Depemokimab PK/PD in the 52-week randomised double-blind multicentre phase III SWIFT-1 trial

Abstract

Prérequis/contexte

Depemokimab is the first and only humanised anti-IL-5 antibody with enhanced binding affinity and high potency, resulting in extended half-life and enabling 6-monthly dosing.

Objectifs

Investigate depemokimab pharmacokinetic (PK)/pharmacodynamic (PD) durability in patients with asthma in SWIFT-1.

Méthodes

In this phase 3A, randomized, placebo-controlled trial, we evaluated the efficacy and safety of depemokimab in patients with severe asthma and an eosinophilic phenotype characterized by a high eosinophil count (≥300 cells per microliter within the past 12 months or ≥150 cells per microliter at screening) and a history of exacerbations despite receiving medium or high-dose inhaled corticosteroids. Patients were randomly assigned in a 2: 1 ratio to receive either depemokimab (at a dose of 100 mg subcutaneously) or placebo at weeks 0 and 26, in addition to standard treatments. Pharmacokinetics and pharmacodynamics were prespecified endpoints.

Blood eosinophil counts (BEC) were loge transformed; ratio to baseline was analysed with a mixed model for repeated measures.

Résultats/discussions

Baseline geometric mean BEC was 298 cells/μL (SD logs 0.80) for depemokimab (n = 250) and 310 cells/μL (SD logs 0.84) for placebo (n = 132). Week 2 depemokimab BEC ratio to baseline was ∼5-fold lower vs placebo (0.20 vs 1.07; ratio 0.19 [95% CI 0.16, 0.21; P < 0.001]). This ∼5-fold BEC suppression was sustained to week 52 (depemokimab 0.17 vs 0.81; ratio 0.21 [95% CI 0.17, 0.26; P < 0.001]).

Conclusion

Sustained depemokimab concentration and rapid and sustained BEC suppression, reflecting inflammation biomarkers, support depemokimab as a twice-yearly option for patients with asthma.