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

Ahmadreza Jamshidi, Mahdi Vojdanian, Mohsen Soroush, Mahmoud Akbarian, Mehrdad Aghaei, Asghar Hajiabbasi, Zahra Mirfeizi, Alireza Khabbazi, Gholamhosein Alishiri, Anousheh Haghighi, Ahmad Salimzadeh, Hadi Karimzadeh, Fatemeh Shirani, Mohammad Reza Hatef Fard, MohammadAli Nazarinia, Soosan Soroosh, Nassim Anjidani, Farhad Gharibdoost, Ahmadreza Jamshidi, Mahdi Vojdanian, Mohsen Soroush, Mahmoud Akbarian, Mehrdad Aghaei, Asghar Hajiabbasi, Zahra Mirfeizi, Alireza Khabbazi, Gholamhosein Alishiri, Anousheh Haghighi, Ahmad Salimzadeh, Hadi Karimzadeh, Fatemeh Shirani, Mohammad Reza Hatef Fard, MohammadAli Nazarinia, Soosan Soroosh, Nassim Anjidani, Farhad Gharibdoost

Abstract

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 (L1-L4), total hip, and femoral neck. The secondary endpoints were safety assessment, the incidence of new vertebral fractures, and the trend of bone turnover markers (BTMs).

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.

Keywords: Arylia; Biosimilar; Denosumab; Osteoporosis; Prolia®.

Conflict of interest statement

Nassim Anjidani is the head of the medical department of Orchid Pharmed Company, which is in collaboration with AryoGen Pharmed Company with respect to conducting clinical trials. There are no other potential conflicts of interest pertaining to this article.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Patient flow diagram
Fig. 2
Fig. 2
Mean percentage change in BMD of the lumbar spine (L1–L4) (a), total hip (b), and femoral neck (c). Error bars show standard error. The plot is based on the PP set
Fig. 3
Fig. 3
Forest plot for comparing Arylia versus Prolia® in terms of mean percent changes in BMD of the lumbar spine (L1–L4), total hip, and femoral neck at 18 months of the study. Forest plot demonstrating both t test analysis and ANCOVA model for PP set
Fig. 4
Fig. 4
Medians and IQRs for biochemical markers of bone metabolism at 18 months of the trial

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