Twice-Yearly Depemokimab Demonstrates Efficacy in Patients With Asthma in China and Japan: Subpopulation Analyses of the SWIFT-1/2 Studies

Abstract Rationale: Depemokimab is the first ultra-long-acting biologic with enhanced interleukin-5 binding affinity, high potency, and an extended half-life, enabling twice-yearly dosing in patients with asthma. In the Phase III SWIFT-1/2 studies, depemokimab significantly reduced asthma exacerbations by 54% with sustained inhibition of type 2 inflammation observed in patients with type 2 asthma characterized by blood eosinophils.1 Biologic availability and other treatment patterns vary regionally; as such, prespecified analyses in the SWIFT-1/2 studies assessed efficacy and safety in China and Japan subpopulations and Asia versus rest of world (ROW) subgroups. Methods: Patients with asthma, blood eosinophil count (BEC) ≥150 cells/µL (screening) or ≥300 cells/µL (past year) and ≥2 exacerbations in past year were randomized 2:1 to receive either depemokimab 100 mg subcutaneously or placebo every 26 weeks, plus standard of care, over 52 weeks. Primary endpoint was annualized exacerbation rate. Secondary endpoints included change from baseline to Week 52 in St George's Respiratory Questionnaire (SGRQ) score, Asthma Control Questionnaire-5 (ACQ-5), and prebronchodilator forced expiratory volume in 1 second (FEV1). Efficacy and safety were also assessed in patients recruited from China in SWIFT-1 and Japan in SWIFT-2 and pooled Asia versus ROW subgroups. Results: Mean asthma duration was 14.1 years in China (n=58) and 20.6 years in Japan (n=59). Baseline geometric mean BEC was 293/371 cells/µL for depemokimab/placebo, respectively, in China, and 583/459 cells/µL in Japan. Efficacy by subpopulation/globally is summarized in the Table. Depemokimab was associated with reduced exacerbation rate versus placebo in both, with percentage reductions of 85% (China) and 51% (Japan) (Table). Depemokimab-treated patients in China had a numerically greater exacerbation reduction than the SWIFT-1/2 global population, possibly reflecting a more biologic-naïve population or other contributing factors. Treatment difference (95% confidence interval [CI]) in SGRQ and ACQ-5 change from baseline at Week 52 (depemokimab vs placebo) was -9.60 (-19.57, 0.38) and -0.28 (-0.78, 0.23) in China and -8.30 (-17.39, 0.79) and -0.28 (-0.80, 0.24) in Japan (Table). Overall, there was a 65% (95% CI: 40%, 79%) exacerbation reduction in patients in Asia (n=130) versus 50% (95% CI: 35%, 62%) in ROW (n=631). Adverse event reporting was similar across depemokimab/placebo groups; 100%/90% and 88%/94% of patients experienced an adverse event in China and Japan, respectively. Conclusions: Twice-yearly depemokimab improves outcomes in patients with type 2 asthma in China, Japan, and Asia overall. Reference: 1. Jackson DJ et al. NEJM 2024;10.1056/NEJMoa2406673.