Denosumab Biosimilar Noninferior to Reference Product in Postmenopausal Women

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

Compared with the reference product, the efficacy of a denosumab biosimilar candidate (Arylia developed by AryoGen Pharmed in Iran) is noninferior and the safety was comparable after 18 months, according to a study published in Arthritis Research & Therapy. Currently, there are no FDA-approved biosimilars to treat osteoporosis, although the European Medicines Agency granted marketing authorization for a teriparatide biosimilar in 2017. In the United States, patents for denosumab (marketed as Prolia and Xgeva depending on the indication) expire in February 2025.

A double-blind, randomized, active-controlled, 2-armed, parallel-group, noninferiority, phase 3 study of biosimilar denosumab vs reference denosumab was conducted in 12 centers in Iran from April 2017 to August 2020. Patient either received 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 for the reference product group was 60.6 years. All of the patients were postmenopausal women. The mean (SD) baseline bone mineral density (BMD) at the lumbar spine was equivalent for the biosimilar and reference groups, at 0.71 (0.06); for 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 percent 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 total hip; and 1.91%% (6.32) and 1.50% (6.62%), respectively, at the femoral neck. “The differences between the treatment groups were not statistically significant at either site,” the authors wrote.

The primary end point of noninferiority of the biosimilar vs the reference product was met. In addition, there were no new vertebral fractures among the 190 patients participating in the study.

A total of 135 adverse events (AEs) were reported, with the most common being metabolism and nutrition disorders and musculoskeletal and connective tissue disorders in both arms. Most (88%) AEs were categorized as grade 1 or 2 and 11.8% were grade 3. There were no grade 4 AEs. In addition, there were 13 serious AEs (SAEs) reported in 12 patients, all of which 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 and long-term AEs, such as new fractures or osteonecrosis of the jaw, will require studies over a more prolonged period of time.

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

Reference

Jamshidi A, Vojdanian M, Soroush M, et al. 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. Arthritis Res Ther. 2022;24(1):161. doi:10.1186/s13075-022-02840-8