Inderjeet Singh1, Anshul Attrey2, Adarsh Garg2, Ronak Patel2, Vinu Jose3. 1. Intas Pharmaceuticals Ltd. (Biopharma), Plot No: 423/P/A, Sarkhej-Bavla Highway, Moraiya, Sanand, Ahmedabad, Gujarat, 382213, India. 2. Lambda Therapeutic Research Ltd., Lambda House, Plot No. 38, Survey No. 388, Near Silver Oak Club, S. G. Highway, Gota, Ahmedabad, Gujarat, 382481, India. 3. Intas Pharmaceuticals Ltd. (Biopharma), Plot No: 423/P/A, Sarkhej-Bavla Highway, Moraiya, Sanand, Ahmedabad, Gujarat, 382213, India. vinu_jose@intaspharma.com.
Abstract
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.
RCT Entities:
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.
Authors: Lyndsay N Harris; Nofisat Ismaila; Lisa M McShane; Fabrice Andre; Deborah E Collyar; Ana M Gonzalez-Angulo; Elizabeth H Hammond; Nicole M Kuderer; Minetta C Liu; Robert G Mennel; Catherine Van Poznak; Robert C Bast; Daniel F Hayes Journal: J Clin Oncol Date: 2016-02-08 Impact factor: 44.544
Authors: Martine Piccart-Gebhart; Eileen Holmes; José Baselga; Evandro de Azambuja; Amylou C Dueck; Giuseppe Viale; Jo Anne Zujewski; Aron Goldhirsch; Alison Armour; Kathleen I Pritchard; Ann E McCullough; Stella Dolci; Eleanor McFadden; Andrew P Holmes; Liu Tonghua; Holger Eidtmann; Phuong Dinh; Serena Di Cosimo; Nadia Harbeck; Sergei Tjulandin; Young-Hyuck Im; Chiun-Sheng Huang; Véronique Diéras; David W Hillman; Antonio C Wolff; Christian Jackisch; Istvan Lang; Michael Untch; Ian Smith; Frances Boyle; Binghe Xu; Henry Gomez; Thomas Suter; Richard D Gelber; Edith A Perez Journal: J Clin Oncol Date: 2015-11-23 Impact factor: 44.544