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Denosumab Biosimilar Demonstrates Positive Safety Results in Chinese Study


A Chinese randomized study in healthy participants found comparable pharmacokinetic, pharmacodynamic, and safety profiles between LY01011, a denosumab biosimilar, and its originator (Xgeva).

bone cancer | Image credit: catalin - stock.adobe.com

Advanced malignancies commonly metastasize into bones. The most common tumors prone to bone metastasis are in breast cancer, prostate cancer, lung cancer, renal cancer, and multiple myeloma.

LY01011, a denosumab biosimilar candidate, was found to have comparable pharmacokinetic (PK), pharmacodynamic (PD), and safety profiles with its originator (Xgeva) when administered to healthy Chinese participants in a recent study.

The single-center, randomized, double-blind, single-dose, active comparator, parallel-controlled analysis, published in Journal of Bone Oncology, did not identify any unexpected drug-related safety signals in either group but did demonstrate similar immunogenicity between the products.

Advanced malignancies commonly metastasize into bones. The most common tumors prone to bone metastasis are in breast cancer, prostate cancer, lung cancer, renal cancer, and multiple myeloma. Denosumab is a receptor activator of nuclear Κ-B ligand and an essential cytokine responsible for osteoclast activation and differentiation, making it a great alternative to common treatments for bone metastases. Common treatments—such as biphosphates, hormone therapy, and chemotherapy—are often less effective, lead to nephrotoxicity, and require less convenient dose administration.

In the study, 625 healthy Chinese participants were screened, 168 of whom were randomized 1:1 to receive a single subcutaneous administration of 120 mg of the biosimilar (n = 85) or reference product (n = 83). The mean (SD) age of the cohorts were 36.6 (8.2) years in the biosimilar group and 37.1 (8.1) years in the Xgeva group. Most participants in both groups were women (55.3% vs 57.8%, respectively). Blood samples were taken and evaluated to identify PK, PD, and immunogenicity parameters. Safety profiles were evaluated based on number of adverse events (AE), including treatment emergent AEs (TEAEs) and serious AEs (SAEs).

The geometric mean range (GMR) for maximum plasma concentration (Cmax), area under the concentration–time curve from time zero to last quantifiable concentration (AUC0→t), and AUC from time zero to infinity (AUC0→∞) were 98.1%, 100.3% and 100.39%, respectively, all of which met the predefined acceptance range for 95% CI between 80% and 125%.

For the PD markers, the mean AUC0→t values for LY01011 and denosumab groups were 19,376.4 and 19,634.1, respectively. The mean maximum effect (Emax) values for LY01011 and reference product groups were 87.654% and 87.759%, respectively. The median time to achieve Emax values for LY01011 and reference product groups were 69 and 83 days, respectively. The PD parameters were consistent with the PK parameters, indicating that LY01011 and denosumab had similar pharmacodynamic effects in healthy Chinese subjects.

A total of 282 grade 1 TEAEs were reported in the biosimilar group, and 266 were reported in the reference product group. Additionally, 14 participants in each group experienced grade 2 TEAEs (LY01011, n = 19; reference product, n = 20). The majority of the study TEAEs were categorized as grade 1 in severity, and most patients fully recovered. No grade 3 or above TEAEs were reported in either group. The severities of TEAEs between the treatment groups were also comparable.

Three subjects reported SAEs, which led to the subject withdrawing from the study. Of 6 SAEs, 1 case each of contusion, neck injury, head injury, and lumbar vertebral fracture were reported in LY01011 group, whereas 1 case each of ectopic pregnancy and scrotal injury were observed in the reference product group. All SAEs leading to the subject withdrawal from the study were deemed to be unlikely related to the study drug.

Although the authors didn’t list study limitations, the study was conducted in healthy Chinese subjects, and the results may not be generalizable to other populations or patient groups. Additionally, the study was a single-dose study, and the safety and efficacy of LY01011 compared with denosumab in a multiple-dose setting remain to be evaluated. Finally, the study was conducted in a relatively small sample size, and larger studies may be needed to confirm the findings of this study.


Ding Y, Liu Y, Dou C, Guo S. A randomized trial comparing LY01011, biosimilar candidate, with the reference product denosumab (Xgeva) in healthy Chinese subjects. J Bone Oncol. Published online September 1, 2023. doi:10.1016/j.jbo.2023.100499

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