Evaluation of Pharmacokinetics of Lebrikizumab in Healthy Individuals After Subcutaneous Administration Using a Prefilled Syringe or Autoinjector in a Phase 1 Randomized Study

Clin Ther. 2024 Dec 4:S0149-2918(24)00323-0. doi: 10.1016/j.clinthera.2024.10.016. Online ahead of print.

Abstract

Purpose: Lebrikizumab is a novel, high-affinity immunoglobulin G4 monoclonal antibody that targets interleukin-13, a central mediator in atopic dermatitis (AD). In previous studies in patients with moderate-to-severe AD, lebrikizumab, administered subcutaneously via a prefilled syringe with a needle safety device (PFS-NSD), demonstrated rapid and durable dose-dependent efficacy. We assessed the pharmacokinetics and safety of lebrikizumab using either a PFS-NSD or an investigational autoinjector. Such devices have been developed to make self-injection easier for patients, thus increasing adherence over long treatment durations.

Methods: The current study compared the pharmacokinetics and safety of 250 mg lebrikizumab (2 mL of a 125-mg/mL solution) administered subcutaneously at 1 of 3 different injection sites (abdomen, arm, or thigh) in 241 healthy participants using either a PFS-NSD (N = 122) or an investigational autoinjector (N = 119).

Findings: Statistical analysis demonstrated 2-mL (125 mg/mL) lebrikizumab autoinjector was bioequivalent to 2-mL (125 mg/mL) lebrikizumab PFS-NSD as 90% CIs of the geometric least squares means ratios for lebrikizumab AUC(0-tlast), AUC(0-∞), and Cmax were all completely contained within the prespecified confidence limits of 0.80 and 1.25. Injection-site location did not appear to impact lebrikizumab systemic exposure for either device. Lebrikizumab was well tolerated with no SAEs reported after PFS-NSD or autoinjector administration.

Implications: Bioequivalence was demonstrated between 250 mg lebrikizumab 2-mL autoinjector and prefilled syringe devices, showing both devices to be suitable options for administering lebrikizumab.

Keywords: Atopic dermatitis; Autoinjector; Biologics; Clinical trials; Pharmacokinetics.