## Denosumab Biosimilars Gain Interchangeability Status
The FDA has designated two denosumab biosimilars,Stoboclo and Osenvelt (denosumab-bmwo; celltrion USA),as interchangeable biosimilars to their respective reference products,Prolia and Xgeva (Amgen),for all approved indications,effective october 29,2025.1 Along with Conexxence and Bomyntra (denosumab-bnht; Fresenius Kabi), this is the second pair of denosumab biosimilars to recently receive this status.2
FDA Approves Interchangeable Biosimilars for Denosumab
Table of Contents
The FDA has granted interchangeability designations to two denosumab biosimilars: Stoboclo (CT-P41) and Osenvelt. These approvals expand treatment options for conditions like osteoporosis and bone metastases.
Indications
Denosumab, and now its interchangeable biosimilars, are indicated for:
* Women with osteoporosis at high risk for fracture.
* Men with osteoporosis at high risk for fracture,or men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer.
* Glucocorticoid-induced osteoporosis in men and women who are at high risk of bone fracture.
* Women who are at high risk of fracture and are receiving an adjuvant aromatase inhibitor therapy for breast cancer.
Osenvelt is also indicated to:
* Prevent skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors.
* Treat adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity.
* Treat hypercalcemia of malignancy refractory to bisphosphonate therapy.
Interchangeability & Clinical Data
The interchangeability designation allows these biosimilars to be substituted for the reference product at the pharmacy level without requiring prescriber consultation, though this is subject to state laws. This designation was supported by robust clinical evidence, including phase 3 trials evaluating safety, efficacy, pharmacodynamics, pharmacokinetics, and immunogenicity.
A key study (NCT04757376) demonstrated equivalence between CT-P41 and denosumab in postmenopausal women with osteoporosis. The 18-month, double-blind, randomized study involved 479 patients initially assigned to either CT-P41 or denosumab. After 52 weeks, those initially on the biosimilar continued, while those on denosumab were randomized to continue denosumab or switch to the biosimilar.
Results showed equivalence for primary efficacy (LS mean difference: -0.139 [95% CI -0.826, 0.548]) and pharmacodynamics (geometric LS mean ratio: 94.94 [95% CI 90.75, 99.32]).Secondary efficacy, pharmacodynamics, pharmacokinetics, and safety were comparable across all groups up to week 78, even after switching.
Denosumab Biosimilars Receive Interchangeability Designation
The FDA recently approved two biosimilars referencing denosumab (Prolia) as interchangeable. These approvals mark a significant step in increasing access to more affordable treatment options for osteoporosis and cancer-related bone events. The biosimilars are Conexxence (Amgen) and Bomyntra (Celltrion).
What Does Interchangeability Mean?
Interchangeability isn’t the same as a standard biosimilar approval. An interchangeable biosimilar can be substituted for the reference product by a pharmacist without the intervention of the prescribing physician, similar to how generic drugs are substituted. This streamlines treatment and perhaps lowers costs for patients.
About Denosumab and its Uses
Denosumab is a human monoclonal antibody that works by inhibiting RANK ligand, a protein essential for the formation, function, and survival of osteoclasts – the cells that break down bone. It’s primarily used to:
- Treat osteoporosis in postmenopausal women and men at high risk for fractures.
- Prevent skeletal-related events (fractures, spinal cord compression, etc.) in patients with bone metastases from solid tumors.
- Treat giant cell tumor of bone.
Conexxence and Bomyntra: What You Need to Know
Both Conexxence and Bomyntra have demonstrated biosimilarity to Prolia through rigorous analytical testing, animal studies, and clinical trials. The FDA’s interchangeability designation confirms these biosimilars produce the same clinical affect as the reference product.
Conexxence received its initial biosimilar approval in December 2023 and the interchangeability designation in March 2025. Pharmacy Times reports this approval expands treatment options for patients.
Bomyntra was approved as a biosimilar in May 2024 and granted interchangeability in March 2025. According to Pharmacy Times,this provides another cost-effective choice to Prolia.
implications for Patients and Healthcare Providers
The availability of interchangeable denosumab biosimilars is expected to:
- Increase competition in the market, potentially lowering drug costs.
- Provide more treatment options for patients.
- simplify the process of accessing treatment, as pharmacists can substitute biosimilars without requiring a new prescription.
Healthcare providers should familiarize themselves with biosimilars and their interchangeability status to make informed prescribing decisions. Patients should discuss any concerns or questions they have with their doctor or pharmacist.