LAUSR

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 (AUC 0-∞ ) and maximum measured serum concentration ( C max ) of pegfilgrastim and area under the absolute neutrophil count (ANC) versus time curve from time zero to t (AUEC 0-t ) and maximum measured ANC ( E max ) 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 [AUC 0-∞ (90% CI 108.59–123.11) and C max (106.24–118.99)] and the primary PD endpoints [AUEC 0-t (99.07–102.32) and E max (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.