Denosumab Biosimilars Earn Positive CHMP Opinion for Bone Loss and Giant Cell Tumor of Bone

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The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for the denosumab biosimilars Obodence (as a 60-mg pre-filled syringe) and Xbryk (as a 120-mg vial) for all indications referencing Prolia and Xgeva, respectively. These biosimilars are also known as SB16.¹

Obodence is recommended for approval for the treatment of bone loss associated with hormone ablation in patients with prostate cancer at increased risk of fractures, the treatment of osteoporosis in postmenopausal women and in men, and the treatment of bone loss associated with long-term systemic glucocorticoid therapy in adult patients facing increased fracture risk.

Xbryk is recommended for approval for the treatment of adult and skeletally mature adolescent patients with giant cell tumor of bone that is unresectable or in whom surgical resection is likely to result in severe morbidity. This agent has also been recommended for approval for the prevention of skeletal-related events, such as radiation to bone, pathological fracture, surgery to bone, or spinal cord compression in adult patients with advanced malignancies involving bone.

This positive CHMP opinion was supported by analytical data, clinical data, and nonclinical data, including findings from a randomized, double-blind, parallel-group, 3-arm, single-dose phase 1 trial (NCT04621318) that showed the pharmacokinetic equivalence between single, subcutaneous, 60-mg doses of SB16, United States–sourced denosumab (Prolia), and European Union–sourced denosumab (Prolia) in 168 healthy male participants who were randomly assigned 1:1:1 among the 3 arms. Participants were eligible for enrollment if they were ages 28 to 55 years, had a body weight between 60.0 and 90.0 kg, had a body mass index between 20.0 and 29.9 kg/m², and had 12-lead electrocardiogram results and vital sign results without clinically significant abnormal findings.² Investigators evaluated pharmacokinetics, pharmacodynamics, safety, tolerability, and immunogenicity for 197 days.^1,2 This trial met its primary pharmacokinetic end points, including the area under the concentration-time curve from time 0 to infinity and the maximum serum concentration.¹

Furthermore, a randomized, multicenter, double-blind phase 3 trial (NCT04664959) enrolled 457 postmenopausal patients with osteoporosis who were randomly assigned 1:1 to receive 60 mg of either SB16 or reference denosumab subcutaneously at months 0, 6, and 12. At month 12, patients in the reference denosumab arm were randomly assigned for a second time in a 1:1 ratio to switch to receiving SB16 or maintain treatment with reference denosumab.

This trial enrolled patients ages 55 to 80 years who were ambulatory and visually unimpaired at screening.³ Patients needed to have an absolute bone mineral density consistent with T-score at the total hip or lumbar spine at –4 and –2.5, evaluable joints, and a body weight of 50 kg to 90 kg.

This study showed equivalent efficacy outcomes and comparable safety, immunogenicity, pharmacokinetic, and pharmacodynamic profiles between the 2 formulations.¹ The trial met its primary end point of percent change from baseline in lumbar spine bone mineral density at month 12. Follow-up data from month 18 showed that switching to SB16 from reference denosumab generated comparable efficacy, pharmacokinetic, pharmacodynamic, safety, and immunogenicity outcomes up to month 18.

“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 [QOL] of patients. Enhancing access to treatment options is essential for improving both patient outcomes and QOL, as it allows timely treatment for patients,” Byoungin Jung, vice president and leader of the Regulatory Affairs Team at Samsung Bioepis, stated in a news release. “If approved, [SB16] would become our first endocrinology biosimilar, adding to our growing portfolio of biosimilar products that are helping to improve patients’ QOL and access to treatments, and relieve the financial burden of health care systems.”

References

1. Samsung Bioepis receives positive CHMP opinion for denosumab biosimilars, Obodence and Xbryk. News release. Samsung Bioepis Co., Ltd. November 15, 2024. Accessed November 15, 2024. https://www.samsungbioepis.com/en/newsroom/newsroomView.do?idx=422&currentPage=1
2. Pharmacokinetics, pharmacodynamics, safety, tolerability, and immunogenicity study of SB16 in healthy male subjects. ClinicalTrials.gov. Updated November 28, 2022. Accessed November 15, 2024. https://www.clinicaltrials.gov/study/NCT04621318
3. A study to compare SB16 (proposed denosumab biosimilar) to Prolia in postmenopausal women with osteoporosis. ClinicalTrials.gov. Updated December 20, 2022. Accessed November 15, 2024. https://www.clinicaltrials.gov/study/NCT04664959