0·98; p=0·024) for astegolimab every 4 weeks in ARNASA.
Astegolimab and the ST2/IL-33 pathway
In ALIENTO, astegolimab every 2 weeks was associated with a lower annual rate of exacerbations versus placebo in patients with COPD and a history of frequent exacerbations.
In ARNASA, these findings did not meet statistical significance. Together, these findings suggest a role for targeting the ST2/IL-33 pathway to reduce the frequency of COPD exacerbations in patients with limited treatment options.
Authors
Alberto Papi, Neil J Greening, Surya P Bhatt, Nicolas Roche, Bartolome Celli, Jadwiga A Wedzicha, Àlvar Agustí, Ruth Tal-Singer, MeiLan K Han, Wim Janssens, Nicola A Hanania, Parameswaran Nair, Peter Bremner, Konstantinos Porpodis, Yoko Shibata, Stephanie Korn, Ting Yang, Oliver Gordon, Rebecca Saenz, Julie Ng, Dorothy S Cheung, Jacob Devine, Michele A Grimbaldeston, Wenhui Zhang, Xiaoying Yang, Divya Mohan, Claus F Vogelmeier, Christopher E Brightling, on behalf of the ALIENTO and ARNASA investigators
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Fecha de publicación
May 23, 2026 — Publication date.
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