Specialty Clinical Development, Teva Pharmaceutical Industries Ltd, Netanya, Israel.
Specialty Clinical Development Teva Branded Pharmaceutical Products R&D, West Chester, Pennsylvania, USA.
Clin Pharmacol Drug Dev. 2021 Sep;10(9):1018-1027. doi: 10.1002/cpdd.902. Epub 2021 Jan 7.
Fremanezumab (AJOVY; Teva Pharmaceutical Industries Ltd, Netanya, Israel), approved for the preventive treatment of migraine, is available as a subcutaneous injection either once a month or once every 3 months using an autoinjector or a prefilled syringe. The present study evaluated the pharmacokinetic (PK) bioequivalence of a single subcutaneous injection of fremanezumab 225 mg administered using an autoinjector compared to a prefilled syringe in healthy volunteers. Blood samples for PK and antidrug antibodies were collected before and after dosing. Safety and tolerability assessments included physical examinations, adverse event reporting, laboratory evaluations, and immunogenicity. Following single-dose administration, the mean concentration-time profiles for the 2 treatment groups (autoinjector, n = 106; and prefilled syringe, n = 110) were similar. The point estimates for the back-transformed ratio (autoinjector/prefilled syringe) of geometric least squares means of maximum plasma concentration, area under the plasma concentration-time curve from time 0 to the time of the last measurable drug concentration, and area under the plasma concentration-time curve from time 0 extrapolated to infinity were 1.03, 1.04, and 1.05, respectively, with the 90% confidence intervals entirely contained within bioequivalence margins of 0.8 to 1.25. For both groups, median time to maximum observed concentration was 5 days and mean terminal elimination half-life was approximately 29 days. Treatment-related adverse events were reported by 39 (36%) subjects in the autoinjector group and 26 (24%) in the prefilled syringe group, and the majority were nonserious injection site reactions. The incidence of treatment-emergent antidrug antibody response was low and evenly distributed between the autoinjector (n = 3; 3%) and prefilled syringe (n = 4; 4%) groups. These results indicate that the fremanezumab autoinjector presentation provides an easy-to-use bioequivalent PK profile with a similar safety and tolerability profile to that of the prefilled syringe.
依洛尤单抗（AJOVY；梯瓦制药工业有限公司，以色列耐塔尼亚），批准用于偏头痛的预防性治疗，可通过皮下注射，每月一次或每三个月一次，使用自动注射器或预充注射器。本研究评估了健康志愿者单次皮下注射依洛尤单抗 225mg 后，使用自动注射器与预充注射器的药代动力学（PK）生物等效性。在给药前后采集用于 PK 和抗药物抗体的血样。安全性和耐受性评估包括体格检查、不良事件报告、实验室评估和免疫原性。单次给药后，2 种治疗组（自动注射器，n=106；预充注射器，n=110）的平均浓度-时间曲线相似。几何最小二乘均值的逆变换比值（自动注射器/预充注射器）的点估计值，最大血浆浓度、从 0 时间到最后可测量药物浓度的血浆浓度-时间曲线下面积、从 0 时间外推至无穷大的血浆浓度-时间曲线下面积分别为 1.03、1.04 和 1.05，90%置信区间完全包含在 0.8 至 1.25 的生物等效性范围内。对于这两组，中位达到最大观测浓度的时间为 5 天，平均终末消除半衰期约为 29 天。在自动注射器组，39 名（36%）受试者和预充注射器组 26 名（24%）受试者报告了与治疗相关的不良事件，大多数为非严重的注射部位反应。治疗后出现抗药物抗体反应的发生率低，在自动注射器组（n=3；3%）和预充注射器组（n=4；4%）之间分布均匀。这些结果表明，依洛尤单抗自动注射器制剂提供了一种易于使用的 PK 特征，与预充注射器具有相似的安全性和耐受性特征。
