Efficacy and safety of the biosimilar denosumab candidate (Arylia) compared to the reference product (Prolia®) in postmenopausal osteoporosis: a phase III, randomized, two-armed, double-blind, parallel, active-controlled, and noninferiority clinical trial.
Arylia
Biosimilar
Denosumab
Osteoporosis
Prolia®
Journal
Arthritis research & therapy
ISSN: 1478-6362
Titre abrégé: Arthritis Res Ther
Pays: England
ID NLM: 101154438
Informations de publication
Date de publication:
30 06 2022
30 06 2022
Historique:
received:
11
04
2022
accepted:
15
06
2022
entrez:
30
6
2022
pubmed:
1
7
2022
medline:
6
7
2022
Statut:
epublish
Résumé
Osteoporosis is a global health concern with an increasing prevalence worldwide. Denosumab is an antiresoptive agent that has been demonstrated to be effective and safe in osteoporotic patients. This study aimed to compare the efficacy and safety of the biosimilar denosumab candidate (Arylia) to the originator product (Prolia®) in postmenopausal osteoporotic patients. In this randomized, double-blind, active-controlled, noninferiority trial, postmenopausal osteoporotic patients received 60 mg of subcutaneous Arylia or Prolia® at months 0, 6, and 12 and were followed up for 18 months. The primary endpoint was the noninferiority of the biosimilar product to the reference product in the percentage change of bone mineral density (BMD) in 18 months at the lumbar spine (L A total of 190 patients were randomized to receive either biosimilar (n = 95) or reference (n = 95) denosumab. In the per-protocol (PP) analysis, the lower limits of the 95% two-sided confidence intervals of the difference between Arylia and Prolia® in increasing BMD were greater than the predetermined noninferiority margin of - 1.78 at the lumbar spine, total hip, and femoral neck sites (mean differences [95% CIs] of 0.39 [- 1.34 to 2.11], 0.04 [- 1.61 to 1.69], and 0.41 [- 1.58 to 2.40], respectively). The two products were also comparable in terms of safety, new vertebral fractures, and trend of BTMs. The efficacy of the biosimilar denosumab was shown to be noninferior to that of the reference denosumab, with a comparable safety profile at 18 months. ClinicalTrials.gov, NCT03293108 ; Registration date: 2017-09-19.
Sections du résumé
BACKGROUND/OBJECTIVE
Osteoporosis is a global health concern with an increasing prevalence worldwide. Denosumab is an antiresoptive agent that has been demonstrated to be effective and safe in osteoporotic patients. This study aimed to compare the efficacy and safety of the biosimilar denosumab candidate (Arylia) to the originator product (Prolia®) in postmenopausal osteoporotic patients.
METHODS
In this randomized, double-blind, active-controlled, noninferiority trial, postmenopausal osteoporotic patients received 60 mg of subcutaneous Arylia or Prolia® at months 0, 6, and 12 and were followed up for 18 months. The primary endpoint was the noninferiority of the biosimilar product to the reference product in the percentage change of bone mineral density (BMD) in 18 months at the lumbar spine (L
RESULTS
A total of 190 patients were randomized to receive either biosimilar (n = 95) or reference (n = 95) denosumab. In the per-protocol (PP) analysis, the lower limits of the 95% two-sided confidence intervals of the difference between Arylia and Prolia® in increasing BMD were greater than the predetermined noninferiority margin of - 1.78 at the lumbar spine, total hip, and femoral neck sites (mean differences [95% CIs] of 0.39 [- 1.34 to 2.11], 0.04 [- 1.61 to 1.69], and 0.41 [- 1.58 to 2.40], respectively). The two products were also comparable in terms of safety, new vertebral fractures, and trend of BTMs.
CONCLUSION
The efficacy of the biosimilar denosumab was shown to be noninferior to that of the reference denosumab, with a comparable safety profile at 18 months.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT03293108 ; Registration date: 2017-09-19.
Identifiants
pubmed: 35773713
doi: 10.1186/s13075-022-02840-8
pii: 10.1186/s13075-022-02840-8
pmc: PMC9245232
doi:
Substances chimiques
Biosimilar Pharmaceuticals
0
Bone Density Conservation Agents
0
Denosumab
4EQZ6YO2HI
Banques de données
ClinicalTrials.gov
['NCT03293108']
Types de publication
Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
161Informations de copyright
© 2022. The Author(s).
Références
Endocr Pract. 2020 May;26(Suppl 1):1-46
pubmed: 32427503
Indian J Pharmacol. 2021 Jan-Feb;53(1):6-12
pubmed: 33975993
Ther Adv Musculoskelet Dis. 2011 Dec;3(6):271-82
pubmed: 22870485
Arch Osteoporos. 2021 Jan 21;16(1):16
pubmed: 33475880
Br J Pharmacol. 2021 May;178(9):1891-1906
pubmed: 32060897
Eur J Rheumatol. 2017 Mar;4(1):46-56
pubmed: 28293453
Ther Clin Risk Manag. 2012;8:295-306
pubmed: 22767993
J Orthop Traumatol. 2017 Nov;18(Suppl 1):3-36
pubmed: 29058226
J Clin Endocrinol Metab. 2019 May 1;104(5):1623-1630
pubmed: 30907957
Ann Endocrinol (Paris). 2015 Dec;76(6):650-7
pubmed: 26639186
J Womens Health (Larchmt). 2011 Apr;20(4):525-31
pubmed: 21438699
Int J Womens Health. 2015 Oct 13;7:833-9
pubmed: 26508890
J Orthop Surg Res. 2021 Aug 27;16(1):533
pubmed: 34452621
Drug Des Devel Ther. 2020 Oct 01;14:4029-4051
pubmed: 33061307
Osteoporos Int. 2014 Oct;25(10):2359-81
pubmed: 25182228
Bone Rep. 2020 Jul 04;13:100293
pubmed: 32676524
J Clin Endocrinol Metab. 2008 Jun;93(6):2149-57
pubmed: 18381571
Lancet Oncol. 2018 Mar;19(3):370-381
pubmed: 29429912
N Engl J Med. 2009 Aug 20;361(8):756-65
pubmed: 19671655
Neurosurg Focus. 2021 Jun;50(6):E13
pubmed: 34062504
J Osteoporos. 2016;2016:8738959
pubmed: 27579211
Sci Rep. 2021 Jun 3;11(1):11801
pubmed: 34083636
Lancet Diabetes Endocrinol. 2018 Jun;6(6):445-454
pubmed: 29631782