FDA Issues REMS Guidance for Hypocalcemia Risk Associated With 2 Denosumab Biosimilars

The FDA has issued safety updates under the Risk Evaluation and Mitigation Strategy (REMS) program for the biosimilars denosumab-qbde (Enoby) and denosumab-dssb (Ospomyv), which both reference denosumab (Prolia).^1,2

The REMS updates for both biosimilars emphasize the increased risk for severe hypocalcemia following administration in patients with advanced chronic kidney disease, defined as those with estimated glomerular filtration rate levels below 30 mL/min/1.73 m², including patients dependent on dialysis. The updates note that cases of severe hypocalcemia resulting in life-threatening events, hospitalization, and death have been reported.

How can the risk of severe hypocalcemia be minimized in patients with advanced chronic kidney disease receiving Enoby and Ospomyv?

The safety updates indicate that health care providers should assess patients for the presence of chronic kidney disease mineral and bone disorder, including those with intact parathyroid hormone, serum calcium, 25(OH) vitamin D, and 1,25 (OH)₂ vitamin D levels, before deciding whether to treat with either of these biosimilars. Providers should also consider evaluating bone turnover status via bone biopsy or serum markers of bone turnover to identify the possible presence of underlying bone disease.

After the administration of Enoby or Ospomyv to patients who are fit to receive this therapy, providers should monitor serum calcium levels on a weekly basis during the first month after administration, as well as every month thereafter. If treating patients with advanced chronic kidney disease, providers should also coordinate patient care with input from providers who have expertise in managing chronic kidney disease mineral and bone disorder.

How can health care providers counsel patients about the safe use of Enoby and Ospomyv?

The safety updates highlight that health care providers should give each patient a copy of the patient guide for the agent they are receiving; review the information in the guides with each patient, including the serious risks associated with the agents and the symptoms of severe hypocalcemia; and recommend that each patient seek immediate medical attention if they develop symptoms or signs of severe hypocalcemia.

What are the FDA-approved treatment indications for Enoby and Ospomyv?

Enoby and Ospomyv are both indicated for use in all indications of their reference product, which include:

• The increase of bone mass in women receiving adjuvant aromatase inhibitor therapy for breast cancer who are at high risk for fracture
• The increase of bone mass in men receiving androgen deprivation therapy for nonmetastatic prostate cancer who are at high risk for fracture
• The management of osteoporosis in postmenopausal women at high risk for fracture
• The increase of bone mass in men with osteoporosis at high risk for fracture
• The management of glucocorticoid-induced osteoporosis in patients at high risk for fracture^3,4

What are the regulatory histories of Enoby and Ospomyv?

Notably, Enoby was approved by the FDA on September 30, 2025, in conjunction with a simultaneous approval for denosumab-qbde (Xtrenbo), a biosimilar referencing denosumab (Xgeva).⁵ This regulatory decision was supported by a comprehensive collection of nonclinical, clinical, and analytical data that were submitted to the FDA.

Ospomyv was approved by the FDA on February 17, 2025, in conjunction with a simultaneous approval for denosumab-dssb (Xbryk), a biosimilar referencing denosumab (Xgeva).⁴ This regulatory decision was backed by findings from a phase 1 trial (NCT06095427) that investigated the use of the denosumab biosimilar LY06006 compared with US- and EU-sourced denosumab in healthy male patients.

References

1. Enoby REMS FDA required REMS safety information. News release. Hikma Pharmaceuticals USA Inc. January 2026. Accessed February 12, 2026. https://syneoshealth4.my.salesforce.com/sfc/p/#5f000001BTYC/a/Ka0000015lsX/3GldqJ6UgqU44rYrvig5Pv5uOSHq.ZiOdOAy7aFO0pU
2. FDA-required REMS safety information / important safety notice. Samsung Bioepis Co., Ltd. Accessed February 12, 2026. https://syneoshealth4--ospomyvdev.sandbox.my.salesforce.com/sfc/p/#Dg0000001rel/a/Dg0000004vVM/D11SKkbu3lf8x8M2aiKEKjAMqn_b64mEsDVBLiN64Y4
3. Enoby. Prescribing information. FDA. September 2025. Accessed February 12, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761439s000lbl.pdf
4. FDA approves Samsung Bioepis’ Ospomyv, Xbryk (denosumab-dssb), a biosimilar to Prolia and Xgeva. News release. Samsung Bioepis Co., Ltd. February 16, 2025. Accessed February 12, 2026. https://www.samsungbioepis.com/en/newsroom/newsroomView.do?idx=435&currentPage=1
5. Hikma and Richter receive FDA approval for denosumab biosimilars Enoby (denosumab- qbde) and Xtrenbo (denosumab- qbde) referencing Prolia and Xgeva respectively. News Release. Hikma. September 29, 2025. Accessed February 12, 2026. https://www.hikma.com/news/hikma-and-richter-receive-fda-approval-for-denosumab-biosimilars-enobytm-denosumab-qbde-and-xtrenbotm-denosumab-qbde-referencing-prolia-and-xgeva-respectively/