Denosumab Biosimilars Stoboclo and Osenvelt Receive FDA Approval

On 3 March 2025, the United States Food and Drug Administration (FDA) approved Stoboclo (denosumab-bmwo, Celltrion), a biosimilar to Prolia (denosumab, Amgen), and Osenvelt(denosumab-bmwo, Celltrion), a biosimilar to Xgeva (denosumab, Amgen).

Xgeva is the form of Prolia used in cancer. Prolia contains 60 mg, whereas Xgeva contains 120 mg.

A biosimilar is a biotechnology medicine highly similar to an already approved reference biologic, although small variations may exist. It must have the same clinical efficacy, safety, and immunogenicity profile. To gain FDA approval, a biosimilar must undergo extensive comparative studies showing structural, functional, pharmacokinetic, pharmacodynamic, clinical efficacy, and safety similarity to the reference medicine . The approval process requires evidence of no clinically meaningful difference from the reference, through analytical studies, animal studies, and at least one clinical study .

What Is Prolia? Mechanism and Authorization in Türkiye

Prolia (denosumab), a monoclonal antibody that inhibits RANK Ligand (RANKL) , prevents osteoclast activation and bone breakdown, increasing bone mineral density and reducing fractures. By preventing RANKL from binding to osteoclasts, it inhibits bone resorption and is effective for osteoporosis.

It first received FDA approval on 1 June 2010 for treatment of postmenopausal women with osteoporosis at high fracture risk .

Prolia 60 mg SC injection , under its Turkish Ministry of Health authorization, may be used for the following indications:

1. Postmenopausal Osteoporosis:

   • Treatment of women and men with postmenopausal osteoporosis at high fracture risk.

2. Osteoporosis Associated With Hormone Ablation:

   • Treatment of osteoporosis in patients with nonmetastatic prostate cancer receiving hormone ablation (androgen deprivation therapy).
   • Treatment of osteoporosis in patients at high fracture risk receiving adjuvant aromatase inhibitors for breast cancer.

3. Glucocorticoid-Induced Osteoporosis:

   • Prevention and treatment of bone loss from long-term glucocorticoid therapy in adults at high fracture risk.

What Is Xgeva? Mechanism and Authorization in Türkiye

Containing the same active ingredient, Xgeva is the form used in cancer. Prolia contains 60 mg, while Xgeva contains 120 mg.

Xgeva first received FDA approval on 18 November 2010 for prevention of skeletal-related events in patients with solid tumors and bone metastases .

Xgeva 120 mg SC injection , under its Turkish Ministry of Health authorization, may be used for the following indications:

1. Bone Metastases:

   • In patients not previously treated with zoledronic acid, with metastases to weight-bearing bones such as vertebrae, femur, or humerus at high risk of fracture or compression, breast cancer, hormone-refractory prostate cancer, or non-small-cell lung cancer may be treated until bone progression.
   • Denosumab cannot be continued after bone progression or a skeletal-related event.

2. Giant Cell Tumor of Bone:

   • Treatment of adults and skeletally mature adolescents whose tumors cannot be surgically removed or whose surgery is likely to cause severe morbidity.

3. Multiple Myeloma:

   • Prevention of myeloma-related bone complications in patients with multiple myeloma requiring antimyeloma therapy and creatinine clearance below 30 ml/min (milliliters per minute).

FDA Approvals for the New Biosimilars

Stoboclo Indications

Stoboclo, a Prolia biosimilar, is approved for:

• Postmenopausal women with osteoporosis at high fracture risk,

• Men with osteoporosis at high fracture risk,

• Men and women with glucocorticoid-induced osteoporosis at high fracture risk,

• Men at high fracture risk receiving androgen deprivation for nonmetastatic prostate cancer,

• Women at high fracture risk receiving adjuvant aromatase inhibitors for breast cancer.

Osenvelt Indications

Osenvelt, an Xgeva biosimilar, is approved for:

• Prevention of skeletal-related events in patients with multiple myeloma or bone metastases from solid tumors,

• Treatment of giant cell tumor of bone in adults and skeletally mature adolescents when unresectable or when surgery is likely to cause severe morbidity,

• Treatment of hypercalcemia of malignancy refractory to bisphosphonates.

Clinical Data Supporting Approval

Approval was based on a comprehensive clinical data package, including a double-blind, randomized phase 3 trial (NCT04757376) comparing denosumab-bmwo with reference Prolia in postmenopausal women with osteoporosis.

Study Design:

• The study had two treatment periods.

• In the first, 479 patients were randomized 1:1 to denosumab-bmwo or the reference medicine.

• Patients initially receiving the biosimilar continued it at week 52. Those receiving Prolia were randomized to continue Prolia or switch to the biosimilar during the second period through week 78.

• The primary endpoint was percentage change from baseline in lumbar spine bone mineral density at week 52.

Results

Findings at week 52:

• Primary Endpoint: Percentage change from baseline in lumbar spine bone mineral density was equivalent between the biosimilar and Prolia (least-squares mean difference: full analysis set: -0.139 [95% CI, -0.826, 0.548]; per-protocol set: -0.280 [95% CI, -0.973, 0.414]).

• Findings at week 78: Efficacy remained similar after switching from the reference product to the biosimilar (secondary endpoint).

• Safety, pharmacokinetic, and immunogenicity data showed similarity between the biosimilar and reference medicine.

Following FDA approval, Stoboclo and Osenvelt are expected to reach the market in June 2025. These approvals may expand access and competition by offering new options for osteoporosis and cancer-related bone disease.