FDA Grants Interchangeability Designation to 2 Denosumab Biosimilars

The FDA has approved 2 denosumab biosimilars—Stoboclo (denosumab-bmwo) and Osenvelt (denosumab-bmwo)—as interchangeable with the 2 reference products—Prolia (denosumab) and Xgeva (denosumab), respectively—for all approved indications, according to a press release from the developer, Celltrion, Inc.¹ As of October 29, 2025, the interchangeability designation has been effective.

The designation was supported by comprehensive evidence, including results from a phase 3 trial (NCT04757376) in postmenopausal women with osteoporosis, which was designed to evaluate the efficacy, safety, pharmacodynamics, pharmacokinetics, and immunogenicity of the denosumab biosimilars compared with their reference products.

Recent FDA draft guidance stated that biosimilar applicants could request an interchangeability designation using data included in their biologics license application; in the past, this designation was only granted to biosimilars that submitted multiple switch studies and met additional data criteria.

Previously, in March 2025, the FDA approved both Stoboclo and Osenvelt for all indications of the previously referenced Prolia and Xgeva.² In July 2025, the new indications of denosumab-bmwo became commercially available in the US as treatment for select patient groups with osteoporosis, multiple myeloma, and solid tumors with bone metastases.³

"Today's [interchangeability designations reinforce confidence in Stoboclo and Osenvelt among physicians and pharmacists, facilitating a more seamless switch from the reference products to our denosumab biosimilars," stated Thomas Nusbickel, chief commercial officer at Celltrion USA, in the press release. "Building on our strong heritage in biosimilars, Celltrion remains committed to offering more affordable and much-needed treatment options to patients living with skeletal diseases, creating greater potential to deliver savings to patients and the US health care system."

Stoboclo

Stoboclo, a RANK ligand (RANKL) inhibitor referencing Prolia, was introduced in the US market in July 2025 and is currently available in a 60 mg/mL injection. It is indicated for the treatment of:

• Postmenopausal women with osteoporosis who are at high risk for fracture
• Men with osteoporosis who are at high risk for fracture, or in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer
• Men and women at high risk for fracture with glucocorticoid-induced osteoporosis
• Women at high risk for fracture receiving an adjuvant aromatase inhibitor for breast cancer

The label notes that Stoboclo is contraindicated in hypocalcemia, pregnant women, and patients with known hypersensitivity to denosumab.

The most common adverse reactions with Stoboclo were back pain, pain in extremity, hypercholesterolemia, musculoskeletal pain, and cystitis, with pancreatitis reported in clinical trials, for postmenopausal women with osteoporosis; back pain, arthralgia, and nasopharyngitis for males with osteoporosis; back pain, hypertension, bronchitis, and headache for those with glucocorticoid-induced osteoporosis; and arthralgia and back pain, with pain in extremity and musculoskeletal pain reported in clinical trials, for those with bone loss due to hormone ablation for cancer.

There is also a Risk Evaluation and Mitigation Strategy (REMS) program in place to inform healthcare providers and patients about the serious risk of severe hypocalcemia in patients with advanced kidney disease.

Osenvelt

Osenvelt, a RANKL inhibitor referencing Xgeva, was introduced into the US market in July 2025 as a 120 mg/1.7 mL injection. It is indicated for the treatment of:

• Patients with multiple myeloma and patients with bone metastases from solid tumors are treated to prevent skeletal-related events
• 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
• Hypercalcemia of malignancy refractory to bisphosphonate therapy

The label notes that Osenvelt is contraindicated for patients with hypocalcemia or known clinically significant hypersensitivity to denosumab products.

The most common adverse reactions with Osenvelt were fatigue/asthenia, hypophosphatemia, and nausea in patients with bone metastases from solid tumors; diarrhea, nausea, anemia, back pain, thrombocytopenia, peripheral edema, and hypocalcemia in patients with multiple myeloma; arthralgia, headache, nausea, back pain, fatigue, and pain in extremity in patients with giant cell tumor of bone; and nausea, dyspnea, decreased appetite, peripheral edema, vomiting, anemia, constipation, and diarrhea in patients with hypercalcemia of malignancy.

References

1. U.S. FDA grants interchangeability designation to Celltrion’s denosumab biosimilars, STOBOCLO® (denosumab-bmwo) and OSENVELT® (denosumab-bmwo). News release. Celltrion Inc. October 30, 2025. Accessed October 30, 2025. https://tinyurl.com/5exn3z82
2. 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 October 30, 2025. https://tinyurl.com/ahnwrx57
3. Celltrion USA announces U.S. launch of denosumab biosimilars, STOBOCLO® and OSENVELT® (denosumab-bmwo). News release. Celltrion USA. July 7, 2025. Accessed October 30, 2025. https://tinyurl.com/er2pfvzn