Denosumab-bnht Biosimilar Receives FDA Approval

The FDA has approved the biologics license application (BLA) for denosumab-bnht (Conexxence, Bomyntra) as biosimilars to denosumab (Prolia and Xgeva, respectively) for all indications of the reference products.¹ This includes osteoporosis in women who have an increased risk for fractures after menopause, osteoporosis in men, and osteoporosis in patients using steroid medicines for at least 6 months.²

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Denosumab is also indicated to treat bone loss in men with prostate cancer and women with breast cancer who are at high risk for fracture prior to receiving treatment for non-metastatic cancer. Additionally, the drug is used to prevent bone issues in individuals with multiple myeloma and bone metastases from tumors. Teenagers with giant cell tumor of the bone that cannot be removed by surgery could also be treated with denosumab; however, the safety and efficacy for other pediatric conditions have not been established. Lastly, denosumab is also indicated for hypercalcemia of malignancy that has been treated with bisphosphonates.²

Denosumab is commonly administered as a shot on the upper arm, high thigh, or stomach, once every 6 months for Prolia or the biosimilar Conexxence, and once every 4 weeks for Xgeva or its biosimilar Bomyntra.^1,2

With the current approval, Conexxence is indicated to treat individuals that face an increased risk for fractures, including those with osteoporosis, along with individuals undergoing cancer treatments that impact bone density and individuals receiving long-term glucocorticoid therapy. However, the study authors noted that it has a black box warning in the US for altering the risk of severe hypocalcemia among individuals with advanced chronic kidney diseases and individuals on dialysis.¹

Like the reference product, Bomyntra is approved to prevent skeletal-related events among individuals with multiple myeloma and bone metastases from solid tumors, hypercalcemia, and giant tumor of the bone in adults and skeletally mature adolescents.¹

The FDA approval was based on thorough analytical development and a similarity assessment. The study authors noted that this was reinforced by 2 clinical studies. One study focused on pharmacokinetics, pharmacodynamics, and immunogenicity in healthy volunteers. The second study evaluated efficacy, pharmacodynamics, safety, and immunogenicity in women with postmenopausal osteoporosis.¹

The studies included 3 large-scale trials (NCT00321464, NCT00330759, and NCT00321620), which involved over 5700 individuals with bone metastases from solid tumors, comparing the effectiveness of denosumab to zoledronic acid in preventing skeletal-related events (SREs). Results from these trials consistently showed that denosumab significantly delayed the time to the first SRE compared to zoledronic acid, indicating a superior outcome. The findings suggest that denosumab is an effective treatment option for preventing bone complications among individuals with bone metastases.³

“We are pleased to have reached a global settlement with Amgen for our denosumab biosimilar candidates and to continue to provide patients around the globe with access to high-quality biological medicines. This marks our sixth FDA biosimilar approval, expanding our portfolio to provide more affordable therapies to patients in the US.,” Sang Jin Pak, MD, president of Fresenius Kabi Biopharma, said in a news release.¹

REFERENCES

1. Fresenius Receives FDA Approval for their Denosumab Biosimilars and Secures Global Settlement Agreement. BioSpace. News release. March 27, 2025. Accessed March 27, 2025. https://www.biospace.com/press-releases/fresenius-receives-fda-approval-for-their-denosumab-biosimilars-and-secures-global-settlement-agreement

2. Denosumab (subcutaneous route). Mayo Clinic. News release. Updated March 1, 2025. Accessed March 27, 2025. https://www.mayoclinic.org/drugs-supplements/denosumab-subcutaneous-route/description/drg-20074315

3. A Study Comparing Denosumab vs. Zoledronic Acid for the Treatment of Bone Metastases in Breast Cancer Subjects. ClinicalTrials.gov. Updated November 8, 2022. Accessed March 27, 2025. https://clinicaltrials.gov/study/NCT00321464?tab=results