FDA Greenlights Fifth Pair of Denosumab Biosimilars: Bildyos and Bilprevda

The competitive landscape for bone health treatments in the US has intensified with the FDA approval of Bildyos (denosumab-nxxp) and Bilprevda (denosumab-nxxp), biosimilars to Amgen’s reference products Prolia and Xgeva, respectively.1

The approval, granted to Shanghai Henlius Biotech and Organon, marks the fifth pair of denosumab biosimilars to receive FDA clearance, promising to further expand access to more affordable treatment options for millions of patients facing osteoporosis and cancer-related bone complications.

Denosumab is a crucial therapeutic agent, functioning as a human monoclonal antibody that binds to the RANKL protein, thereby preventing the activation of the RANK receptor on osteoclasts and inhibiting osteoclastic bone resorption. The reference products, Prolia and Xgeva, are widely used for various bone-related conditions, including osteoporosis, bone metastases, hypercalcemia of malignancy, and giant cell tumor of bone. The introduction of multiple biosimilars is expected to drive down costs and improve patient access.

A Rapidly Expanding Market

The journey of denosumab biosimilars to the US market began relatively recently, with a flurry of approvals over the past year and a half:

Sandoz's Wyost and Jubbonti (denosumab-bddz for both) received FDA approval in March 2024, becoming the first biosimilars to reference Xgeva and Prolia, respectively, in the US.2

Both Wyost and Jubbonti were also granted interchangeability designations with their reference products, allowing for pharmacy-level substitution without requiring prior physician approval. At the time of their approval, there were no denosumab biosimilars approved in the European Union. These biosimilars were the first denosumab biosimilars to launch in the US in June 2025.3

In February 2025, Samsung Bioepis' Ospomyv and Xbryk (denosumab-dssb for both; SB16) gained approval from both the FDA and the European Medicines Agency (EMA).4 This pair also received an interchangeability designation and is currently "waiting in the wings to launch" in the US. Ospomyv references Prolia, and Xbryk references Xgeva.

Following this, the FDA approved Celltrion's Stoboclo and Osenvelt (denosumab-bmwo for both) on March 4, 2025. Stoboclo references Prolia, and Osenvelt references Xgeva. These biosimilars launched in the US in July 2025.

Fresenius Kabi's Conexxence and Bomyntra (denosumab-bnht for both) also received FDA approval in March 2025.5 Conexxence references Prolia, and Bomyntra references Xgeva. These biosimilars were approved for all indications of their respective reference products. Fresenius Kabi announced the commercial availability of these products in the US on July 1, 2025, and also plans to launch in Europe in the second half of 2025, pending regulatory approvals.

Henlius and Organon's Comprehensive Approval

The newest additions, Bildyos (denosumab-nxxp) and BILPREVDA (denosumab-nxxp), have been approved for all indications of their respective reference products.1 This broad approval was based on a comprehensive data package, including structural and functional analytical data, clinical pharmacokinetic data, and a comparative clinical study demonstrating that Bildyos and Bilprevda are highly similar to and have no clinically meaningful differences from their reference products, Prolia and Xgeva, respectively, in terms of safety, purity, and potency.

Bildyos, referencing Prolia, is indicated for:

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

Bildyos is supplied as a 60 mg/mL injection. A boxed warning regarding severe hypocalcemia in patients with advanced chronic kidney disease (CKD), including those on dialysis, accompanies Bildyos, and treatment in these individuals should be supervised by a health care provider with expertise in CKD-MBD.

Bilprevda, referencing Xgeva, is approved for:

• The prevention of skeletal-related events in patients with multiple myeloma and bone metastases from solid tumors.
• The treatment of giant cell tumor of bone in adults and skeletally mature adolescents where surgical resection is unresectable or likely to result in severe morbidity.
• The treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy. Bilprevda is available as a 120 mg/1.7 mL injection.

Safety concerns for Bilprevda include hypersensitivity reactions, severe symptomatic hypocalcemia, osteonecrosis of the jaw, atypical subtrochanteric and diaphyseal femoral fractures, multiple vertebral fractures following treatment discontinuation, and embryo-fetal toxicity, necessitating effective contraception for females of reproductive potential.

Although the sources highlighted interchangeability status for Sandoz's and Samsung Bioepis' products, there was no mention of an interchangeability designation for Henlius and Organon's Bildyos and Bilprevda in the provided information.

Jon Martin, US commercial lead for biosimilars and general medicines at Organon, emphasized the significance of these approvals, stating, "Our goal with these biosimilars is to improve access and affordability across multiple therapeutic areas, including for osteoporosis, which disproportionately affects women."

Jason Zhu, PhD, executive director and CEO of Henlius, added that the approvals underscore their commitment to "expanding access to quality biologics... delivering biosimilar treatment options that are as safe and effective as the reference biologics to more patients across the US."

References

1. Shanghai Henlius Biotech, Inc. 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-media. September 2, 2025. Accessed September 2, 2025. https://www.henlius.com/en/NewsDetails-5427-26.html

2. Jeremias S. FDA approves first denosumab biosimilars. The Center for Biosimilars®. March 5, 2024. Accessed September 2, 2025. https://www.centerforbiosimilars.com/view/fda-approves-first-denosumab-biosimilar

3. Jeremias S. Wyost and Jubbonti launch as first denosumab biosimilars in the US. The Center for Biosimilars. June 2, 2025. Accessed September 2, 2025. https://www.centerforbiosimilars.com/view/wyost-and-jubbonti-launch-as-first-denosumab-biosimilars-in-the-us

4. Jeremias S. Two more pairs of denosumab biosimilars enter US market. The Center for Biosimilars. July 9, 2025. Accessed September 2, 2025. https://www.centerforbiosimilars.com/view/two-more-pairs-of-denosumab-biosimilars-enter-us-market

5. Santoro C. FDA approves another pair of denosumab biosimilars, Conexxence and Bomyntra. The Center for Biosimilars. March 27, 2025. Accessed September 2, 2025. https://www.centerforbiosimilars.com/view/fda-approves-another-pair-of-denosumab-biosimilars-conexxence-and-bomyntra