Biosimilarity of HS-20090 to Denosumab in healthy Chinese subjects: a randomized, double-blinded, pharmacokinetics/pharmacodynamics study

Objective: HS-20090 is a proposed biosimilar candidate of Denosumab (Xgeva (R)). The study aimed to evaluate the similarity of pharmacokinetics (PK), pharmacodynamics (PD), safety, and immunogenicity between HS-20090 and Xgeva (R) in healthy Chinese subjects. Methods: A single-center, randomized, double-blinded, active-controlled study was conducted in healthy Chinese adult male subjects. A total of 154 subjects were planned to be randomly assigned (1:1) to receive 120 mg of either HS-20090 or Xgeva (R) in a single subcutaneous injection, with a follow-up period of 155 days. The primary objective was to evaluate the bioequivalence of PK. The primary endpoints were C-max and AUC(0-)(infinity). The secondary objectives were to evaluate the similarity of PD, safety, and immunogenicity. Results: All 154 subjects were included in the PK, PD, and safety analyses. The 90% Cls of GMRs of HS20090/Xgeva (R) for C-max, AUC(0-t), and AUC(0-infinity) were 90.49 similar to 100.23%, 94.45 similar to 104.61%, and 94.08 similar to 105.23%, respectively, achieving the bioequivalence criteria of 80 similar to 125%. The PD parameters and incidence of adverse events between HS-20090 and denosumab were also similar, with no detection of ADA in both the groups. Conclusion: HS-20090 was highly similar to Xgeva (R), with regard to PK, PD, safety profiles, and immunogenicity in healthy Chinese subjects. These data support subsequently comparative clinical study for bone metastases in solid tumors.