Subgroup analysis: AIRLEAF® Phase II study of a cathepsin C (CatC, or DPP1) inhibitor, BI 1291583, in adults with non–cystic fibrosis bronchiectasis

<bold>Background:</bold> AIRLEAF^®, a Phase II study, evaluated the efficacy, safety and optimal dosing of the CatC inhibitor BI 1291583 in adults with bronchiectasis.¹ BI 1291583 treatment reduced the risk of experiencing a pulmonary exacerbation (PEx), most notably with the 2.5 mg dose, the dose taken forward into the Phase III AIRTIVITY^® study. <bold>Methods:</bold> This double-blind, placebo-controlled study randomised 322 participants to BI 1291583 (1/2.5/5 mg) or placebo for up to 48 weeks. The subgroups evaluated here are 1 PEx with SGRQ Symptoms score >40 vs ≥2 PExs in the year prior to screening, baseline <italic>P. aeruginosa</italic> status, maintenance use of macrolides at baseline and aetiology (idiopathic/post-infectious vs all others). <bold>Results:</bold> All subgroups in the 2.5 mg dose group had reductions in risk and rate of PExs consistent with the overall study population (Table 1). Hazard ratios ranged from 0.47 to 0.82, illustrating consistent prolongation of time to first PEx. Particularly, estimates of benefit for unique populations included in AIRLEAF^®, such as 1 PEx plus high symptom score, were consistent with the overall population. <bold>Conclusion:</bold> These results support the use of the 2.5 mg dose across all subgroups in AIRTIVITY^®. ¹Chalmers JD <italic>et al.</italic> Eur Respir J 2025; 65:2401551 <bold>Table 1.</bold> Subgroup analyses of risk and rate of PExs up to 48 weeks in the 2.5 mg dose group vs placebo <fig><object-id>erj;66/suppl_69/PA4959/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>