Equivalence trial of proposed denosumab biosimilar GP2411 and
reference denosumab in postmenopausal osteoporosis: the ROSALIA
study

J 2024

Equivalence trial of proposed denosumab biosimilar GP2411 and reference denosumab in postmenopausal osteoporosis: the ROSALIA study

JEKA, Slawomir, Eva DOKOUPILOVÁ, Alan KIVITZ, Pawel ZUCHOWSKI, Barbara VOGG et. al.

Basic information

Original name

Equivalence trial of proposed denosumab biosimilar GP2411 and reference denosumab in postmenopausal osteoporosis: the ROSALIA study

Authors

JEKA, Slawomir (616 Poland), Eva DOKOUPILOVÁ (203 Czech Republic, belonging to the institution), Alan KIVITZ (840 United States of America), Pawel ZUCHOWSKI (616 Poland), Barbara VOGG (276 Germany), Natalia KRIVTSOVA (276 Germany), Susmit SEKHAR (276 Germany), Samik BANERJEE (276 Germany), Arnd SCHWEBIG (276 Germany), Johann POETZL (276 Germany), Jean-Jacques BODY (56 Belgium) and Richard EASTELL (826 United Kingdom of Great Britain and Northern Ireland)

Edition

Journal of bone and mineral research, Hoboken, Wiley, 2024, 0884-0431

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30202 Endocrinology and metabolism

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 6.200 in 2022

Organization unit

Faculty of Pharmacy

DOI

http://dx.doi.org/10.1093/jbmr/zjae016

UT WoS

001205748100001

Keywords in English

diseases and disorders of/related to bone: osteoporosis; clinical trials; bone modeling and remodeling: biochemical markers of bone turnover

Abstract

V originále

Denosumab is a monoclonal antibody used to reduce risk of fractures in osteoporosis. ROSALIA was a multicenter, double-blind, randomized, integrated phase I/phase III study comparing the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and safety of proposed biosimilar denosumab GP2411 with reference denosumab (REF-DMAb) (Prolia (R); Amgen). Postmenopausal women with osteoporosis were randomized 1:1 to 2 60-mg doses of GP2411 or REF-DMAb, one at study start and one at week 26. At week 52, the REF-DMAb group was re-randomized 1:1 to a third dose of REF-DMAb or switch to GP2411. The primary efficacy endpoint was percentage change from baseline (%CfB) in LS-BMD at week 52. Secondary efficacy endpoints were %CfB in LS-BMD, FN-BMD, and TH-BMD at weeks 26 and 78 (and week 52 for FN-BMD and TH-BMD). Primary PK and PD endpoints were the area under the serum concentration-time curve extrapolated to infinity and maximum drug serum concentration at week 26, and the area under the effect-time curve of the %CfB in serum CTX at week 26. Secondary PK and PD endpoints included drug serum concentrations and %CfB in serum CTX and P1NP during the study period. Similar efficacy was demonstrated at week 52, with 95% CIs of the difference in %CfB in LS-BMD between treatment groups fully contained within prespecified equivalence margins. Similarity in PK and PD was demonstrated at week 26. Immunogenicity was similar between groups and was not impacted by treatment switch. The rate of new vertebral fractures was comparable. Treatment-emergent adverse events were comparable between groups (63.6% [GP2411/GP2411]; 76.0% [REF-DMAb/REF-DMAb]; 76.6% [REF-DMAb/GP2411]). In conclusion, ROSALIA showed similar efficacy, PK and PD, and comparable safety and immunogenicity of GP2411 to REF-DMAb in postmenopausal osteoporosis.

Citovat

JEKA, Slawomir, Eva DOKOUPILOVÁ, Alan KIVITZ, Pawel ZUCHOWSKI, Barbara VOGG, Natalia KRIVTSOVA, Susmit SEKHAR, Samik BANERJEE, Arnd SCHWEBIG, Johann POETZL, Jean-Jacques BODY and Richard EASTELL. Equivalence trial of proposed denosumab biosimilar GP2411 and reference denosumab in postmenopausal osteoporosis: the ROSALIA study. Journal of bone and mineral research. Hoboken: Wiley, 2024, vol. 39, No 3, p. 202-210. ISSN 0884-0431. Available from: https://dx.doi.org/10.1093/jbmr/zjae016.

@article{2428280,
   author = {Jeka, Slawomir and Dokoupilová, Eva and Kivitz, Alan and Zuchowski, Pawel and Vogg, Barbara and Krivtsova, Natalia and Sekhar, Susmit and Banerjee, Samik and Schwebig, Arnd and Poetzl, Johann and Body, JeanandJacques and Eastell, Richard},
   article_location = {Hoboken},
   article_number = {3},
   doi = {http://dx.doi.org/10.1093/jbmr/zjae016},
   keywords = {diseases and disorders of/related to bone: osteoporosis; clinical trials; bone modeling and remodeling: biochemical markers of bone turnover},
   language = {eng},
   issn = {0884-0431},
   journal = {Journal of bone and mineral research},
   title = {Equivalence trial of proposed denosumab biosimilar GP2411 and reference denosumab in postmenopausal osteoporosis: the ROSALIA study},
   url = {https://watermark.silverchair.com/zjae016.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAA2YwggNiBgkqhkiG9w0BBwagggNTMIIDTwIBADCCA0gGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMXnLf_ibAi5W763kFAgEQgIIDGTLW7HAwZxncFjr5930K4JP9kA_ZoHMZtCtl9TFxfRG_1D},
   volume = {39},
   year = {2024}
}

TY  - JOUR
ID  - 2428280
AU  - Jeka, Slawomir - Dokoupilová, Eva - Kivitz, Alan - Zuchowski, Pawel - Vogg, Barbara - Krivtsova, Natalia - Sekhar, Susmit - Banerjee, Samik - Schwebig, Arnd - Poetzl, Johann - Body, Jean-Jacques - Eastell, Richard
PY  - 2024
TI  - Equivalence trial of proposed denosumab biosimilar GP2411 and reference denosumab in postmenopausal osteoporosis: the ROSALIA study
JF  - Journal of bone and mineral research
VL  - 39
IS  - 3
SP  - 202-210
EP  - 202-210
PB  - Wiley
SN  - 08840431
KW  - diseases and disorders of/related to bone: osteoporosis
KW  - clinical trials
KW  - bone modeling and remodeling: biochemical markers of bone turnover
UR  - https://watermark.silverchair.com/zjae016.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAA2YwggNiBgkqhkiG9w0BBwagggNTMIIDTwIBADCCA0gGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMXnLf_ibAi5W763kFAgEQgIIDGTLW7HAwZxncFjr5930K4JP9kA_ZoHMZtCtl9TFxfRG_1D
N2  - Denosumab is a monoclonal antibody used to reduce risk of fractures in osteoporosis. ROSALIA was a multicenter, double-blind, randomized, integrated phase I/phase III study comparing the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and safety of proposed biosimilar denosumab GP2411 with reference denosumab (REF-DMAb) (Prolia (R); Amgen). Postmenopausal women with osteoporosis were randomized 1:1 to 2 60-mg doses of GP2411 or REF-DMAb, one at study start and one at week 26. At week 52, the REF-DMAb group was re-randomized 1:1 to a third dose of REF-DMAb or switch to GP2411. The primary efficacy endpoint was percentage change from baseline (%CfB) in LS-BMD at week 52. Secondary efficacy endpoints were %CfB in LS-BMD, FN-BMD, and TH-BMD at weeks 26 and 78 (and week 52 for FN-BMD and TH-BMD). Primary PK and PD endpoints were the area under the serum concentration-time curve extrapolated to infinity and maximum drug serum concentration at week 26, and the area under the effect-time curve of the %CfB in serum CTX at week 26. Secondary PK and PD endpoints included drug serum concentrations and %CfB in serum CTX and P1NP during the study period. Similar efficacy was demonstrated at week 52, with 95% CIs of the difference in %CfB in LS-BMD between treatment groups fully contained within prespecified equivalence margins. Similarity in PK and PD was demonstrated at week 26. Immunogenicity was similar between groups and was not impacted by treatment switch. The rate of new vertebral fractures was comparable. Treatment-emergent adverse events were comparable between groups (63.6% [GP2411/GP2411]; 76.0% [REF-DMAb/REF-DMAb]; 76.6% [REF-DMAb/GP2411]). In conclusion, ROSALIA showed similar efficacy, PK and PD, and comparable safety and immunogenicity of GP2411 to REF-DMAb in postmenopausal osteoporosis.
ER  -

JEKA, Slawomir, Eva DOKOUPILOVÁ, Alan KIVITZ, Pawel ZUCHOWSKI, Barbara VOGG, Natalia KRIVTSOVA, Susmit SEKHAR, Samik BANERJEE, Arnd SCHWEBIG, Johann POETZL, Jean-Jacques BODY and Richard EASTELL. Equivalence trial of proposed denosumab biosimilar GP2411 and reference denosumab in postmenopausal osteoporosis: the ROSALIA study. \textit{Journal of bone and mineral research}. Hoboken: Wiley, 2024, vol.~39, No~3, p.~202-210. ISSN~0884-0431. Available from: https://dx.doi.org/10.1093/jbmr/zjae016.

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