FDA Approves Denosumab-Bnht as Biosimilar to Prolia, Xgeva
Denosumab-bnht (Conexxence, Bomyntra) became the third biosimilar in 2025 to be approved for denosumab (Prolia, Xgeva).
The FDA approved denosumab-bnht (Conexxence, Bomyntra) as biosimilars to denosumab (Prolia, Xgeva, respectively) for all indications of the reference product. Denosumab is used to treat osteoporosis in women with an increased risk of fractures after menopause and osteoporosis in men, according to Mayo Clinic.1,2
Denosumab-bnht (Conexxence, Bomyntra) became the third biosimilar in 2025 to be approved for denosumab (Prolia, Xgeva). | Image Credit: sunnychicka | stock.adobe.com
The drug has also been used to treat bone loss for men and women with prostate and breast cancer, respectively, who are at a high risk of fracture due to their treatment. The medication can cause hypercalcemia for children with bone issues, and the safety and efficacy are not established for pediatric patients. It is typically administered by a physician or other health care professional as a subcutaneous injection on the upper arm, upper thigh, or stomach.
Prolia, with the biosimilar Conexxence, is usually given every 6 months, and Xgeva, with the biosimilar Bomyntra, is usually given once every 4 weeks, according to Mayo Clinic.2
For Bomyntra, there were 3 trials that investigated the drug for patients with bone metastases, showing that overall survival and progression-free survival were similar across all 3 trials. In all trials, individuals randomly received 120 mg of denosumab subcutaneously every 4 weeks or 4 mg of zoledronic acid intravenously every 4 weeks. The primary outcome was noninferiority of time to first skeletal-related event (SRE) compared with zoledronic acid. Secondary outcomes included time to first SRE and superior time to first and subsequent SRE.
Study 20050136 (NCT00321464) enrolled 2046 patients, study 20050244 (NCT00330759) enrolled 1776 patients, and study 20050103 (NCT00321620) enrolled 1901 patients. The results showed that the time to SRE was delayed with the biosimilar denosumab compared with zoledronic acid.3
For Conexxence, the efficacy of the biosimilar was shown for postmenopausal osteoporosis. There were 7808 patients enrolled, and biosimilar denosumab reduced the incidence of new morphometric vertebral fractures for 1, 2, and 3 years. There were fewer patients (0.7%) taking denosumab that experienced hip fractures compared with the placebo (1.2%) at 3 years. For bone mineral density (BMD), the denosumab biosimilar increased BMD at 3 years for the lumbar spine, total hip, and femoral neck. Results were similar across patients with glucocorticoid-induced osteoporosis, bone loss for men with prostate cancer, and bone loss for women with breast cancer.3
The first biosimilar for denosumab was approved in 2024, and denosumab-bbdz (Wyost/Jubboti) were the first approved with interchangeability status. In February 2025, the FDA also approved denosumab-dssb (Ospomyv, Xbryk), which referenced Prolia and Xgeva, respectively. Both drugs were also granted provisional determination for interchangeability designation.4
Additionally, earlier in March 2025, the FDA approved denosumab-bmwo (Stoboclo, Osenvelt) for the indications of Prolia and Xgeva, respectively. Denosumab-bnht has become the third biosimilar in 2025 to be approved as a biosimilar to the reference products.5
