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Pharmacokinetics, Pharmacodynamics, Safety and Immunogenicity of CMAB807, a New Denosumab Biosimilar, in Healthy Chinese Subjects

Objective: Pharmacokinetics (PK), pharmacodynamics (PD), safety and immunogenicity studies were conducted to evaluate the bioequivalence of CMAB807, a biosimilar to denosumab (Prolia(®)), which is the only approved RANKL inhibitor for the treatment of osteoporosis. Methods: In this randomized, doubl...

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Autores principales: Chen, Hanjing, Chen, Weili, Yuan, Fei, Guo, Qingcheng, Zhang, Xunmin, Wang, Chenguang, Li, Xuening
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8819684/
https://www.ncbi.nlm.nih.gov/pubmed/35140619
http://dx.doi.org/10.3389/fphar.2022.821944
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author Chen, Hanjing
Chen, Weili
Yuan, Fei
Guo, Qingcheng
Zhang, Xunmin
Wang, Chenguang
Li, Xuening
author_facet Chen, Hanjing
Chen, Weili
Yuan, Fei
Guo, Qingcheng
Zhang, Xunmin
Wang, Chenguang
Li, Xuening
author_sort Chen, Hanjing
collection PubMed
description Objective: Pharmacokinetics (PK), pharmacodynamics (PD), safety and immunogenicity studies were conducted to evaluate the bioequivalence of CMAB807, a biosimilar to denosumab (Prolia(®)), which is the only approved RANKL inhibitor for the treatment of osteoporosis. Methods: In this randomized, double-blind, single-dose phase I study, 132 healthy Chinese male subjects received a subcutaneous injection of 60 mg of CMAB807 or denosumab at a 1:1 ratio. The PK, PD, safety and immunogenicity results were assessed prior to and up to 126 days after administration. Results: The PK profiles of CMAB807 and denosumab were similar. The geometric mean ratios of the maximum concentration (C(max)), AUC(0-t) and AUC(o-∞) were 102.41, 104.15 and 103.89%, respectively, and the 90% confidence interval was observed to be within 80.00–125.00%, which indicated the bioequivalence of CMAB807 and denosumab. The PD profiles of the two groups were also comparable. The production of the C-terminal cross-linking telopeptide of type I collagen (CTX1) was inhibited by up to 85% for 10 days, and this inhibition was sustained for up to 126 days in both the CMAB807 and denosumab groups. No subjects in the CMAB807 group, three subjects in the denosumab group before administration, and two subjects in the denosumab group after administration were positive for anti-drug antibody (ADA). Adverse events (AEs) were observed in 98.5% of subjects in both groups. The most common AE recorded was increased parathyroid hormone (PTH) levels, with incidences of 92.4 and 95.5% in the CMAB807 and denosumab groups, respectively. No clinically meaningful differences were observed in safety and immunogenicity between CMAB807 and denosumab. Conclusion: CMAB807 represents a new potential treatment option for patients with osteoporosis. Clinical Trial Registration: https://clinicaltrials.gov (Registration No. NCT03925051), http://www.chinadrugtrial/org.cn/index.html (Registration No. CTR20190800).
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spelling pubmed-88196842022-02-08 Pharmacokinetics, Pharmacodynamics, Safety and Immunogenicity of CMAB807, a New Denosumab Biosimilar, in Healthy Chinese Subjects Chen, Hanjing Chen, Weili Yuan, Fei Guo, Qingcheng Zhang, Xunmin Wang, Chenguang Li, Xuening Front Pharmacol Pharmacology Objective: Pharmacokinetics (PK), pharmacodynamics (PD), safety and immunogenicity studies were conducted to evaluate the bioequivalence of CMAB807, a biosimilar to denosumab (Prolia(®)), which is the only approved RANKL inhibitor for the treatment of osteoporosis. Methods: In this randomized, double-blind, single-dose phase I study, 132 healthy Chinese male subjects received a subcutaneous injection of 60 mg of CMAB807 or denosumab at a 1:1 ratio. The PK, PD, safety and immunogenicity results were assessed prior to and up to 126 days after administration. Results: The PK profiles of CMAB807 and denosumab were similar. The geometric mean ratios of the maximum concentration (C(max)), AUC(0-t) and AUC(o-∞) were 102.41, 104.15 and 103.89%, respectively, and the 90% confidence interval was observed to be within 80.00–125.00%, which indicated the bioequivalence of CMAB807 and denosumab. The PD profiles of the two groups were also comparable. The production of the C-terminal cross-linking telopeptide of type I collagen (CTX1) was inhibited by up to 85% for 10 days, and this inhibition was sustained for up to 126 days in both the CMAB807 and denosumab groups. No subjects in the CMAB807 group, three subjects in the denosumab group before administration, and two subjects in the denosumab group after administration were positive for anti-drug antibody (ADA). Adverse events (AEs) were observed in 98.5% of subjects in both groups. The most common AE recorded was increased parathyroid hormone (PTH) levels, with incidences of 92.4 and 95.5% in the CMAB807 and denosumab groups, respectively. No clinically meaningful differences were observed in safety and immunogenicity between CMAB807 and denosumab. Conclusion: CMAB807 represents a new potential treatment option for patients with osteoporosis. Clinical Trial Registration: https://clinicaltrials.gov (Registration No. NCT03925051), http://www.chinadrugtrial/org.cn/index.html (Registration No. CTR20190800). Frontiers Media S.A. 2022-01-24 /pmc/articles/PMC8819684/ /pubmed/35140619 http://dx.doi.org/10.3389/fphar.2022.821944 Text en Copyright © 2022 Chen, Chen, Yuan, Guo, Zhang, Wang and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Chen, Hanjing
Chen, Weili
Yuan, Fei
Guo, Qingcheng
Zhang, Xunmin
Wang, Chenguang
Li, Xuening
Pharmacokinetics, Pharmacodynamics, Safety and Immunogenicity of CMAB807, a New Denosumab Biosimilar, in Healthy Chinese Subjects
title Pharmacokinetics, Pharmacodynamics, Safety and Immunogenicity of CMAB807, a New Denosumab Biosimilar, in Healthy Chinese Subjects
title_full Pharmacokinetics, Pharmacodynamics, Safety and Immunogenicity of CMAB807, a New Denosumab Biosimilar, in Healthy Chinese Subjects
title_fullStr Pharmacokinetics, Pharmacodynamics, Safety and Immunogenicity of CMAB807, a New Denosumab Biosimilar, in Healthy Chinese Subjects
title_full_unstemmed Pharmacokinetics, Pharmacodynamics, Safety and Immunogenicity of CMAB807, a New Denosumab Biosimilar, in Healthy Chinese Subjects
title_short Pharmacokinetics, Pharmacodynamics, Safety and Immunogenicity of CMAB807, a New Denosumab Biosimilar, in Healthy Chinese Subjects
title_sort pharmacokinetics, pharmacodynamics, safety and immunogenicity of cmab807, a new denosumab biosimilar, in healthy chinese subjects
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8819684/
https://www.ncbi.nlm.nih.gov/pubmed/35140619
http://dx.doi.org/10.3389/fphar.2022.821944
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