Pharmacokinetics and pharmacodynamics of the denosumab biosimilar FKS518 and reference denosumab in healthy subjects: the Lumiade-1 study.

Denosumab is a fully human monoclonal antibody that increases BMD, inhibits bone resorption and reduces fracture risk. This double-blind, randomized, parallel group study aimed to demonstrate the pharmacokinetic (PK) equivalence and compare the pharmacodynamic (PD), safety and immunogenicity profiles of the proposed denosumab biosimilar FKS518 vs the originator (reference) denosumab. Healthy males (28-55 yr) were randomized to a single 60 mg s.c. injection of FKS518 or the reference denosumab (Prolia) and were followed for 40 wk after drug injection. The primary endpoints were area under the concentration-time curve (AUC) from time zero to infinity, AUC from time zero to the last quantifiable concentration, and maximum observed serum concentration. A total of 213 subjects were injected. Pharmacokinetic equivalence was demonstrated as the 90% CIs for the geometric least squares means ratio FKS518/reference denosumab for the three primary PK parameters were fully contained within the predefined bioequivalence limits. Secondary PK, PD, safety, and local tolerability endpoints also supported the similarity of FKS518 and reference denosumab. No anti-drug antibodies were detected in either treatment group. These results demonstrate that FKS518 is equivalent to originator denosumab with respect to PK profile.