FDA Approves 2 Biosimilars for Osteoporosis and Cancer-Related Bone Disease

The FDA has approved 2 biosimilars, denosumab-qbde (Enoby) and denosumab-qbde (Xtrenbo), referencing denosumab (Prolia) and denosumab (Xgeva), respectively, for use in all indications of the reference products.1

This approval follows the FDA approval of several other denosumab biosimilars in 2025,2 including:

Denosumab-kyqq (Bosaya) and (Aukelso) on September 17, 2025

Denosumab-nxxp (Bildyos) and (Bilprevda) on September 2, 2025

Denosumab-bmwo (Stobloco) and (Osenvelt) on March 4, 2025

Denosumab-bnht (Bomyntra) and (Conexxence) in March 2025

Denosumab-dssb (Ospomyv) and (Xbryk) on February 16, 2025

The approvals of Enoby and Xtrenbo were supported by a comprehensive package of analytical, nonclinical, and clinical data that were submitted to the FDA.1 Together, these data demonstrated that both biosimilars are highly similar to their respective reference products and exhibit no clinically meaningful differences in quality, efficacy, safety, or immunogenicity.

“We are proud to be able to bring these biosimilar options to health care providers and patients, improving affordability and access to these important therapies,” Bill Larkins, PhD, president of Hikma Injectables, shared in a news release. “We are a top-three United States [US] provider of sterile injectable medicines to US hospitals, and we will use our strong and well-established commercial capabilities to bring these products to patients.”

Enoby is indicated for:

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

The increase of bone mass in men receiving ADT for nonmetastatic prostate cancer who are at high risk for fracture

The increase of bone mass in women receiving adjuvant aromatase inhibitor therapy for breast cancer who are at high risk for fracture.

Xtrenbo is indicated for:

The prevention of skeletal-related complications in patients with bone metastases from solid tumors and patients with multiple myeloma

The treatment of adult and skeletally mature adolescent patients with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity

The treatment of patients with hypercalcemia of malignancy that is refractory to bisphosphonate therapy

“The approvals of Enoby and Xtrenbo represent a significant milestone accomplishment for Richter, as our first FDA approved biosimilars,” Erik Bogsch, PhD, head of the Biotechnology Business Unit at Richter, noted in the news release. “They are a testimony to Richter’s ambition in providing affordable biosimilar access in important therapies to patients across the globe and establishing Richter as a high-quality biosimilar developer and manufacturer.”

What Is the Known Safety Profile of the Denosumab Biosimilars Enoby and Xtrenbo?

The safety profiles of the biosimilars are consistent with those of their reference products, according to the news release. Common adverse effects (AEs) associated with Enoby include back pain, pain in extremity, hypercholesterolemia, musculoskeletal pain, cystitis, arthralgia, nasopharyngitis, hypertension, bronchitis, and headache. Common adverse effects (AEs) associated with Xtrenbo include fatigue, asthenia, hypophosphatemia, nausea, diarrhea, anemia, back pain, thrombocytopenia, peripheral edema, hypocalcemia, upper respiratory tract infection, rash, headache, pain in extremity, dyspnea, decreased appetite, vomiting, and constipation.3 More serious toxicities have also been reported, such as severe hypocalcemia and osteonecrosis of the jaw. Additional risks of serious AEs include fetal harm if used during pregnancy.

Both Prolia and Xgeva, along with their biosimilar counterparts, carry a boxed warning for life-threatening hypocalcemia in patients with advanced chronic kidney disease, especially those on dialysis.1,3 This risk is further heightened in patients with chronic kidney disease who also have mineral and bone disorder. For this reason, oncologists are advised to evaluate patients for chronic kidney disease and mineral and bone disorder before initiating treatment and to closely monitor calcium levels throughout therapy.

References

1. 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 September 30, 2025. 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/
2. Biosimilar Product Information. Updated September 29, 2025. Accessed September 30, 2025. https://www.fda.gov/drugs/biosimilars/biosimilar-product-information
3. 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 March 4, 2025. https://www.celltrion.com/en-us/company/media-center/press-release/3768