FDA Approves Denosumab Biosimilars for Osteoporosis and Cancer-Related Bone Events

The US FDA has granted approval for Bildyos and Bilprevda, 2 biosimilars to denosumab, a monoclonal antibody targeting the receptor activator of nuclear factor kappa-B ligand (RANKL), for the treatment of osteoporosis and cancer-related bone loss.¹

These approvals mark a significant expansion in the availability of therapeutic options for managing a range of bone-related conditions, including postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, and the prevention of skeletal-related events in patients with multiple myeloma and bone metastases from solid tumors.

The approvals were based on a comprehensive review of data demonstrating that denosumab-nxxp is highly similar to its reference products, Prolia (for Bildyos) and Xgeva (for Bilprevda), with no clinically meaningful differences in terms of safety, purity, or potency. This finding is consistent with the established regulatory pathway for biosimilar approval, which relies on a totality-of-the-evidence approach rather than requiring new, large-scale phase 3 efficacy trials. The availability of these biosimilars is expected to increase patient access and potentially reduce health care costs, providing clinicians with more choices for patient care.

“The FDA approvals of Bildyos and Bilprevda mark a significant step toward expanding access to critical bone care treatments needed by millions of people in the US, including a growing aging population. Our goal with these biosimilars is to improve access and affordability across multiple therapeutic areas, including for osteoporosis, which disproportionately affects women,” said Jon Martin, US commercial lead, Biosimilars and General Medicines at Organon, in a press release. “This approval underscores Organon’s unwavering commitment to making treatments more accessible while focusing on creating a more sustainable future for the care of bone health.”

These approvals follow the March 2025 clearances of Stobloco and Osenvelt, 2 other denosumab biosimilars also referencing Prolia and Xgeva.²

Indications and Clinical Utility

Bildyos is indicated for the treatment of osteoporosis in postmenopausal women and men at high risk of fracture.¹ It is also approved for the treatment of glucocorticoid-induced osteoporosis in patients at high risk of fracture, as well as for increasing bone mass in men at high risk of fracture receiving androgen deprivation therapy (ADT) for nonmetastatic prostate cancer and in women at high risk of fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.

The mechanism of action involves inhibiting RANKL, which is essential for osteoclast formation, function, and survival. By blocking this pathway, denosumab reduces bone resorption and increases bone mineral density.

Bilprevda is approved for the prevention of skeletal-related events in patients with multiple myeloma and in those with bone metastases from solid tumors. It is also indicated for the treatment of giant cell tumor of bone in adults and skeletally mature adolescents and for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy. Its role in oncology-related bone disease stems from its ability to prevent osteoclast-mediated bone destruction, thereby reducing the incidence of pathologic fractures, radiation to bone, spinal cord compression, and the need for surgery.

Safety and Adverse Event Profile

As with its reference products, denosumab-nxxp carries important safety warnings that clinicians must consider. The most significant adverse event is severe hypocalcemia, particularly in patients with preexisting hypoparathyroidism, thyrotoxicosis, or chronic kidney disease. It is critical to correct hypocalcemia prior to administration and to monitor serum calcium levels closely during treatment.

Osteonecrosis of the jaw is another serious risk, especially in the oncology setting. The risk is higher in patients with poor oral hygiene, those with preexisting dental disease, or those receiving chemotherapy or corticosteroids. Atypical femoral fractures have also been reported with denosumab use. Patients should be advised to report any new or unusual thigh, hip, or groin pain.

Upon discontinuation of denosumab, there is a risk of multiple vertebral fractures, particularly in patients with a history of vertebral fracture. The FDA recommends close monitoring of patients for signs and symptoms of vertebral fractures after stopping therapy.

REFERENCES:

1. US Food and Drug Administration (FDA) Approves Henlius and Organon’s BILDYOS® (denosumab-nxxp) and BILPREVDA® (denosumab-nxxp), Biosimilars to PROLIA (denosumab) and XGEVA (denosumab), Respectively. Henlius Biotech. September 2, 2025. Accessed September 3, 2025. https://tinyurl.com/y9sh9jaz

2. Celltrion receives U.S. FDA approval for STOBOCLO® (denosumab-bmwo) and OSENVELT® (denosumab-bmwo) biosimilars referencing PROLIA® and XGEVA®. Prnewswire.com. March 3, 2025. Accessed September 3, 2025. https://tinyurl.com/yv8hp2s6