Comparative Physicochemical and Biological Characterisation of the Similar Biological Medicinal Product Teriparatide and Its Reference Medicinal Product

3区 · 医学

Article

作者: Nebel, Merle ; Schäfer, Tamás ; Háda, Viktor ; Hevér, Helga ; Klingelhöfer, Sonja ; Kovács, Piroska ; Kiss, Róbert ; Stadie, Tanja ; Urbányi, Zoltán

BACKGROUNDIn January 2017, the European Commission approved Terrosa^® (company code RGB-10) as one of the first biosimilar medicinal products of teriparatide for the same indications as for the reference medicinal product Forsteo^® (Lilly France S.A.S.), which has been on the market in the European Union since 2003. The active pharmaceutical ingredient of the reference medicinal product is the biologically active 1-34 fragment of the endogenous human parathyroid hormone [PTH(1-34)]. It is one of the three bone anabolic agents used in the treatment of osteoporosis promoting bone formation and preventing fragility fractures.OBJECTIVEThe objective of this paper is to summarise the results of the comparative analysis of representative batches of both the RGB-10 drug product and the reference medicinal product performed by physicochemical and in vitro biological methods.METHODSA series of state-of-the-art analytical methods were applied in a comparative head-to-head manner for testing the similarity in respect to purity, content, structure and potency.RESULTSBased on the results of the comprehensive physicochemical and biological characterisation, RGB-10 proved to be highly similar to the reference medicinal product with respect to the critical quality attributes investigated.CONCLUSIONThe results of the quality comparability study demonstrated similarity of RGB-10 to the reference medicinal product, providing the scientific basis for conducting a specifically designed clinical programme, and supported registration of the Marketing Authorisation Application of RGB-10 in the EU.

2019-10-01·Osteoporosis International2区 · 医学

A multicenter, randomized, rater-blinded, parallel-group, phase 3 study to compare the efficacy, safety, and immunogenicity of biosimilar RGB-10 and reference once-daily teriparatide in patients with osteoporosis

2区 · 医学

Article

作者: Narita, R ; Watanabe, M ; Tomomitsu, M ; Yokoyama, Y ; Hagino, H

The efficacy and safety of RGB-10 and reference teriparatide were evaluated in a randomized 52-week study in 250 patients with osteoporosis at high risk of fracture. RGB-10 was equivalent to reference teriparatide in efficacy and had a comparable safety profile.INTRODUCTIONRGB-10 is the first biosimilar teriparatide authorized in the European Union. This multicenter, randomized, rater-blinded, parallel-group phase 3 study evaluated equivalence in efficacy and compared safety between RGB-10 and reference teriparatide in patients with osteoporosis at high risk of fracture for registration in Japan.METHODSAmbulatory postmenopausal women and men (≥ 55 years of age) with osteoporosis at high risk of fracture were randomized 1:1 to receive either RGB-10 or reference teriparatide 20 μg once daily via subcutaneous self-injection for 52 weeks. The primary efficacy endpoint was the percent change from baseline to 52 weeks in lumbar spine (L2-L4) bone mineral density (BMD). Safety outcomes and immunogenicity were also assessed.RESULTSIn total, 250 patients (125 in each group) were randomized. The percent change from baseline to 52 weeks in lumbar spine (L2-L4) BMD (mean ± standard deviation) was 8.94% ± 6.19% in the RGB-10 group and 9.65% ± 6.22% in the reference teriparatide group. The estimated between-group difference (95% confidence interval) was - 0.65% (- 2.17% to - 0.87%) within the pre-specified equivalence margin (± 2.8%), which indicates equivalence in efficacy between the two groups. Changes in BMD at lumbar spine (L1-L4), femoral neck, and total hip and serum procollagen type I amino-terminal propeptide were also similar between the groups. Safety profiles, including immunogenicity, were comparable.CONCLUSIONSThe therapeutic equivalence of RGB-10 to reference teriparatide was demonstrated. RGB-10 had comparable safety profile to that of reference teriparatide.

2019-03-01·Osteoporosis International2区 · 医学

The first biosimilar approved for the treatment of osteoporosis: results of a comparative pharmacokinetic/pharmacodynamic study

2区 · 医学

Article

作者: Kováts, D E ; Takács, I ; Jókai, E ; Aradi, I

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.INTRODUCTIONTeriparatide, 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.METHODSSubsequent 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_0-tlast) and peak exposure (C_max), 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.RESULTSThe 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_0-tlast and C_max, 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_max, respectively. Analysis of the safety data did not reveal any differences between RGB-10 and its reference.CONCLUSIONBased 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.

100 项与特立帕肽生物类似药(The Chemical Works of Gedeon Richter Plc) 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D06078	特立帕肽生物类似药(The Chemical Works of Gedeon Richter Plc)	H05AA02	-

研发状态

10 条最早获批的记录,

后查看更多信息

适应症	国家/地区	公司	日期
原发性骨质疏松症	澳大利亚	Gedeon Richter Australia Pty Ltd.	2020-12-01
骨质疏松症	日本	Mochida Pharmaceutical Co., Ltd.	2019-09-20
糖皮质激素诱导的骨质疏松症	列支敦士登	Chemical Works of Gedeon Richter Plc	2017-01-04
糖皮质激素诱导的骨质疏松症	冰岛	Chemical Works of Gedeon Richter Plc	2017-01-04
糖皮质激素诱导的骨质疏松症	挪威	Chemical Works of Gedeon Richter Plc	2017-01-04
糖皮质激素诱导的骨质疏松症	欧盟	Chemical Works of Gedeon Richter Plc	2017-01-04
绝经期后骨质疏松	列支敦士登	Chemical Works of Gedeon Richter Plc	2017-01-04
绝经期后骨质疏松	欧盟	Chemical Works of Gedeon Richter Plc	2017-01-04
绝经期后骨质疏松	冰岛	Chemical Works of Gedeon Richter Plc	2017-01-04
绝经期后骨质疏松	挪威	Chemical Works of Gedeon Richter Plc	2017-01-04
骨质疏松性骨折	冰岛	Chemical Works of Gedeon Richter Plc	2017-01-04
骨质疏松性骨折	欧盟	Chemical Works of Gedeon Richter Plc	2017-01-04
骨质疏松性骨折	挪威	Chemical Works of Gedeon Richter Plc	2017-01-04
骨质疏松性骨折	列支敦士登	Chemical Works of Gedeon Richter Plc	2017-01-04