Phase I, single-dose study to compare pharmacokinetics of depemokimab delivered by safety syringe device or autoinjector in healthy adults

<bold>Background:</bold> Depemokimab is the first and only humanised anti-IL-5 antibody with enhanced binding affinity and high potency, resulting in an extended half-life, enabling 6-monthly dosing and sustained inhibition of broad inflammatory function. <bold>Aim:</bold> Compare pharmacokinetics (PK), immunogenicity and safety of depemokimab administered by safety syringe device (SSD) or autoinjector (AI). <bold>Methods:</bold> Participants randomised (1:1) received single-dose depemokimab 100 mg subcutaneously via SSD or AI, in the upper arm, abdomen or thigh (randomised 1:1:1). PK parameters were assessed up to Day 183 post dose and relative bioavailability calculated by AI:SSD geometric mean ratio (GMR). Immunogenicity (presence of anti-drug antibodies) and adverse events (AEs) were also assessed. <bold>Results:</bold> Each arm included 70 participants. PK was similar between devices. AI:SSD adjusted GMR and 90% CIs were within the bioequivalence range of 0.8 to 1.25 for C_max (1.03 [0.96, 1.09]) and AUC(_0-inf) (1.03 [0.96, 1.10]). When pooled across devices, depemokimab geometric mean (log SD) C_max (µg/mL) and AUC_0-inf (µg*day/mL) was 14.1 (0.25) and 1004.4 (0.30) for upper arm, 15.3 (0.22) and 1119.3 (0.22) for abdomen and 15.2 (0.23) and 1091.0 (0.28) for thigh, respectively. Immunogenicity incidence was low (1%) for both devices. Drug-related AE incidence was 19% (SSD) and 20% (AI). <bold>Conclusions:</bold> For single-dose depemokimab, PK and bioavailability were similar for SSD and AI; criteria for bioequivalence were met. PK was generally comparable across injection sites. Incidence of immunogenicity and AEs were low and similar for SSD and AI. <bold>Funding:</bold> GSK (214099, <ext-link>NCT05602025</ext-link>)