Int J Clin Pharmacol Ther. 2022 Jun;60(6):280-290. doi: 10.5414/CP204211.
To compare the pharmacokinetics (PK), safety, tolerability, and immunogenicity of single intravenous doses of FKB238, a proposed biosimilar of bevacizumab, with European Union (EU)-approved and United States (US)-licensed bevacizumab in healthy participants.
In a randomized, double-blind, parallel-group study, 99 healthy men received 5 mg of FKB238, EU-bevacizumab, or US-bevacizumab in a 1 : 1 : 1 ratio by intravenous infusion. PK, immunogenicity, adverse events, local tolerability, vital signs, electrocardiogram, and safety tests of blood and urine were assessed before and up to 99 days after treatment.
The 90% confidence interval for the ratios of the primary (area under the curve ((AUC) and AUC) and secondary (maximum concentration (C) and elimination half-life (T)) geometric mean PK parameters were entirely within the acceptance range for bioequivalence of 0.80 - 1.25 for all 3 pairwise comparisons by analysis of covariance, with baseline characteristics of age and body weight as covariates. FKB238 was well tolerated in healthy participants, and anti-drug antibody (ADA) incidence was low and similar in all treatment groups.
The study demonstrated the PK similarity of FKB238 to both EU-bevacizumab and US-bevacizumab after a single intravenous infusion. FKB238 was well tolerated in healthy participants, and there was no difference in ADA incidence among the 3 products.
比较单次静脉注射 FKB238（一种贝伐珠单抗的生物类似药）与欧盟（EU）批准和美国（US）许可的贝伐珠单抗在健康受试者中的药代动力学（PK）、安全性、耐受性和免疫原性。
在一项随机、双盲、平行组研究中，99 名健康男性以 1：1：1 的比例静脉输注 5mg 的 FKB238、EU-贝伐珠单抗或 US-贝伐珠单抗。在治疗前和治疗后 99 天内评估 PK、免疫原性、不良事件、局部耐受性、生命体征、心电图以及血液和尿液的安全性检测。
通过协方差分析，所有 3 种两两比较的主要（曲线下面积（AUC）和 AUC）和次要（最大浓度（C）和消除半衰期（T））几何均数 PK 参数的比值 90%置信区间完全在生物等效性的接受范围内（0.80-1.25），协变量为年龄和体重的基线特征。FKB238 在健康受试者中耐受性良好，且抗药物抗体（ADA）发生率低且在所有治疗组中相似。
该研究表明，单次静脉输注后，FKB238 与 EU-贝伐珠单抗和 US-贝伐珠单抗的 PK 相似。FKB238 在健康受试者中耐受性良好，且 3 种产品的 ADA 发生率无差异。
