For US healthcare professionals only

Denosumab-bmwo: Studied in a large phase 3 clinical study1

Denosumab-bmwo and reference denosumab patients continued therapy for 78 weeks1


Inclusion criteria: Postmenopausal women aged 50 to 80 years inclusive with ≥3 evaluable lumbar vertebrae with a bone mineral density T-score of ≤-2.5 and ≥-4.0 at screening and at least 1 evaluable hip at baseline.1

  • Primary endpoint: Percent change from baseline in lumbar spine BMD by DXA at week 521
  • Additional endpoints: Percent change from baseline in lumbar spine, total hip, and femoral neck BMD at weeks 26, 52, and 78; and incidence of new fractures (vertebral, nonvertebral, hip)1
  • Treatment period 1 (week 0 to week 52): Patients were randomized 1:1 to receive either denosumab-bmwo or reference denosumab1
  • Treatment period 2 (week 52 to week 78): Patients re-randomized to continue denosumab-bmwo, continue reference denosumab, or switch to denosumab-bmwo1

BMD, bone mineral density; DXA, dual-energy X-ray absorptiometry.

Denosumab-bmwo strengthened bones over 78 weeks—similar to reference denosumab1

All treatment groups demonstrated significant change over baseline at the end of the trial1

Percent change from baseline in lumbar spine BMD over 78 weeks1


  • Percent change from baseline in lumbar spine BMD was assessed as the primary endpoint1

Based partly on the findings of this study in postmenopausal women with osteoporosis (treated with denosumab), denosumab-bmwo has been approved as biosimilar to Xgeva across all Xgeva indications, including2:

  • Prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors
  • 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
  • Treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy

The FDA looks at a wide variety of tests and data to determine that a drug is biosimilar to a reference product, including clinical trials, blood and immune system evaluations, and chemical analyses. Denosumab-bmwo passed these tests and is officially biosimilar to Xgeva.2-4

Denosumab-bmwo and reference denosumab delivered similar increases in total hip BMD at 78 weeks1

All treatment groups saw a significant increase in total hip BMD by end of study1

Percent change from baseline in total hip BMD at 26, 52, and 78 weeks1


  • Percent change from baseline in total hip BMD was assessed as a secondary endpoint1

BMD, bone mineral density.

Denosumab-bmwo and reference denosumab delivered similar increases in femoral neck BMD over the course of the study1

Denosumab-bmwo increase in BMD was similar to that seen in patients taking reference denosumab at all time points1

Percent change from baseline in femoral neck BMD1


Other key secondary endpoints:

Similar fracture incidence1

  • New vertebral fractures occurred in 0.4% of patients in both the denosumab-bmwo and reference denosumab groups by week 52
  • Nonvertebral fractures were reported in 0.8% of patients in the denosumab-bmwo group and 1.7% of patients in the reference denosumab group by week 52
  • No hip fractures were reported in either group

BMD, bone mineral density.

Denosumab-bmwo delivered similar drug exposure to reference denosumab1

Denosumab-bmwo and reference denosumab serum concentrations remained comparable throughout the trial1

Serum concentrations (ng/mL) during treatment periods 1 and 25


  • PK data were assessed as a secondary endpoint1
  • Serum concentrations below the lower limit of quantification were set to zero, and only positive mean ±SD values were displayed5

PK, pharmacokinetics; SD, standard deviation.

Denosumab-bmwo and reference denosumab showed similar immune profiles1,5

Denosumab-bmwo and reference denosumab ADA profiles were similar across all treatment groups1,5

Patients ADA+ at week 781,5

ADA, antidrug antibody; ADA+, antidrug antibody positive.

Denosumab-bmwo has a safety profile similar to reference denosumab1

Denosumab-bmwo is generally well tolerated, with a comparable safety profile to reference denosumab1

TEAEs: Patients with at least one adverse event related to study drug1


  • Safety was assessed as a secondary endpoint1
  • There was one death due to a TEAE of “genital neoplasm malignant female” in the denosumab-bmwo maintenance group which was not considered related to the study drug by the investigator1
  • The most frequent TEAE reported in both groups in treatment period 1 was COVID-191:
    • 28 patients in the denosumab-bmwo group (11.7%)
    • 26 patients in the reference denosumab group (10.9%)
  • The most frequent TEAE reported in both groups in treatment period 2 was upper respiratory tract infection5:
    • 13 patients in the denosumab-bmwo maintenance group (5.9%)
    • 4 patients in the reference denosumab maintenance group (4.0%)
    • 11 patients in the switched to denosumab-bmwo group (10.9%)

TESAEs: Patients with at least one serious adverse event related to study drug1


TEAE, treatment-emergent adverse event; TESAE, treatment-emergent serious adverse event.

Denosumab-bmwo and reference denosumab demonstrated similar safety profiles1

TEAEs in ≥3% of patients in any treatment group5

Started
Continued
Switched To

  • Safety was assessed as a secondary endpoint1
  • During treatment period 1, similar proportions of patients in the denosumab-bmwo group (75.7%) and the denosumab group (70.2%) experienced TEAEs of any intensity1
  • During treatment period 2, incidence of TEAEs was also similar between patients continuing denosumab-bmwo (50.9%), patients continuing reference denosumab (42.0%) and patients switching to denosumab-bmwo (56.4%)1

TEAEs, treatment-emergent adverse events.

References: 1. Reginster JY, Czerwinski E, Wilk K, et al. Efficacy and safety of candidate biosimilar CT-P41 versus reference denosumab: a double-blind, randomized, activecontrolled, phase 3 trial in postmenopausal women with osteoporosis. Osteoporos Int. 2024;35(11):1919-1930. 2. OSENVELT Prescribing Information. Celltrion, USA, Inc.; 2024. 3. Xgeva Prescribing Information. Amgen, Inc; 2020. 4. US Food and Drug Administration. Biosimilar Product Regulatory Review and Approval. Accessed March 17, 2025. https://www.fda.gov/files/drugs/published/Biosimilar-Product-Regulatory-Review-and-Approval.pdf 5. Reginster JY, Czerwinski E, Wilk K, et al. Efficacy and safety of candidate biosimilar CT-P41 versus reference denosumab: a double-blind, randomized, active controlled, phase 3 trial in postmenopausal women with osteoporosis. Supplement. Osteoporos Int. doi:10.1007/s00198-024-07161-x

IMPORTANT SAFETY INFORMATION

Contraindications: Patients with hypocalcemia or with known clinically significant hypersensitivity to denosumab products.

Drug Products with Same Active Ingredient. Patients receiving OSENVELT should not receive other denosumab products concomitantly.

Hypersensitivity. Clinically significant hypersensitivity including anaphylaxis has been reported with denosumab products. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue further use of OSENVELT.

Hypocalcemia. Severe hypocalcemia can occur, and fatal cases have been reported. Monitor calcium levels and calcium and vitamin D intake.

Osteonecrosis of the Jaw (ONJ). ONJ can occur in patients on OSENVELT. A routine oral exam and appropriate preventive dentistry are recommended before starting and during treatment with OSENVELT. Good oral hygiene should be maintained. Avoid invasive dental procedures during treatment with OSENVELT. For invasive dental procedures, consider temporary discontinuation of OSENVELT. If ONJ develops, consult a dentist or oral surgeon. Extensive surgery may worsen ONJ, consider discontinuing OSENVELT based on a benefit-risk assessment.

Atypical Subtrochanteric and Diaphyseal Femoral Fractures. Atypical femoral fracture has been reported with denosumab products. During OSENVELT treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Patients with thigh or groin pain should be evaluated for an atypical femur fracture, including assessment for potential fractures in the contralateral limb. Interruption of OSENVELT therapy should be considered, pending a benefit-risk assessment, on an individual basis.

Hypercalcemia Following Treatment Discontinuation in Patients with Giant Cell Tumor of Bone and in Patients with Growing Skeletons. Clinically significant hypercalcemia, sometimes requiring hospitalization and complicated by acute renal injury, has occurred in denosumab-treated patients with giant cell tumor of bone and in those with growing skeletons, often within the first year after discontinuation. After treatment discontinuation, monitor for hypercalcemia symptoms, check serum calcium periodically, reassess calcium and vitamin D needs, and manage as appropriate.

Multiple Vertebral Fractures (MVF) Following Treatment Discontinuation. Following discontinuation of denosumab treatment, fracture risk increases, including the risk of multiple vertebral fractures. Evaluate the individual patient’s risk for vertebral fractures after OSENVELT discontinuation.

Embryo-Fetal Toxicity. Denosumab may cause fetal harm based on animal studies and its mechanism of action. Verify pregnancy status in females of reproductive potential before starting OSENVELT and advise them to use effective contraception during treatment and for 5 months after the last dose to prevent fetal harm.

Adverse Reactions:

  • Bone Metastasis from Solid Tumors: Most common adverse reactions (≥25%) were fatigue/asthenia, hypophosphatemia, and nausea.
  • Multiple Myeloma: Most common adverse reactions (≥10%) were diarrhea, nausea, anemia, back pain, thrombocytopenia, peripheral edema, hypocalcemia, upper respiratory tract infection, rash, and headache.
  • Giant Cell Tumor of Bone: Most common adverse reactions (≥10%) were arthralgia, headache, nausea, back pain, fatigue, and pain in extremity.
  • Hypercalcemia of Malignancy: Most common adverse reactions (>20%) were nausea, dyspnea, decreased appetite, headache, peripheral edema, vomiting, anemia, constipation, and diarrhea.

Please see full Prescribing Information.

INDICATIONS

OSENVELT® (denosumab-bmwo) is a RANK ligand (RANKL) inhibitor indicated for:

  • Prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors.
  • 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.
  • Treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy.

INDICATIONS

OSENVELT® (denosumab-bmwo) is a RANK ligand (RANKL) inhibitor indicated for:

  • Prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors.
  • 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.
  • Treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy.

IMPORTANT SAFETY INFORMATION

Contraindications: Patients with hypocalcemia or with known clinically significant hypersensitivity to denosumab products.

Drug Products with Same Active Ingredient. Patients receiving OSENVELT should not receive other denosumab products concomitantly.

Hypersensitivity. Clinically significant hypersensitivity including anaphylaxis has been reported with denosumab products. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue further use of OSENVELT.

Hypocalcemia. Severe hypocalcemia can occur, and fatal cases have been reported. Monitor calcium levels and calcium and vitamin D intake.

Osteonecrosis of the Jaw (ONJ). ONJ can occur in patients on OSENVELT. A routine oral exam and appropriate preventive dentistry are recommended before starting and during treatment with OSENVELT. Good oral hygiene should be maintained. Avoid invasive dental procedures during treatment with OSENVELT. For invasive dental procedures, consider temporary discontinuation of OSENVELT. If ONJ develops, consult a dentist or oral surgeon. Extensive surgery may worsen ONJ, consider discontinuing OSENVELT based on a benefit-risk assessment.

Atypical Subtrochanteric and Diaphyseal Femoral Fractures. Atypical femoral fracture has been reported with denosumab products. During OSENVELT treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Patients with thigh or groin pain should be evaluated for an atypical femur fracture, including assessment for potential fractures in the contralateral limb. Interruption of OSENVELT therapy should be considered, pending a benefit-risk assessment, on an individual basis.

Hypercalcemia Following Treatment Discontinuation in Patients with Giant Cell Tumor of Bone and in Patients with Growing Skeletons. Clinically significant hypercalcemia, sometimes requiring hospitalization and complicated by acute renal injury, has occurred in denosumab-treated patients with giant cell tumor of bone and in those with growing skeletons, often within the first year after discontinuation. After treatment discontinuation, monitor for hypercalcemia symptoms, check serum calcium periodically, reassess calcium and vitamin D needs, and manage as appropriate.

Multiple Vertebral Fractures (MVF) Following Treatment Discontinuation. Following discontinuation of denosumab treatment, fracture risk increases, including the risk of multiple vertebral fractures. Evaluate the individual patient’s risk for vertebral fractures after OSENVELT discontinuation.

Embryo-Fetal Toxicity. Denosumab may cause fetal harm based on animal studies and its mechanism of action. Verify pregnancy status in females of reproductive potential before starting OSENVELT and advise them to use effective contraception during treatment and for 5 months after the last dose to prevent fetal harm.

Adverse Reactions:

  • Bone Metastasis from Solid Tumors: Most common adverse reactions (≥25%) were fatigue/asthenia, hypophosphatemia, and nausea.
  • Multiple Myeloma: Most common adverse reactions (≥10%) were diarrhea, nausea, anemia, back pain, thrombocytopenia, peripheral edema, hypocalcemia, upper respiratory tract infection, rash, and headache.
  • Giant Cell Tumor of Bone: Most common adverse reactions (≥10%) were arthralgia, headache, nausea, back pain, fatigue, and pain in extremity.
  • Hypercalcemia of Malignancy: Most common adverse reactions (>20%) were nausea, dyspnea, decreased appetite, headache, peripheral edema, vomiting, anemia, constipation, and diarrhea.

Please see full Prescribing Information.

INDICATIONS

OSENVELT® (denosumab-bmwo) is a RANK ligand (RANKL) inhibitor indicated for:

  • Prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors.
  • 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.
  • Treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy.