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Denosumab Biosimilar Earns European Approval in Advanced Malignancies Involving the Bone and Giant Cell Tumors of the Bone

Denbrayce was approved in Europe for the treatment of skeletal-related events in advanced malignancies involving the bone and giant cell tumor of the bone.

Denosumab Biosimilars |  Image Credit: © barinovalena  - stock.adobe.com

Denosumab Biosimilars |
Image Credit: © barinovalena
- stock.adobe.com

The European Commission (EC) has approved the denosumab (Xgeva) biosimilar Denbrayce for the prevention of skeletal-related events in adult patients with advanced malignancies involving the bone and in adult and skeletally mature adolescent patients with giant cell tumor of the bone.1 This regulatory decision follows a positive recommendation from the Committee for Medicinal Products for Human Use.

Denosumab is a humanized monoclonal antibody that inhibits the receptor activator of nuclear factor kappa-B ligand. This inhibition prevents the development of osteoclasts, which are responsible for bone breakdown.

“This approval is a testament to mAbxience’s dedication to scientific excellence and our commitment to broadening access to essential biologic therapies,” Jurgen Van Broeck, chief executive officer of mAbxience, stated in a news release. “We are proud to contribute to reducing the burden of osteoporosis, cancer-related bone conditions, and rare bone diseases in Europe. This milestone brings us one step closer to ensuring that more patients across Europe can benefit from high-quality, affordable treatment options.”

Notably,in March 2025, the FDA approved the biosimilars denosumab-bmwo (Stobloco) and (Osenvelt), which are biosimilars referencing Prolia and Xgeva, respectively, for all indications of their reference products, which include the increase of bone mass in men at high risk for fracture who are receiving androgen deprivation therapy for nonmetastatic prostate cancer, the increase of bone mass in women at high risk for fracture who are receiving an adjuvant aromatase inhibitor therapy for breast cancer, the prevention of skeletal-related events in patients with multiple myeloma and those with bone metastases from solid tumors, and to treat adult and skeletally mature adolescent patients with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity.2 These approvals were supported in part by data from a phase 3 study (NCT04757376), which compared the efficacy, pharmacodynamics, pharmacokinetics, safety, and immunogenicity of denosumab-bmwo vs reference denosumab in postmenopausal women with osteoporosis.

Data from the trial revealed that denosumab-bmwo produced a least squares (LS) mean difference in terms of lumbar spine bone mineral density percentage change from baseline to week 52 of –0.139% (95% CI, –0.826% to 0.548%) in the full analysis set.3 This figure was –0.280% (95% CI, –0.973% to 0.414%) in the per-protocol set. Both findings were within the predefined equivalence margin.

Additionally, the geometric LS mean ratio for serum carboxy-terminal cross-linking telopeptide of type I collagen through week 26 was 94.94% (95% CI, 90.75%-99.32%). This finding met the predefined 80% to 125% equivalence criteria.

The double-blind, active-controlled study enrolled 479 postmenopausal women with osteoporosis. To be eligible for the study, patients needed to be between 50 and 80 years of age, have at least 3 evaluable vertebrae in the lumbar spine, have a lumbar spine BMD T-score of at least –2.5 up to and including –4.0 at screening, have at least 1 evaluable hip at screening, and have good general health. Patients were excluded if they had received prior treatment with reference or biosimilar denosumab or other biologics for osteoporosis, intravenous bisphosphonates, fluoride, or strontium for osteoporosis within the past 5 years prior to first administration of study drug; had received oral bisphosphonates at least 3 years cumulatively prior to screening; or had received any dose of oral bisphosphonates within 12 months prior to screening.

Patients were randomly assigned 1:1 to receive denosumab-bmwo or denosumab. Both agents were administered at a dose of 60 mg subcutaneously. The agents were given at weeks 0, 26, and 52. The primary efficacy end points were the percent change from baseline in lumbar spine bone mineral density at week 52 and pharmacodynamics through the first 26 weeks. Investigators also evaluated secondary efficacy, pharmacodynamic, pharmacokinetic, safety, and immunogenicity end points.

The study included an initial 28-day screening period (days –28 to –1), treatment period 1 (week 0 [day 1] to week 52), treatment period 2 (weeks 52 to 78), and an end-of-study visit at week 78. Prior to treatment period 2, patients underwent a second random assignment to maintain blinding.

In the news release, mAbxience noted that the denosumab biosimilar Izamby, which references Prolia, was also approved by the EC.1 The biosimilar is indicated for the treatment of osteoporosis in postmenopausal women and in men at increased risk of fractures.

References

  1. mAbxience announces European Commission approval of denosumab biosimilars. News release. mAbxience. July 2, 2025. Accessed July 2, 2025. https://mabxience.com/mabxience-announces-european-commission-approval-of-denosumab-biosimilars/
  2. Celltrion receives U.S. FDA approval for Stoboclo (denosumab-bmwo) and Osenvelt (denosumab-bmwo) biosimilars referencing Prolia and Xgeva. Celltrion. March 4, 2025. Accessed July 2, 2025. https://www.celltrion.com/en-us/company/media-center/press-release/3768
  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. Osteoporosis international. 2024;35(11):1919-1930. doi:10.1007/s00198-024-07161-x

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