For US healthcare professionals only

STOBOCLO: Biosimilarity supported by a large clinical trial1

STOBOCLO was compared with Prolia® (denosumab) in a large switch trial of postmenopausal women with osteoporosis1

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 STOBOCLO or Prolia1
  • Treatment period 2 (week 52 to week 78): Patients re-randomized to continue STOBOCLO, continue Prolia, or switch to STOBOCLO1

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

STOBOCLO strengthened bones over 78 weeks—similar to Prolia1

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

Percent change from baseline in lumbar spine BMD1

  • Percent change from baseline in lumbar spine BMD by DXA at week 52 was assessed as the primary endpoint1

STOBOCLO is also approved for men with osteoporosis at high risk for fracture, and to2:

  • Treat glucocorticoid-induced osteoporosis in men and women at high risk for fracture
  • Increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer
  • Increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer

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

STOBOCLO hip BMD data reinforce equivalence to Prolia1

STOBOCLO delivered an increase in total hip BMD at 78 weeks—similar to Prolia1

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

Percent change from baseline in total hip BMD1

  • Percent change from baseline in total hip BMD at 78 weeks was assessed as a secondary endpoint

BMD, bone mineral density.

STOBOCLO and Prolia delivered similar increases in femoral neck BMD over the course of the study1

STOBOCLO increase in BMD was similar to that seen in patients taking Prolia at all time points1

Percent change from baseline in femoral neck BMD1

  • Percent change from baseline in femoral neck BMD was assessed as a secondary endpoint

Similar fracture incidence1

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

BMD, bone mineral density.

STOBOCLO delivered similar drug exposure to Prolia1

STOBOCLO and Prolia serum concentrations remained comparable throughout the trial1

Serum concentrations (ng/mL) during treatment periods 1 and 23

  • 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 displayed3

PK, pharmacokinetics; SD, standard deviation.

STOBOCLO immune profile was consistent with the Prolia profile1,3

STOBOCLO and Prolia ADA profiles were similar at week 52—even in the switch population at week 781,3

Patients ADA+ at week 781,3

  • Immunogenicity was assessed as a secondary endpoint
  • Similar trends were observed across groups in treatment periods 1 and 2

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

No changes in ADA frequency were observed after switching from Prolia to STOBOCLO1,3

STOBOCLO safety profile is similar to Prolia1

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 STOBOCLO maintenance group that 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 STOBOCLO group (11.7%)
    • 26 patients in the Prolia group (10.9%)

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

  • The most frequent TEAE reported in both groups in treatment period 2 was upper respiratory tract infection3:
    • 13 patients in the STOBOCLO maintenance group (5.9%)
    • 4 patients in the Prolia maintenance group (4.0%)
    • 11 patients in the switched to STOBOCLO group (10.9%)

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

STOBOCLO and Prolia demonstrated similar safety profiles1

TEAEs in ≥3% of patients in any treatment group3

Started
Continued
Switched To
  • Safety was assessed as a secondary endpoint1
  • During treatment period 1, similar proportions of patients in the STOBOCLO group (75.7%) and the Prolia group (70.2%) experienced TEAEs of any intensity1
  • During treatment period 2, incidence of TEAEs was also similar between patients continuing STOBOCLO (50.9%), patients continuing Prolia (42.0%), and patients switching to STOBOCLO (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, active-controlled, phase 3 trial in postmenopausal women with osteoporosis. Osteoporos Int. 2024;35(11):1919-1930. 2. STOBOCLO Prescribing Information. Celltrion USA, Inc; 2024. 3. 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

WARNING: SEVERE HYPOCALCEMIA IN PATIENTS WITH ADVANCED KIDNEY DISEASE

Patients with advanced chronic kidney disease (eGFR < 30 mL/min/1.73 m2), including dialysis-dependent patients, are at greater risk of severe hypocalcemia following the administration of denosumab products. Severe hypocalcemia resulting in hospitalization, life-threatening events and fatal cases have been reported

The presence of chronic kidney disease-mineral bone disorder (CKD-MBD) markedly increases the risk of hypocalcemia in these patients.

Prior to initiating STOBOCLO in patients with advanced chronic kidney disease, evaluate for the presence of CKD-MBD. Treatment with STOBOCLO in these patients should be supervised by a healthcare provider with expertise in the diagnosis and management of CKD-MBD

Contraindications:

  • Hypocalcemia: Pre-existing hypocalcemia must be corrected before initiating therapy.
  • Pregnancy: Denosumab products may cause fetal harm when administered to a pregnant woman.
  • Hypersensitivity: Known hypersensitivity to denosumab products.

Severe Hypocalcemia and Mineral Metabolism Changes. Severe hypocalcemia can occur. Ensure adequate calcium and vitamin D supplementation.

Drug Products with Same Active Ingredient. Patients receiving STOBOCLO 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 STOBOCLO.

Osteonecrosis of the Jaw (ONJ). ONJ can occur in patients on STOBOCLO, particularly after tooth extraction and/or local infection with delayed healing. A routine oral exam is recommended before starting STOBOCLO, with a dental evaluation and preventive care for high-risk patients. Good oral hygiene should be maintained, and ONJ-risk drugs may heighten ONJ likelihood, especially with extended STOBOCLO exposure. For invasive dental procedures, individualize treatment based on clinical judgment. If ONJ develops, consult a dentist or oral surgeon. Extensive surgery may worsen ONJ, consider discontinuing STOBOCLO based on a benefit-risk assessment.

Atypical Subtrochanteric and Diaphyseal Femoral Fractures. Atypical low energy or low trauma fractures of the shaft have been reported in patients receiving denosumab products. During STOBOCLO 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 STOBOCLO therapy should be considered, pending a benefit-risk assessment, on an individual basis.

Multiple Vertebral Fractures (MVF) Following Discontinuation of Treatment. Following discontinuation of denosumab treatment, fracture risk increases, including the risk of multiple vertebral fractures. Prior vertebral fracture was a predictor of multiple vertebral fractures after denosumab discontinuation. Evaluate an individual's benefit-risk before initiating treatment with STOBOCLO. If STOBOCLO treatment is discontinued, patients should be transitioned to an alternative antiresorptive therapy.

Serious Infections. In a trial of women with postmenopausal osteoporosis, serious infections were more frequent with denosumab than placebo, including skin, abdominal, urinary, ear infections, and endocarditis. Overall infection rates were similar between groups. Advise patients to seek medical attention for severe infection symptoms like cellulitis. Those on immunosuppressants or with weakened immune systems may face higher risks. Assess the benefit-risk profile before starting STOBOCLO, and reconsider its use if serious infections develop.

Dermatologic Adverse Reactions. Epidermal and dermal adverse events such as dermatitis, eczema, and rashes have been reported in patients treated with denosumab. Consider discontinuing STOBOCLO if severe symptoms develop.

Musculoskeletal Pain. In postmarketing experience, severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported in patients taking denosumab products. Consider discontinuing use if severe symptoms develop.

Suppression of Bone Turnover. In clinical trials in women with postmenopausal osteoporosis, denosumab significantly suppressed bone remodeling, with unknown long-term effects that may lead to osteonecrosis of the jaw, atypical fractures, or delayed fracture healing; patients should be monitored for these outcomes.

Hypercalcemia in Pediatric Patients with Osteogenesis Imperfecta. STOBOCLO is not indicated for use in pediatric patients. Hypercalcemia has been reported in pediatric patients with osteogenesis imperfecta treated with denosumab products. Some cases required hospitalization.

Adverse Reactions:

  • Postmenopausal osteoporosis: Most common adverse reactions (> 5%) were: back pain, pain in extremity, hypercholesterolemia, musculoskeletal pain, and cystitis. Pancreatitis has been reported in clinical trials.
  • Male osteoporosis: Most common adverse reactions (> 5%) were: back pain, arthralgia, and nasopharyngitis.
  • Glucocorticoid-induced osteoporosis: Most common adverse reactions (> 3%) were: back pain, hypertension, bronchitis, and headache.
  • Bone loss due to hormone ablation for cancer: Most common adverse reactions (≥10%) were: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials.

Please see full Prescribing Information, including BOXED WARNING.

INDICATIONS

STOBOCLO (denosumab-bmwo) is a RANK ligand (RANKL) inhibitor 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 or in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer
  • of glucocorticoid-induced osteoporosis in men and women at high risk for fracture
  • to increase bone mass in women at high risk for fracture receiving an adjuvant aromatase inhibitor therapy for breast cancer

INDICATIONS

STOBOCLO (denosumab-bmwo) is a RANK ligand (RANKL) inhibitor 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 or in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer
  • of glucocorticoid-induced osteoporosis in men and women at high risk for fracture
  • to increase bone mass in women at high risk for fracture receiving an adjuvant aromatase inhibitor therapy for breast cancer;

IMPORTANT SAFETY INFORMATION

WARNING: SEVERE HYPOCALCEMIA IN PATIENTS WITH ADVANCED KIDNEY DISEASE

Patients with advanced chronic kidney disease (eGFR < 30 mL/min/1.73 m2), including dialysis-dependent patients, are at greater risk of severe hypocalcemia following the administration of denosumab products. Severe hypocalcemia resulting in hospitalization, life-threatening events and fatal cases have been reported

The presence of chronic kidney disease-mineral bone disorder (CKD-MBD) markedly increases the risk of hypocalcemia in these patients.

Prior to initiating STOBOCLO in patients with advanced chronic kidney disease, evaluate for the presence of CKD-MBD. Treatment with STOBOCLO in these patients should be supervised by a healthcare provider with expertise in the diagnosis and management of CKD-MBD

Contraindications:

  • Hypocalcemia: Pre-existing hypocalcemia must be corrected before initiating therapy.
  • Pregnancy: Denosumab products may cause fetal harm when administered to a pregnant woman.
  • Hypersensitivity: Known hypersensitivity to denosumab products.

Severe Hypocalcemia and Mineral Metabolism Changes. Severe hypocalcemia can occur. Ensure adequate calcium and vitamin D supplementation.

Drug Products with Same Active Ingredient. Patients receiving STOBOCLO 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 STOBOCLO.

Osteonecrosis of the Jaw (ONJ). ONJ can occur in patients on STOBOCLO, particularly after tooth extraction and/or local infection with delayed healing. A routine oral exam is recommended before starting STOBOCLO, with a dental evaluation and preventive care for high-risk patients. Good oral hygiene should be maintained, and ONJ-risk drugs may heighten ONJ likelihood, especially with extended STOBOCLO exposure. For invasive dental procedures, individualize treatment based on clinical judgment. If ONJ develops, consult a dentist or oral surgeon. Extensive surgery may worsen ONJ, consider discontinuing STOBOCLO based on a benefit-risk assessment.

Atypical Subtrochanteric and Diaphyseal Femoral Fractures. Atypical low energy or low trauma fractures of the shaft have been reported in patients receiving denosumab products. During STOBOCLO 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 STOBOCLO therapy should be considered, pending a benefit-risk assessment, on an individual basis.

Multiple Vertebral Fractures (MVF) Following Discontinuation of Treatment. Following discontinuation of denosumab treatment, fracture risk increases, including the risk of multiple vertebral fractures. Prior vertebral fracture was a predictor of multiple vertebral fractures after denosumab discontinuation. Evaluate an individual's benefit-risk before initiating treatment with STOBOCLO. If STOBOCLO treatment is discontinued, patients should be transitioned to an alternative antiresorptive therapy.

Serious Infections. In a trial of women with postmenopausal osteoporosis, serious infections were more frequent with denosumab than placebo, including skin, abdominal, urinary, ear infections, and endocarditis. Overall infection rates were similar between groups. Advise patients to seek medical attention for severe infection symptoms like cellulitis. Those on immunosuppressants or with weakened immune systems may face higher risks. Assess the benefit-risk profile before starting STOBOCLO, and reconsider its use if serious infections develop.

Dermatologic Adverse Reactions. Epidermal and dermal adverse events such as dermatitis, eczema, and rashes have been reported in patients treated with denosumab. Consider discontinuing STOBOCLO if severe symptoms develop.

Musculoskeletal Pain. In postmarketing experience, severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported in patients taking denosumab products. Consider discontinuing use if severe symptoms develop.

Suppression of Bone Turnover. In clinical trials in women with postmenopausal osteoporosis, denosumab significantly suppressed bone remodeling, with unknown long-term effects that may lead to osteonecrosis of the jaw, atypical fractures, or delayed fracture healing; patients should be monitored for these outcomes.

Hypercalcemia in Pediatric Patients with Osteogenesis Imperfecta. STOBOCLO is not indicated for use in pediatric patients. Hypercalcemia has been reported in pediatric patients with osteogenesis imperfecta treated with denosumab products. Some cases required hospitalization.

Adverse Reactions:

  • Postmenopausal osteoporosis: Most common adverse reactions (> 5%) were: back pain, pain in extremity, hypercholesterolemia, musculoskeletal pain, and cystitis. Pancreatitis has been reported in clinical trials.
  • Male osteoporosis: Most common adverse reactions (> 5%) were: back pain, arthralgia, and nasopharyngitis.
  • Glucocorticoid-induced osteoporosis: Most common adverse reactions (> 3%) were: back pain, hypertension, bronchitis, and headache.
  • Bone loss due to hormone ablation for cancer: Most common adverse reactions (≥10%) were: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials.

Please see full Prescribing Information, including BOXED WARNING.

INDICATIONS

STOBOCLO (denosumab-bmwo) is a RANK ligand (RANKL) inhibitor 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 or in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer
  • of glucocorticoid-induced osteoporosis in men and women at high risk for fracture
  • to increase bone mass in women at high risk for fracture receiving an adjuvant aromatase inhibitor therapy for breast cancer