Comparison of pharmacokinetics, pharmacodynamics, safety, and immunogenicity of a candidate biosimilar INTP23.1 with EU and US‑approved denosumab reference products in healthy adult men

PURPOSE: This Phase 1 study evaluated the pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and safety of INTP23.1, a proposed denosumab biosimilar, compared with US- and EU-licensed reference denosumab (Xgeva®) in healthy male volunteers. METHODS: This randomized, double-blind, three-arm, 36 week, parallel-group trial (CTRI/2020/09/027619), assessed a single 35 mg subcutaneous dose of INTP23.1, Xgeva (US), or Xgeva (EU), administered in the upper arm. PK endpoints were statistically compared using geometric least-squares means (LSM) and 90% confidence intervals (CIs). PD markers were evaluated, immunogenicity and safety were assessed through validated assays, and adverse events (AEs) were monitored. RESULTS: A total of 234 healthy male volunteers were enrolled. Baseline demographics were similar across the three treatment sequence groups. PK equivalence was demonstrated, with all geometric LSM ratios and 90% CIs for maximum serum concentration, area under the concentration-time curve (AUC) from time zero to the last measurable concentration, and AUC from time zero to infinity falling within the predefined bioequivalence range of 80.00% to 125.00%. PD responses showed comparable suppression of C-terminal telopeptide (CTX) and procollagen type 1 N-terminal propeptide (P1NP) across treatment groups. Immunogenicity profiles were similar, with low anti-drug antibody incidence and no neutralizing antibodies detected. AEs were generally mild or moderate in intensity, and no unexpected safety signals were observed. CONCLUSIONS: INTP23.1 demonstrated comparable PK, PD, immunogenicity, and safety to US- and EU-licensed denosumab reference products in healthy male volunteers. These findings support further clinical development of INTP23.1 as a denosumab biosimilar for approved indications. TRIAL REGISTRATION NUMBER: CTRI/2020/09/027619; Registered 07/09/2020.