FDA Approves Denosumab Biosimilar for Skeletal-Related Events, GCTB, and Hypercalcemia of Malignancy

The FDA has approved denosumab-adet (Degevma) as a biosimilar to denosumab (Xgeva) for all indications of the reference product, including the prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors, according to a news release from Teva Pharmaceuticals.¹

The biosimilar is also approved for 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, as well as for hypercalcemia of malignancy refractory to bisphosphonate therapy. Denosumab-adet is supplied as a 120-mg/1.7-mL solution for injection in a single vial

The approval follows the FDA's March 2026 approval of denosumab-adet (Ponlimsi) as a biosimilar to denosumab (Prolia), giving Teva a US denosumab biosimilar portfolio that spans the indications of both reference products.^1,2 According to the company, the two agents are expected to launch in the United States in the coming months.¹

"The last thing a person living with a cancer diagnosis or their families should have to worry about is access to their medicine," Thomas Rainey, senior vice president of US Biosimilars at Teva, stated in a news release.¹

What evidence supported the FDA approval of denosumab-adet?

The approval was based on a totality of evidence, including analytical and clinical data demonstrating similar efficacy, safety, and immunogenicity between denosumab-adet and reference denosumab. The company stated that the data showed no clinically meaningful differences from Xgeva in terms of safety, purity, and potency.

Teva's clinical development program for its denosumab biosimilar candidate, TVB-009P, included a randomized, double-blind, multinational phase 3 study (NCT04729621) comparing the biosimilar candidate with reference denosumab (Prolia) in postmenopausal women with osteoporosis.³

Patients (n = 332) 60 to 90 years of age with a lumbar spine T score below –2.5 but not below –4.0 were randomly assigned to receive 60 mg of either agent subcutaneously every 26 weeks. The primary end point was percent change from baseline in lumbar spine bone mineral density at week 52; secondary end points included changes in serum C-telopeptide of type 1 collagen, femoral neck and total hip bone mineral density, and incidence of antidrug antibodies. At week 52, patients in the reference arm were rerandomized 1:1 to continue reference denosumab or transition to the biosimilar to assess immunogenicity and safety after switching.

What is the mechanism of action of denosumab-adet?

Denosumab-adet is a human IgG2 monoclonal antibody that binds to receptor activator of nuclear factor kappa-B ligand (RANKL), inhibiting osteoclast formation, function, and survival. This reduces bone resorption in cortical and trabecular bone and decreases cancer-induced bone destruction. The biosimilar is also approved in the European Union.

What is the safety profile of denosumab-adet in patients with bone metastases and multiple myeloma?

Denosumab-adet does not carry a boxed warning. Pre-existing hypocalcemia must be corrected before treatment initiation, and the agent is contraindicated in patients with known clinically significant hypersensitivity to denosumab products. Patients receiving denosumab-adet should not receive other denosumab products concomitantly.

Warnings and precautions include hypersensitivity reactions, including anaphylaxis; severe, symptomatic hypocalcemia, with fatal cases reported; osteonecrosis of the jaw; atypical femoral fractures; hypercalcemia following treatment discontinuation in patients with giant cell tumor of bone and in patients with growing skeletons; multiple vertebral fractures following discontinuation; and embryo-fetal toxicity. The risk of hypocalcemia is greater in patients with a creatinine clearance below 30 mL/min or those receiving dialysis, and calcium levels should be monitored, particularly during the first weeks of treatment.

In patients with bone metastases from solid tumors, the most common adverse effects were fatigue/asthenia, hypophosphatemia, and nausea; the most common serious adverse effect was dyspnea. In patients with multiple myeloma, the most common adverse effects were diarrhea, nausea, anemia, back pain, thrombocytopenia, peripheral edema, hypocalcemia, upper respiratory tract infection, rash, and headache; the most common serious adverse effect was osteonecrosis of the jaw.

References

1. Teva Pharmaceuticals. Teva continues biosimilar momentum with U.S. FDA approval of Degevma (denosumab-adet), a biosimilar to Xgeva (denosumab). News release. September 28, 2026. Accessed September 29, 2026. https://ir.tevapharm.com/news-and-events/press-releases/press-release-details/2026/Teva-Continues-Biosimilar-Momentum-with-U-S--FDA-Approval-of-DEGEVMA-denosumab-adet-a-Biosimilar-to-Xgeva-denosumab/default.aspx
2. Denosumab-adet gains FDA approval for all indications of denosumab. OncLive. March 30, 2026. Accessed September 29, 2026. https://www.onclive.com/view/denosumab-adet-gains-fda-approval-for-all-indications-of-denosumab
3. A randomized, double-blind, multinational, multicenter study to compare efficacy, safety, and immunogenicity of TVB-009P and denosumab (Prolia) in patients with postmenopausal osteoporosis. ClinicalTrials.gov. Accessed September 29, 2026. https://clinicaltrials.gov/study/NCT04729621