Pharmacokinetics and pharmacodynamics of the proposed biosimilar denosumab GP2411 and reference denosumab in healthy males

Background: This Phase I study compared the pharmacokinetic (PK) and pharmacodynamic (PD) similarity of GP2411 proposed denosumab biosimilar to reference denosumab (a monoclonal antibody for specific pro-resorptive conditions). Research design and methods: Healthy males (28-65 years, 50-90 kg) were randomized to a single sub-therapeutic subcutaneous injection of 35 mg GP2411, EU-Xgeva (R) or US-Xgeva (R), and followed for 39 weeks. The primary endpoints were AUC(inf), AUC(last), and C-max. Results: Four hundred ninety-two participants completed treatment. The 90% confidence intervals (CIs) (AUC(inf), AUC(last), and C-max) and 95% CI of the geometric mean ratios of AUEC of % change from baseline in serum CTX were fully contained within the prespecified equivalence margins (0.80, 1.25), demonstrating similarity. The occurrence of treatment-emergent adverse events (TEAEs) with GP2411, EU-Xgeva (R) and US-Xgeva (R) was similar (72.9%, 76.0%, and 71.0% of participants, respectively). Most were Grade 1 or 2, <30% were treatment-related, and there was only one TEAE-related study discontinuation. Rates of positive anti-drug antibodies (ADAs) were similar (57.8%, 64.9%, and 69.1% of participants respectively), but immunogenicity was only borderline detectable and of very low magnitude. Ninety-nine percent of positive ADAs were transient. Conclusion: GP2411 demonstrated similarity with EU-Xgeva (R) and US-Xgeva (R) in PK, PD, safety, and immunogenicity in this population.