Late Breaking Abstract - Astegolimab, an anti-ST2, in chronic obstructive pulmonary disease - COPD-ST2OP: a phase IIa, placebo-controlled trial

<b>Background:</b> Chronic obstructive pulmonary disease (COPD) is a heterogeneous inflammatory airways disease. The epithelial-derived ‘alarmin’ IL-33 and its receptor ST2 have been implicated in airway inflammation and infection. We sought to determine whether astegolimab, a selective ST2 IgG2 monoclonal antibody, reduces exacerbations in COPD. <b>Methods:</b> We undertook a single-centre, randomised, double-blinded, placebo-controlled, phase IIa trial in moderate-to-very severe COPD. Participants received astegolimab 490mg (n=42) or placebo (n=39), every 4 weeks over 44 weeks. Primary endpoint was exacerbation rate over 48 weeks with pre-specified subgroup analysis by baseline blood eosinophil count. Secondary endpoints included Saint George’s Respiratory Questionnaire for COPD (SGRQ-C), FEV1, blood and sputum cell counts, and safety and tolerability. <b>Results:</b> The 48-week exacerbation rate in the astegolimab group relative to placebo was 0.78 (0.53 -0 1.14; p=0.195) in the whole group and 0.69 (0.39 - 1.21) and 0.83 (0.49 - 1.40) in subjects below or above the median baseline blood eosinophil count (170 cells/µL). In the astegolimab group versus placebo the mean difference for SGRQ-C and FEV1&nbsp;was –3.3 (-6.4 to -0.2; p=0.039) and 40ml (-10 to 90; p=0.094), respectively. The differences in geometric mean ratios for blood and sputum eosinophil counts were 0.59 (0.51&nbsp;- 0.69; p&lt;0.001) and 0.25 (0.19&nbsp;- 0.33; p&lt;0.001). Incidence of treatment-emergent adverse events was similar between groups. <b>Conclusion:</b> Astegolimab did not reduce 48-week COPD exacerbation rate significantly in the whole group,&nbsp;subgroup analyses suggested more benefit in subjects with lower blood&nbsp;eosinophil counts.