EU-Wide Sales Approval Secured

The European Commission approved Celltrion's Osenvelt (denosumab) on February 14, 2025. This final marketing authorization follows the positive opinion adopted by the Committee for Medicinal Products for Human Use (CHMP) under the European Medicines Agency (EMA) on December 12, 2024. Osenvelt is an approved biosimilar, not a clinical development candidate, and will enter the prescription market after undergoing country-specific pricing and reimbursement decisions and supply agreements.

Targeting All Indications of Xgeva with RANKL Inhibitor

The active ingredient in Osenvelt, denosumab, is a human monoclonal antibody that blocks RANK ligand (RANKL), which promotes osteoclast formation. It is approved for the prevention of skeletal-related complications in adult patients with bone metastases from cancer and multiple myeloma, and for the treatment of giant cell tumor of bone in adults and adolescents with open growth plates where surgical resection is not feasible or would result in severe morbidity. Based on brand, active ingredient, and target, Osenvelt, denosumab, and RANKL are the key elements. While hypercalcemia of malignancy is a factor, the EU approval primarily focuses on skeletal-related events and giant cell tumor of bone.

Clinical Equivalence as the Basis for Approval

The EMA determined that Osenvelt is highly similar to Amgen's reference product, Xgeva, in terms of structure, purity, biological activity, and pharmacokinetics. In a comparative clinical trial involving 479 postmenopausal women, lumbar bone mineral density increased by approximately 5% in both the Osenvelt and Prolia groups after one year. Due to the application of the totality of evidence approach for biosimilars, efficacy was extrapolated to each indication of Xgeva without repeating large-scale confirmatory clinical trials. Hypocalcemia and osteonecrosis of the jaw remain key safety management considerations, consistent with the reference product.

Triggering Price Competition in a Major Franchise

Amgen's 2024 Xgeva sales were USD 2.225 billion, and sales of the osteoporosis product with the same active ingredient, Prolia, were USD 4.374 billion, bringing the total denosumab franchise to USD 6.599 billion. Osenvelt will compete with Xgeva and zoledronic acid in patients with bone metastases, and also directly compete with Sandoz's Wyost and Samsung Bioepis's Xbryk, which are EU-approved biosimilars. With the expiration of RANKL antibody patents in some European countries in November 2025, this approval simultaneously establishes a regulatory basis for Celltrion to expand its oncology and bone disease portfolio and erode Amgen's sales.