Samsung Bioepis Co., Ltd. announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for two denosumab biosimilars – OBODENCE™ (60 mg pre-filled syringe) referencing Prolia (denosumab) and XBRYK™ (120mg vial) referencing Xgeva (denosumab), also known as SB16.
Recommended Indications
OBODENCE has been recommended for approval for the treatment of osteoporosis in postmenopausal women and in men at increased risk of fractures, treatment of bone loss associated with hormone ablation in men with prostate cancer at increased risk of fractures, and treatment of bone loss associated with long-term systemic glucocorticoid therapy in adult patients at increased risk of fracture.
XBRYK has been recommended for approval for the prevention of skeletal related events (pathological fracture, radiation to bone, spinal cord compression or surgery to bone) in adults with advanced malignancies involving bone, and treatment of adults and skeletally mature adolescents with giant cell tumour of bone that is unresectable or where surgical resection is likely to result in severe morbidity.
Clinical Significance
Byoungin Jung, Vice President and Regulatory Affairs Team Leader at Samsung Bioepis, stated, “In Europe alone, approximately 22.1% of women and 6.6% of men are affected by osteoporosis. Osteoporosis and cancer-related bone loss can lead to skeletal fractures, seriously affecting the quality of life of patients. Enhancing access to treatment options is essential for improving both patient outcomes and quality of life (QoL) as it allows timely treatment for patients.” He added, “If approved, OBODENCE/XBRYK would become our first endocrinology biosimilar, adding to our growing portfolio of biosimilar products that are helping to improve patient’s quality of life and access to treatments, and relieve the financial burden of healthcare systems.”
Clinical Trial Data
The CHMP’s positive opinion was based on a totality of evidence including analytical, non-clinical data, and clinical data. A randomized, double-blind, three-arm, parallel group, single-dose Phase 1 study demonstrated the pharmacokinetic (PK) equivalence between SB16, EU-sourced denosumab (EU-DEN), and US-sourced denosumab (US-DEN) in healthy male participants. The primary PK endpoints were met, in terms of area under the concentration-time curve (AUC) from time zero to infinity, and maximum serum concentration.
Additionally, a randomized, double-blind, multi-center Phase 3 study demonstrated equivalent efficacy and comparable safety, immunogenicity, PK, and pharmacodynamics (PD) profiles between SB16 and reference denosumab (DEN) in postmenopausal osteoporosis (PMO) patients. The primary endpoint was met in terms of percent (%) change from baseline in lumbar spine bone mineral density (BMD) at Month 12, and a follow-up up to Month 18 demonstrated switching to SB16 from DEN were comparable up to Month 18 in terms of efficacy, PK, PD, safety and immunogenicity.
Study Details
The Phase 1 study involved 168 healthy male participants randomized 1:1:1 to receive a single 60 mg dose of either SB16, EU-DEN, or US-DEN subcutaneously. Equivalence was determined if 90% CIs for the ratio of geometric LSMeans of the treatment groups compared were within the equivalence margin of 0.80 to 1.25.
The Phase 3 study included 457 PMO patients randomized 1:1 to receive either 60 mg of SB16 or DEN subcutaneously at Month 0, Month 6, and Month 12. At Month 12, patients in the DEN group were re-randomized 1:1 to switch to SB16 or maintain DEN. Equivalence between SB16 and DEN was declared if the 95% CI (per-protocol set) and 90% CI (full-analysis set) of LSMeans difference of % change in lumbar spine BMD at Month 12 were within the pre-defined equivalence margin.
