Biosimilar denosumab not inferior to the reference product in postmenopausal women


The study of postmenopausal women in Iran found that the efficacy of the biosimilar was not inferior to the reference product and the safety was comparable after 18 months.

As the world’s population continues to age, the incidence of osteoporosis is expected to continue to rise, making it important to find ways to manage the disease and develop additional treatments.

Compared to the reference product, the efficacy of a biosimilar candidate denosumab (Arylia developed by AryoGen Pharmed in Iran) is not inferior and the tolerance is comparable after 18 months, according to a study Posted in Arthritis research and therapy. Currently, there are no biosimilars approved by the FDA to treat osteoporosis, although the European Medicines Agency granted marketing authorization for a teriparatide biosimilar in 2017. In the United States, the patents for denosumab (marketed as Prolia and Xgeva depending on the indication) expire in February. 2025.

A non-inferiority, double-blind, randomized, active-controlled, 2-arm, parallel-group, Phase 3 study of biosimilar denosumab versus reference denosumab was conducted at 12 centers in Iran from April 2017 to August 2020. The patient received either 60 mg of the biosimilar (n=95) or the reference product (n=95) subcutaneously at baseline, month 6 and month 12. They were assessed at months 0, 1, 3, 6, 8, 12, 15 and 18.

The average age of patients assigned to the biosimilar was 61.6 years and the average age of the reference product group was 60.6 years. All patients were postmenopausal women. Baseline mean (SD) bone mineral density (BMD) at the lumbar spine was equivalent for the biosimilar and reference groups, at 0.71 (0.06); for the total hip, 0.79 (0.10) in the biosimilar group and 0.78 (0.11) in the reference group; and at the femoral neck, 0.64 (0.09) and 0.64 (0.08), respectively.

The mean percentage changes in BMD were 5.91% (5.58) in the biosimilar group and 5.52% (5.59%) in the reference group at the lumbar spine; 2.32% (5.24%) and 2.28% (5.52%), respectively, for the total hip; and 1.91% (6.32) and 1.50% (6.62%), respectively, at the femoral neck. “Differences between treatment groups were not statistically significant at any site,” the authors wrote.

The primary endpoint of non-inferiority of the biosimilar to the reference product was met. Additionally, there were no new vertebral fractures among the 190 patients in the study.

A total of 135 adverse events (AEs) were reported, the most common being metabolic and nutritional disorders and musculoskeletal and connective tissue disorders in both arms. Most (88%) of the AEs were classified as grade 1 or 2 and 11.8% were grade 3. There were no grade 4 AEs. In addition, 13 serious AEs (SAEs) were reported in 12 patients, all of whom resulted in hospitalization and were considered unrelated to treatment.

The overall incidence of AEs and SAEs was comparable between the 2 arms, the authors noted. However, they wrote that evaluating rare, long-term AEs, such as new fractures or osteonecrosis of the jaw, will require studies over a longer period.

Overall, the study demonstrated that the biosimilar denosumab was non-inferior to the reference product. “In general, there was no difference in the change in BMD percentage of the lumbar spine, total hip, or femoral neck; the evolution of biomarkers of bone metabolism; or the occurrence of new vertebral fractures between the biosimilar denosumab and the reference product”, conclude the authors.


Jamshidi A, Vojdanian M, Soroush M, et al. Efficacy and Safety of the Biosimilar Candidate Denosumab (Arylia) Compared to the Reference Product (Prolia) in Postmenopausal Osteoporosis: A Phase III, Randomized, Two-Arm, Double-Blind, Parallel, Agent-Controlled Clinical Trial active and non-inferior. Arthritis Res Ther. 2022;24(1):161. doi:10.1186/s13075-022-02840-8


Comments are closed.