CHMP Shares Positive Opinion for Denosumab Biosimilars for Osteoporosis and Skeletal-Related Cancer Complications

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has issued a positive opinion regarding the applications for 2 denosumab biosimilar candidates for use in all indications of the denosumab reference products (Prolia) and (Xgeva

Denosumab Biosimilars |
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), including osteoporosis and cancer-related bone conditions.¹

The biosimilars were developed by Fresenius Kabi.

“The CHMP positive opinion marks an important step in Fresenius Kabi’s efforts to enhance patient access to biosimilar products and expand its capabilities and portfolio in biosimilars development,” according to a news release.

In the United States, Prolia is indicated for²:

• Use in postmenopausal women with osteoporosis at high risk for fracture
• To increase bone mass in men with osteoporosis at high risk for fracture
• To manage glucocorticoid-induced osteoporosis in men and women at high risk for fracture
• To increase bone mass in men at high risk for fracture who are receiving androgen deprivation therapy for the management of nonmetastatic prostate cancer
• To increase bone mass in women at high risk for fracture who are receiving adjuvant aromatase inhibitor therapy for the management of breast cancer

Contraindications to Prolia use include hypocalcemia, pregnancy, and known hypersensitivity to Prolia. The Prolia prescribing information notes that during Prolia use, pre-existing hypocalcemia may worsen, especially in patients with renal impairment; hypersensitivity, including anaphylactic reactions, may occur; serious infections, including skin infections, may occur; severe bone, joint, and muscle pain may occur. Additionally, osteonecrosis of the jaw, atypical femoral fractures, dermatologic reactions, and significant suppression of bone turnover have been reported with Prolia use. Additionally, multiple vertebral fractures have been reported following Prolia discontinuation. Patients receiving Prolia should not concomitantly receive other denosumab products; this agent is administered at 60 mg/mL via a single-dose prefilled syringe.

Xgeva is indicated for³:

• To prevent skeletal-related events in patients with multiple myeloma and patients with bone metastases from solid tumors
• To treat adult and skeletally mature adolescent patients with giant cell tumor of the bone that is unresectable or where surgical resection is likely to result in severe morbidity
• To manage hypercalcemia of malignancies that are refractory to bisphosphonate therapy

Contraindications to Xgeva use include hypocalcemia and known clinically significant hypersensitivity to Xgeva or other denosumab products. The Xgeva prescribing information notes that during Xgeva use, hypersensitivity reactions, including anaphylaxis, may occur; and that severe symptomatic hypocalcemia may occur, fatal cases of which have been reported; Additionally, osteonecrosis of the jaw has been reported with Xgeva use. Following treatment discontinuation, hypercalcemia may arise in patients with giant cell tumor of bone and/or patients with growing skeletons; and multiple vertebral fractures may occur. Patients receiving Xgeva should not concomitantly receive other denosumab products. This agent is administered in a 70 mg/mL solution via a single-dose vial.

Notably, on March 26, 2025, the FDA approved the denosumab-bnht biosimilars (Conexxence) and (Bomyntra) for use in all indications of the reference products Prolia and Xgeva, respectively.⁴ This regulatory decision was backed by findings from similarity and analytical development assessments that were supported by data from 2 comparative clinical trials. One trial was a pharmacodynamic, pharmacokinetic, and immunogenicity study in healthy volunteers. The other study evaluated efficacy, safety, pharmacodynamics, and immunogenicity in women with postmenopausal osteoporosis.

Previously, on March 4, 2025, the FDA approved the denosumab-bmwo biosimilars (Stobloco) and (Osenvelt) for use in all indications of the denosumab reference products Prolia and Xgeva, respectively.⁵ This regulatory decision was supported by data from a phase 3 trial (NCT04757376) that investigated the efficacy, pharmacodynamics, pharmacokinetics, safety, and immunogenicity of denosumab-bmwo compared with reference denosumab.

References

1. Denosumab CHMP positive opinion. News release. Fresenius. May 27, 2025. Accessed June 3, 2025. https://www.fresenius.com/node/7097
2. Prolia. Prescribing information. Amgen, May 2025. Accessed June 3, 2025. https://www.pi.amgen.com/-/media/Project/Amgen/Repository/pi-amgen-com/Prolia/prolia_pi.pdf
3. Xgeva. Prescribing information. Amgen, May 2025. Accessed June 3, 2025. https://www.pi.amgen.com/-/media/Project/Amgen/Repository/pi-amgen-com/Prolia/prolia_pi.pdf
4. 4.Fresenius receives FDA approval for their Denosumab biosimilars and secures global settlement agreement. News release. Fresenius. March 26, 2025. Accessed June 3, 2025. https://www.fresenius-kabi.com/news/fda-approval-for-denosumab-biosimilars
5. Celltrion receives U.S. FDA approval for Stoboclo (denosumab-bmwo) and Osenvelt (denosumab-bmwo) biosimilars referencing Prolia and Xgeva. Celltrion. March 4, 2025. Accessed June 3, 2025. https://www.celltrion.com/en-us/company/media-center/press-release/3768