Regional Variation in Response to Depemokimab (Depe) vs Placebo (Pbo) in Patients (Pts) With Asthma With Type 2 (T2) Inflammation: Subgroup Analyses of the Phase III SWIFT-1/2 Studies

Rationale: In several trialsof asthma therapies, regional variation in magnitude of Pbo response has been seen, possibly reflecting differences in healthcare system structures. Depe is the first ultralong-acting biologic with enhanced IL-5 binding affinity, high potency, and an extended half-life, enabling twice-yearly dosing in asthma pts. In the Phase III SWIFT-1/2 studies, Depe significantly reduced exacerbations with sustained inhibition of T2 inflammation in pts with T2 asthma characterized by blood eosinophils. Post hoc analyses of regional variations were conducted to explore impact of regional variation on overall SWIFT-1/2 results. Methods: Prespecified and post hoc analyses of SWIFT-1/2 studies were conducted to investigate annualized exacerbation rates and change from baseline to Wk 52 in St George’s Respiratory Questionnaire (SGRQ) score by region. Results: Pts (N=762) across 16 countries in SWIFT-1/2, had a mean (SD) of 2.4 (1.46) exacerbations in the past year. In a prespecified subgroup analysis, exacerbation rate reduction in pts treated with Depe vs Pbo was broadly consistent across pts in Europe, USA, and Rest of World (ROW). In post hoc analyses, numerically lower exacerbation rate reductions (95% CI) were observed in pts in Central East Europe vs West Europe, USA, and ROW, and Poland vs ROW, driven by low exacerbation rates in the Pbo arm in Central East Europe (Depe: 0.50 [0.37–0.69] vs Pbo: 0.66 [0.44–0.99]) and Poland (Depe: 0.33 [0.22–0.51] vs Pbo: 0.34 [0.18–0.62]). In ROW (excluding Poland) exacerbation rates were 0.55 (0.47–0.66) vs 1.30 (1.07–1.58) for Depe vs Pbo. Similar Pbo response patterns were observed for change from baseline in SGRQ at Week 52. Conclusions: Twice-yearly Depe efficacy in the SWIFT-1/2 trials was broadly consistent across regions. However, differential exacerbation reduction was observed among pts in Central East Europe, where there was a substantial Pbo response, vs other regions. This could reflect variation in clinical practice and adherence to background therapies prior to trial initiation. Regional differences in treatment response could also be due to biologic access (eg, due to stopping rules/reimbursement criteria), leading to differences in pt populations entering clinical trials over time. Previously presented at the ERS (2025) Congress; Amsterdam, Netherlands; September 27 to October 1, 2025. Fig. 1 Publication History Article published online: 04 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany