LY01011, Biosimilar of Denosumab, Meets Primary End Point in Study

Recent study findings published in the Journal of Bone Oncology show that LY01011 (Shandong Boan BioTechnology), a biosimilar to denosumab (Xgeva; Amgen), demonstrated equivalent efficacy and safety to its reference product when treating patients with bone metastases. Notably, there were no unexpected adverse events (AEs) observed during the study’s duration.¹

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Bone metastases, or the spread of cancer to the bones, are a serious concern for patients who have advanced cancer and present a burden to the health care system. Bones that are weakened by metastases are more prone to fractures and spinal cord compression and necessitate procedures (eg, major surgery, radiation) that are designed to prevent or manage such complications.^1,2

Denosumab is a bone antiresorptive medication that is FDA-approved for the preventative treatment of fracture, spinal cord compression, or the need for either radiation or surgery to bone in patients with multiple myeloma or those with bone metastases from solid tumors. Based on the results from 3 pivotal phase 3 trials, denosumab received its approval for the preventative treatment of bone metastases from solid tumors and skeletal-related events in November 2010.^1-3

In a previous phase 1 trial featuring healthy participants, LY01011 showed similar characteristics to those of denosumab in terms of pharmacokinetics, pharmacodynamics, safety, tolerance, and immunogenicity.¹ Other biosimilars of denosumab include denosumab-bmwo (Stoboclo; Celltrion), denosumab-bmwo (Osenvelt; Celltrion)⁴, denosumab-bnht (Conexxence, Bomyntra; Fresenius Kabi)⁵, denosumab-dssb 120-mg vial (Xbryk; Samsung Bioepis Co) and denosumab-dssb 60-mg prefilled syringe (Ospomyv; Samsung Bioepis Co), all of which are approved for all indications of the reference product.⁶

The current study (NCT04859569) was conducted to verify LY01011’s equivalence to denosumab when treating patients with bone metastasis from solid tumors. Enrolled patients were ages 18 to 80 years and had to have a solid tumor confirmed by pathological examination; at least 1 documented bone metastasis confirmed by computed tomography, magnetic resonance imaging, or pathology (bone biopsy); an Eastern Cooperative Oncology Group performance status of 2 or less; and adequate organ functions at baseline.¹

All 850 patients enrolled were randomly assigned to receive either 120 mg of LY01011 (n = 424) or denosumab (n = 426) subcutaneously every 4 weeks during a 12-week double-blind treatment period. Following this portion, all patients received LY01011 until week 53. The trial’s primary end point was the natural logarithm of change of the urinary N-terminal crosslinked telopeptide of type 1 collagen level normalized to the urine creatinine level (uNTX/uCr) at week 13 from baseline. Other end points included the following: uNTX/uCr ratio, serum bone-specific alkaline phosphatase level alteration, status of anti-drug antibodies and neutralizing antibodies, AEs, and serious AEs.¹

The findings demonstrated that the least-squares means of the natural logarithms of the changes in the uNTX/uCr ratios at week 13 from baseline were about −1.810 in the LY01011 group and −1.791 in the denosumab group. The difference between the 2 arms was about −0.019 (90% CI –0.110, 0.073) within the equivalence margins (90% CI −0.135, 0.135) and met the predetermined primary end point. Of note, AEs, antidrug antibodies, and the pharmacokinetic data showed no statistically significant difference.¹

During the 12-week double-blind treatment period, approximately 91.3% (n = 775) of patients had at least 1 treatment-emergent AE (TEAE; LY01011: 91.7%; n = 389; denosumab: 90.8%; n = 386). The most common TEAEs were decreased white blood cell count (32.5% vs. 34.8%, respectively) and neutrophil count (32.1% vs. 33.6%); anemia (30.7% vs. 28.7%); and hypocalcemia (20.3% vs. 18.4%). Of note, the proportions of patients with grade 3 or higher TEAEs (38.4% and 38.4%) and serious TEAEs (13.2% and 14.1%) were similar between the respective groups.¹

“A long-term follow-up study was not conducted in patients with bone metastasis from solid tumors," wrote the authors. "Considering its mechanism of action and substantial evidence from prior clinical studies, denosumab was unlikely to prolong overall survival. Therefore, the long-term observations of [skeletal-related events] and overall survival might not be necessary for a comparable biosimilar study."¹

REFERENCES

1. Zhao M, Hu X, Zhuang P, et al. A multicenter, randomized, double-blind trial comparing LY01011, a biosimilar, with denosumab (Xgeva®) in patients with bone metastasis from solid tumors. J of Bone Oncol. 2025;51:100661. doi:10.1016/j.jbo.2025.100661

2. Amgen. FDA Approves Amgen's XGEVA(TM) (Denosumab) for the Prevention of Skeletal-Related Events in Patients with Bone Metastases from Solid Tumors. News release. November 18, 2010. Accessed August 20, 2025. https://www.amgen.com/newsroom/press-releases/2010/11/fda-approves-amgens-xgevatm-denosumab-for-the-prevention-of-skeletalrelated-events-in-patients-with-bone-metastases-from-solid-tumors

3. Hildebrand GK, Patel P, Kasi A. Denosumab. National Library of Medicine. Updated February 28, 2024. Accessed August 20, 2025. https://www.ncbi.nlm.nih.gov/books/NBK535388/

4. Halpern L. FDA Approves Biosimilars Referencing Denosumab for Osteoporosis-, Cancer-Related Skeletal Events. Pharmacy Times. March 4, 2025. Accessed August 20, 2025. https://www.pharmacytimes.com/view/fda-approves-biosimilars-referencing-denosumab-for-osteoporosis--cancer-related-skeletal-events

5. Ferruggia K. Denosumab-bnht Biosimilar Receives FDA Approval. Pharmacy Times. March 27, 2025. Accessed August 20, 2025. https://www.pharmacytimes.com/view/denosumab-bnht-biosimilar-receives-fda-approval

6. Halpern L. FDA Approves Biosimilar Denosumab-dssb to Treat Osteoporosis-, Cancer-Related Bone Loss. Pharmacy Times. February 17, 2025. Accessed August 20, 2025. https://www.pharmacytimes.com/view/fda-approves-biosimilar-denosumab-dssb-to-treat-osteoporosis--cancer-related-bone-loss