RESUMO
BACKGROUND AND OBJECTIVE: INTP5 has been developed as a pegfilgrastim biosimilar. Single-dose, crossover study compared the pharmacokinetics and pharmacodynamics (PK/PD) of INTP5 (pegfilgrastim biosimilar) with reference pegfilgrastim (Neulasta®, pegfilgrastim-ref) and a multiple-dose, parallel-group study compared the immunogenicity of INTP5 with pegfilgrastim-ref in healthy subjects as part of a complete clinical development plan. METHODS: In the PK/PD study, subjects received a single subcutaneous 6 mg dose of INTP5 and pegfilgrastim-ref (N = 142) separated by a 6-week washout period. The primary endpoints were area under the serum concentration-time curve measured from time zero to infinity (AUC0-∞) and maximum measured serum concentration (Cmax) of pegfilgrastim and area under the absolute neutrophil count (ANC) versus time curve from time zero to t (AUEC0-t) and maximum measured ANC (Emax) of baseline non-adjusted ANCs. In the immunogenicity study, subjects received two 6 mg doses of INTP5 (N = 100) or pegfilgrastim-ref (N = 100) separated by 21 days. The primary endpoints were incidence of anti-drug antibodies (ADAs) in the two treatment groups. RESULTS: The primary PK endpoints [AUC0-∞ (90% CI 108.59-123.11) and Cmax (106.24-118.99)] and the primary PD endpoints [AUEC0-t (99.07-102.32) and Emax (100.24-104.25)] met the acceptance criteria of 80-125%. The incidence of ADAs was 10.6% in the INTP5 arm and 9.0% in the pegfilgrastim-ref arm. The 90% CI for risk difference of the ADA incidence between INTP5 and pegfilgrastim-ref was 1.64% (- 5.40 to 8.68) and was within the 10% margin. No neutralizing antibodies were reported. Immunogenicity did not impact PK/PD parameters and subjects with aberrant PK/PD/safety did not show immunogenicity concerns. Incidence of adverse events (AEs) was similar with INTP5 and pegfilgrastim-ref in both studies. The most common AEs were musculoskeletal pain and headache. CONCLUSION: INTP5 showed PK/PD equivalence with pegfilgrastim-ref following a single dose, no clinically meaningful difference in the immune response following multiple doses, and a comparable safety profile.