FDA Approves 2 Additional Denosumab Biosimilars in Prior Indications

The denosumab biosimilars have been approved based on review of a comprehensive data package that showed no meaningful differences vs the already approved agents.

The FDA has approved denosumab-nxxp as a 60 mg/mL injection (Bildyos) and denosumab-nxxp as a 120 mg/1.7 mL injection (Bilprevda) as biosimilars to denosumab (Prolia) and denosumab (Xgeva), respectively, in all indications of the reference products, according to a press release from the developer, Shanghai Henlius Biotech.¹

Both biosimilars were approved based upon the review of a comprehensive data package, including structural and functional analytical data, clinical pharmacokinetic data, and a comparative study that demonstrated Bildyos and Bilprevda have no clinically meaningful differences vs their reference products regarding safety, purity, and potency.

“The FDA approvals of Bildyos and Bilprevda mark a significant step toward expanding access to critical bone care treatments needed by millions of [patients] in the US, including a growing aging population.^2-4 Our goal with these biosimilars is to improve access and affordability across multiple therapeutic areas, including for osteoporosis, which disproportionately affects women,” stated Jon Martin, the US commercial lead of Biosimilars and General Medicines at Organon, in the press release.^1,3,4 “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.”^3-5

Previously, in March 2025, the FDA approved 2 other biosimilars, denosumab-bmwo (Stobocolo) and denosumab-bmwo (Osenvelt), for all indications of Prolia and Xgeva, respectively.⁶

Bildyos

Bildyos, a RANK ligand inhibitor, as a 60 mg/ML injection, has been indicated for approval in all the indications for which Prolia was approved.

Those indications are for the treatment of postmenopausal women with osteoporosis at high risk for fracture, to increase bone mass in men with osteoporosis at high risk for fracture, for the treatment of glucocorticoid-induced osteoporosis in men and women at high risk for fracture, to increase bone mass in men at risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer, and to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.

Notably, patients with advanced kidney disease who were treated with Bildyos were at greater risk of severe hypocalcemia. In those with advanced chronic kidney disease, evaluation for the presence of chronic kidney disease-mineral bone disorder (CKD-MBD) should be conducted before initiation of therapy; therapy should also be supervised by a health care provider with expertise in the diagnosis and management of CKD-MBD.

The most common adverse reactions reported with denosumab products in women with postmenopausal osteoporosis include back pain, pain in extremity, and musculoskeletal pain; in men with osteoporosis, they were back pain, arthralgia, and nasopharyngitis; and in patients with glucocorticoid-induced osteoporosis, they were back pain, hypertension, and bronchitis. The most common adverse reactions leading to discontinuation of the denosumab product were back pain and constipation.

Bilprevda

Bilprevda, a RANK ligand inhibitor, as a 120 mg/1.7 mL injection, was indicated for approval in all indications for which Xgeva was approved.

Those indications include the prevention of skeletal-related events in certain patients with multiple myeloma and bone metastases from solid tumors, giant cell tumor of bone, and hypercalcemia of malignancy.

Hypersensitivity reactions, such as anaphylaxis, may occur with the use of denosumab products, including Bilprevda. Hypocalcemia levels should be corrected before initiation of Bilprevda, and calcium levels should be monitored, especially during the first weeks of initiating therapy.

The most common adverse reactions in patients with bone metastasis from solid tumors were fatigue/asthenia, hypophosphatemia, and nausea; in those with multiple myeloma, they were diarrhea, nausea, anemia, back pain, and thrombocytopenia; in those with giant cell tumor of bone, they were arthralgia, back pain, and pain in extremity; and in patients with hypercalcemia of malignancy, they were nausea, dyspnea, and decreased appetite.

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. News release. Shanghai Henlius Biotech. September 2, 2025. Accessed September 2, 2025. https://tinyurl.com/kypzynva
2. Office of Women’s Health. Osteoporosis. US Food and Drug Administration. May 13, 2024. Accessed September 2, 2025. https://tinyurl.com/yuu2fybu
3. Biosimilars in the United States: providing more patients greater access to lifesaving medicines. Biosimilars Council. 2017. Accessed September 2, 2025. https://tinyurl.com/2w4eeurw
4. Overview for health care professionals. US Food and Drug Administration. Updated August 1, 2024. Accessed September 2, 2025. https://tinyurl.com/5h7py6w4
5. Aitken M, Kleinrock M, Pritchett J. Biosimilars in the United States 2023-2027: competition, savings, and sustainability. IQVIA Institute for Human Data Science. January 31, 2023. Accessed September 2, 2025. https://tinyurl.com/pbmkzycd
6. Celltrion receives U.S. FDA approval for STOBOCLO® (denosumab-bmwo) and OSENVELT® (denosumab-bmwo) biosimilars referencing PROLIA® and XGEVA®. News release. Celltrion. March 4, 2025. Accessed September 2, 2025. https://tinyurl.com/ahnwrx57