Sustained Efficacy of Depemokimab Over Time in Type 2 Asthma Characterized by Blood Eosinophils: Pooled Data from the Phase III SWIFT-1/2 Studies

Abstract Rationale: Depemokimab is the first ultra-long-acting biologic engineered with enhanced interleukin-5 binding affinity, high inhibition potency, and an extended half-life, enabling twice-yearly dosing in patients with asthma. In the Phase III SWIFT-1/2 studies, depemokimab treatment significantly reduced the annualized exacerbation rate by 54% with sustained inhibition of type 2 inflammation observed in patients with type 2 asthma characterized by blood eosinophils.1 The reduced dosing schedule offered by depemokimab may alleviate treatment burden; these pooled analyses of the SWIFT-1/2 studies explore how depemokimab efficacy is maintained over the extended dosing interval. Methods: Patients with asthma and blood eosinophil counts ≥150 cells/µl at screening or ≥300 cells/µl in the past year receiving medium-to-high dose inhaled corticosteroids were randomized 2:1 to receive depemokimab 100 mg subcutaneous or placebo every 26 weeks for 52 weeks.Patients with any baseline Asthma Control Questionnaire-5 score were eligible. Prespecified secondary endpoints included change from baseline to Week 52 in total St George's Respiratory Questionnaire (SGRQ); prespecified other endpoints included time to first exacerbation. No multiplicity adjustments were performed in these pooled analyses. Results: Full analysis populations for the SWIFT-1/2 studies included 762 patients (depemokimab, n=502; placebo, n=260). Mean (standard error) change from baseline in total SGRQ score was numerically greater for depemokimab versus placebo at Week 4 (-10.79 [0.669] vs -8.02 [0.928]) and was maintained at Weeks 26 (-11.94 [0.763] vs -9.73 [1.054]) and 52 (-13.92 [0.758] vs -11.04 [1.055]; Figure A). This finding was consistent across the individual domains, which constitute SGRQ total score (i.e., symptoms, activity, and impacts) and sustained over time. The probability of experiencing an exacerbation with depemokimab was lower than with placebo by Week 4. This difference was maintained through Week 52, with no increased exacerbation risk observed in the weeks prior to dosing at Week 26 and 52 (Figure B). The probability of having an exacerbation (95% confidence interval [CI]) over 52 weeks was 32% (28%, 37%) with depemokimab and 49% (43%, 55%) with placebo (hazard ratio [95% CI] 0.54 [0.43, 0.69]).Conclusions: Twice-yearly depemokimab treatment was associated with numerically greater benefits compared with placebo, sustained over the depemokimab dosing interval, in overall health and risk of exacerbations in patients with type 2 asthma. The finding of this pooled analysis of the SWIFT-1/2 studies supports the sustained inhibition of type 2 inflammation by depemokimab. Reference: 1. Jackson DJ et al. NEJM 2024;10.1056/NEJMoa2406673.