Semmelweis University, Budapest, Hungary.
Gedeon Richter Plc, 19-21 Gyömrői út, Budapest, H-1103, Hungary.
Osteoporos Int. 2019 Mar;30(3):675-683. doi: 10.1007/s00198-018-4741-0. Epub 2018 Oct 24.
To demonstrate the clinical comparability between RGB-10 (a biosimilar teriparatide) and the originator, a comparative pharmacokinetic trial was conducted. The study was successful in establishing bioequivalence. Marketing authorisation for RGB-10 (Terrosa®) was granted by the European Medicines Agency in 2017.
Teriparatide, the first bone anabolic agent, is the biologically active fragment of human parathyroid hormone. The imminent patent expiry of the originator will open the door for biosimilars to enter the osteology market, thereby improving access to a highly effective, yet prohibitively expensive therapy.
Subsequent to establishing comparability on the quality and non-clinical levels between RGB-10, a biosimilar teriparatide, and its reference product (Forsteo®), a randomised, double-blind, 2-way cross-over comparative study (duration: four days) was conducted in 54 healthy women (ages: 18 to 55 years) to demonstrate the pharmacokinetic/pharmacodynamic (PK/PD) equivalence and comparable safety of these products. Extents of exposure (AUC) and peak exposure (C), as measured by means of ELISA, were evaluated as co-primary PK endpoints, and serum calcium levels, as measured using standard automated techniques, were assessed for PD effects. Safety was monitored throughout the study.
The 94.12% CIs for the ratio of the test to the reference treatments, used due to the two-stage design (85.20-98.60% and 85.51-99.52% for AUC and C, respectively), fell within the 80.00-125.00% acceptance range. The calcium PD parameters were essentially identical with geometric mean ratios (GMRs) of 99.93% and 99.87% for AUC and C, respectively. Analysis of the safety data did not reveal any differences between RGB-10 and its reference.
Based on the high level of similarity in the preclinical data and the results of this clinical study, marketing authorisation for RGB-10 (Terrosa®) was granted by the European Medicines Agency (EMA) in 2017.
展示 RGB-10（一种人生长激素类似物）与原研药之间的临床可比性，开展了一项比较药代动力学试验。研究成功证实了生物等效性。2017 年，欧洲药品管理局批准 RGB-10（特罗萨®）上市。
特立帕肽是首个骨合成代谢药物，是人类甲状旁腺激素的生物活性片段。原研药的专利即将到期，这将为生物类似药进入骨科学领域打开大门，从而改善对这种高效但价格昂贵的治疗方法的可及性。
在确定 RGB-10（一种人生长激素类似物）与其参比产品（福善美®）在质量和非临床水平上具有可比性之后，开展了一项随机、双盲、两周期交叉比较研究（持续时间：4 天），纳入 54 例健康女性（年龄：18 至 55 岁），以证明这些产品的药代动力学/药效学（PK/PD）等效性和安全性相当。采用 ELISA 法测定的暴露程度（AUC）和峰暴露（C）作为主要 PK 终点，采用标准自动化技术测定血清钙水平，以评估 PD 效应。在整个研究过程中监测安全性。
由于采用两阶段设计（AUC 和 C 的比值分别为 85.20-98.60%和 85.51-99.52%），测试治疗与参比治疗的比值的 94.12%置信区间（CI）落在 80.00-125.00%接受范围内。钙 PD 参数基本相同，AUC 和 C 的几何均数比值（GMR）分别为 99.93%和 99.87%。安全性数据分析未显示 RGB-10 与参比药物之间存在差异。
基于高度相似的临床前数据和这项临床研究结果，2017 年欧洲药品管理局（EMA）批准 RGB-10（特罗萨®）上市。
