FDA Approves 2 New Denosumab Biosimilars

The FDA has approved new denosumab biosimilars, denosumab-desu (Osvyrti and Jubereq), for the treatment of osteoporosis and management of skeletal-related events in cancer.¹

These approvals provide new therapeutic options clinically equivalent to the reference products, Prolia and Xgeva. Osvyrti is interchangeable with Prolia, while Jubereq is interchangeable with Xgeva. Both agents are human monoclonal antibodies that bind to RANKL, inhibiting osteoclast formation and reducing bone resorption.

Indications and Usage

Osvyrti is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture and to increase bone mass in men with osteoporosis at high risk for fracture. It is also approved for the treatment of glucocorticoid-induced osteoporosis in men and women at high risk for fracture, as well as to increase bone mass in men receiving androgen deprivation therapy for nonmetastatic prostate cancer and women receiving adjuvant aromatase inhibitor therapy for breast cancer.

Jubereq is indicated for the prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors. Additional indications include the treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity, and the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy.

Clinical Trial Data

The FDA approvals were based on a comprehensive data package confirming biosimilarity, including results from a pivotal phase 3 clinical trial and a phase 1 pharmacokinetic study.

The phase 3 trial (NCT05419427) was a randomized, double-blind, active-controlled, parallel-arm multicenter study evaluating the efficacy, safety, and immunogenicity of the biosimilar compared with the reference product in postmenopausal women with osteoporosis.² The study met its primary end points, demonstrating that Osvyrti is highly similar to the reference product with no clinically meaningful differences in pharmacokinetics, pharmacodynamics, safety, or efficacy.

Additionally, a phase 1 randomized, double-blind, 3-arm pharmacokinetic study in healthy adult males compared Jubereq with the reference product Xgeva.The study confirmed comparable pharmacokinetic parameters between the biosimilar and the reference product.¹

Safety and Boxed Warnings

The safety profiles of both biosimilars are consistent with their respective reference products. Prescribing information for Osvyrti and Jubereq includes a boxed warning regarding the risk of severe hypocalcemia in patients with advanced chronic kidney disease, particularly those on dialysis. Severe hypocalcemia in these patients can lead to hospitalization, life-threatening events, and death.

Other warnings and precautions include the risk of osteonecrosis of the jaw, atypical femoral fractures, multiple vertebral fractures following discontinuation of treatment, and hypersensitivity reactions.

Common adverse reactions reported in trials for the osteoporosis indication included back pain, pain in extremity, musculoskeletal pain, hypercholesterolemia, and cystitis. For the oncology indications, common adverse reactions included fatigue, hypophosphatemia, and nausea.

Market Context

"Both Osvyrti and Jubereq have been approved for a wide variety of bone-related indications," said Chrys Kokino, president of Accord BioPharma North America, in a statement. "These biosimilars have the potential to provide a large number of patients with treatment alternatives that lessen cost as a barrier to accessing proven therapies."

So far this year, the FDA has also approved Bosaya, Bildyos, and Stobloco as biosimilars for Prolia and Aukelso, Bilprevda, and Osenvelt as biosimilars for Xgeva.^3–5

REFERENCES

1. Accord BioPharma, Inc. Announces FDA Approval of Denosumab Biosimilars OSVYRTI® (denosumab-desu) and JUBEREQ® (denosumab-desu). News release. Accord BioPharma. November 20, 2025. Accessed November 20, 2025. https://tinyurl.com/35xfun86

2. Denosumab Biosimilar Injection in Post Menopausal Women With Osteoporosis. ClinicalTrials.gov. Updated October 13, 2023. Accessed November 20, 2025. https://clinicaltrials.gov/study/NCT05419427

3. Biocon Biologics Receives U.S. Food and Drug Administration Approval for Bosaya™ and Aukelso™, Denosumab Biosimilars. News release. Biocon Biologics. September 17, 2025. Accessed November 20, 2025. https://tinyurl.com/4r59a2n8

4. 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 November 20, 2025. https://tinyurl.com/y9sh9jaz

5. 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 November 20, 2025. https://tinyurl.com/yv8hp2s6