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

I. Takács, E. Jókai, D. E. Kováts, I. Aradi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Summary: 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. Introduction: 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. Methods: 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 (AUC0-tlast) and peak exposure (Cmax), 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. Results: 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 AUC0-tlast and Cmax, 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 Cmax, respectively. Analysis of the safety data did not reveal any differences between RGB-10 and its reference. Conclusion: 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.

Original languageEnglish
JournalOsteoporosis International
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Biosimilar Pharmaceuticals
Teriparatide
Osteoporosis
Pharmacokinetics
Marketing
Safety
Osteology
Calcium
Anabolic Agents
Therapeutic Equivalency
Cross-Over Studies
Area Under Curve
Therapeutics
Enzyme-Linked Immunosorbent Assay
Bone and Bones
Serum

Keywords

  • Bioequivalence
  • Biosimilar
  • Clinical trial
  • Osteoporosis
  • Teriparatide

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

The first biosimilar approved for the treatment of osteoporosis : results of a comparative pharmacokinetic/pharmacodynamic study. / Takács, I.; Jókai, E.; Kováts, D. E.; Aradi, I.

In: Osteoporosis International, 01.01.2018.

Research output: Contribution to journalArticle

@article{26ce0959c40941458232cabfd0b2e97b,
title = "The first biosimilar approved for the treatment of osteoporosis: results of a comparative pharmacokinetic/pharmacodynamic study",
abstract = "Summary: 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{\circledR}) was granted by the European Medicines Agency in 2017. Introduction: 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. Methods: Subsequent to establishing comparability on the quality and non-clinical levels between RGB-10, a biosimilar teriparatide, and its reference product (Forsteo{\circledR}), 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 (AUC0-tlast) and peak exposure (Cmax), 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. Results: 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 AUC0-tlast and Cmax, 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 Cmax, respectively. Analysis of the safety data did not reveal any differences between RGB-10 and its reference. Conclusion: Based on the high level of similarity in the preclinical data and the results of this clinical study, marketing authorisation for RGB-10 (Terrosa{\circledR}) was granted by the European Medicines Agency (EMA) in 2017.",
keywords = "Bioequivalence, Biosimilar, Clinical trial, Osteoporosis, Teriparatide",
author = "I. Tak{\'a}cs and E. J{\'o}kai and Kov{\'a}ts, {D. E.} and I. Aradi",
year = "2018",
month = "1",
day = "1",
doi = "10.1007/s00198-018-4741-0",
language = "English",
journal = "Osteoporosis International",
issn = "0937-941X",
publisher = "Springer London",

}

TY - JOUR

T1 - The first biosimilar approved for the treatment of osteoporosis

T2 - results of a comparative pharmacokinetic/pharmacodynamic study

AU - Takács, I.

AU - Jókai, E.

AU - Kováts, D. E.

AU - Aradi, I.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Summary: 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. Introduction: 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. Methods: 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 (AUC0-tlast) and peak exposure (Cmax), 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. Results: 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 AUC0-tlast and Cmax, 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 Cmax, respectively. Analysis of the safety data did not reveal any differences between RGB-10 and its reference. Conclusion: 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.

AB - Summary: 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. Introduction: 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. Methods: 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 (AUC0-tlast) and peak exposure (Cmax), 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. Results: 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 AUC0-tlast and Cmax, 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 Cmax, respectively. Analysis of the safety data did not reveal any differences between RGB-10 and its reference. Conclusion: 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.

KW - Bioequivalence

KW - Biosimilar

KW - Clinical trial

KW - Osteoporosis

KW - Teriparatide

UR - http://www.scopus.com/inward/record.url?scp=85055710879&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85055710879&partnerID=8YFLogxK

U2 - 10.1007/s00198-018-4741-0

DO - 10.1007/s00198-018-4741-0

M3 - Article

AN - SCOPUS:85055710879

JO - Osteoporosis International

JF - Osteoporosis International

SN - 0937-941X

ER -