Intas Pharmaceuticals Ltd. (Biopharma), Plot No: 423/P/A, Sarkhej-Bavla Highway, Moraiya, Sanand, Ahmedabad, Gujarat, 382213, India.
Lambda Therapeutic Research Ltd., Lambda House, Plot No. 38, Survey No. 388, Near Silver Oak Club, S. G. Highway, Gota, Ahmedabad, Gujarat, 382481, India.
Clin Drug Investig. 2021 Jan;41(1):29-42. doi: 10.1007/s40261-020-00987-3. Epub 2020 Nov 24.
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.
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) and maximum measured serum concentration (C) of pegfilgrastim and area under the absolute neutrophil count (ANC) versus time curve from time zero to t (AUEC) and maximum measured ANC (E) 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.
The primary PK endpoints [AUC (90% CI 108.59-123.11) and C (106.24-118.99)] and the primary PD endpoints [AUEC (99.07-102.32) and E (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.
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.
INTP5 是一种培格非格司亭生物类似药。一项单剂量、交叉研究比较了 INTP5（培格非格司亭生物类似药）与参照药物培格非格司亭（Neulasta，培格非格司亭参照药）的药代动力学和药效学（PK/PD），一项多剂量、平行组研究比较了 INTP5 与培格非格司亭参照药在健康受试者中的免疫原性，这是完整临床开发计划的一部分。
在 PK/PD 研究中，受试者接受单次皮下 6mg 剂量的 INTP5 和培格非格司亭参照药（N=142），两者之间有 6 周的洗脱期。主要终点是从零时到无穷大（AUC）测量的血清浓度-时间曲线下面积和培格非格司亭的最大测量血清浓度（C），以及从零时到基线未调整 ANC 的时间（AUEC）的绝对中性粒细胞计数（ANC）和最大测量 ANC（E）。在免疫原性研究中，受试者接受两次 6mg 剂量的 INTP5（N=100）或培格非格司亭参照药（N=100），两者之间间隔 21 天。主要终点是两组治疗中抗药物抗体（ADA）的发生率。
主要 PK 终点[AUC（90%CI 108.59-123.11）和 C（106.24-118.99）]和主要 PD 终点[AUEC（99.07-102.32）和 E（100.24-104.25）]符合 80-125%的接受标准。INTP5 组 ADA 发生率为 10.6%，培格非格司亭参照药组为 9.0%。INTP5 和培格非格司亭参照药 ADA 发生率的风险差异 90%CI 为 1.64%（-5.40 至 8.68），在 10%的范围内。没有中和抗体的报告。免疫原性没有影响 PK/PD 参数，PK/PD 异常和安全性异常的受试者没有出现免疫原性问题。两项研究中 INTP5 和培格非格司亭参照药的不良事件（AE）发生率相似。最常见的 AE 是肌肉骨骼疼痛和头痛。
单次给药后，INTP5 与培格非格司亭参照药表现出 PK/PD 等效性，多次给药后免疫反应无临床意义差异，安全性特征相似。
