The FDA has approved two new drugs that are biosimilars to denosumab, adding to the ever-expanding field of less expensive options of the popular anti-osteoporosis and cancer-related bone loss drug; however, savings on such drugs so far have been modest.

The two new approvals are for Enoby and Xtrenbo (both denosumab-qbde, Gedeon Richter Plc. or Hikma Pharmaceuticals Plc.), designed with mechanisms similar to Amgen’s denosumab products, Prolia and Xgeva.

The approvals were granted on the basis of evidence including a double-blind, phase 3 clinical trial of 473 women with postmenopausal osteoporosis, with results showing denosumab-qbde (then referred to as RGB-14-P for osteoporosis and RGB-14-X for the oncology indications) to have comparable efficacy, safety, and immunogenicity compared with denosumab.

“Denosumab biosimilars have the potential to improve treatment access for people with osteoporosis by providing high-quality, lower-cost alternatives to originator denosumab, with the same mechanism of action and a comparable efficacy and safety profile,” the study authors wrote.

Enoby

Like Prolia, Enoby is approved for the treatment of osteoporosis in postmenopausal women at high risk for fracture and to increase bone mass in men with osteoporosis at high risk for fracture.

Other indications include glucocorticoid-induced osteoporosis in men and women at high risk for fracture and increasing bone mass in men at high risk for fracture related to androgen deprivation therapy for nonmetastatic prostate cancer.

Enoby is also indicated to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.

Xtrenbo

Xtrenbo, like Xgeva, is approved for the prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors.

The indications also include treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or when surgical resection is likely to result in severe morbidity, and to treat hypercalcemia of malignancy refractory to bisphosphonate therapy.

Enoby is available in a 60-mg/mL single-dose prefilled syringe for subcutaneous injection, while Xtrenbo is provided as a 120-mg/1.7 mL single-dose vial.

The Need for Lower-Cost Options in the US

Denosumab, a monoclonal antibody administered subcutaneously once every 6 months with Prolia and every 4 weeks with Xgeva, has been shown to reduce the risk for vertebral, hip, and nonvertebral fractures in the variety of settings covered by the biosimilars’ indications.

While the drug has been shown to offer greater improvements than bisphosphonate osteoporosis drugs in measures such as overall bone mineral density, denosumab’s higher costs compared with bisphosphonates can be a barrier for many, particularly in the US.

With the high cost, a high demand for less expensive biosimilars can be expected, and many are hitting the market — the approvals of Enoby and Xtrenbo represent the seventh and eighth biosimilar drugs to be approved in the US, while as many as 21 denosumab biosimilars, developed by 10 different companies, had been approved in Europe as of August 2025.

However, so far, the relative reduction in price for the biosimilars in the US has only been modest, with other biosimilars, including Jubbonti (denosumab-bbdz, Sandoz) and Stoboclo (denosumab-bmwo, Celltrion), for instance, having recently reported list prices that were only approximately 5%-14% lower than the 2025 wholesale acquisition cost for denosumab of $1875 per dose before any discounts or rebates.

Costs Lower in Europe

Meanwhile, in Europe, where biosimilars are typically available at a small fraction of the cost seen in the US, the denosumab biosimilars are a very welcome alternative, Muhammad K. Nisar, MD, consultant rheumatologist and physician at Luton & Dunstable University Hospital, Luton, England, told Medscape Medical News.

“Clinicians feel very comfortable with [denosumab] biosimilars, with great belief in their efficacy and safety,” he said.

Nisar, a strong proponent of biosimilars, noted that “in the UK, we switched to use of more than 90% biosimilars within first year of their launch.”

He detailed the substantially lower prices of biosimilars under European health system models than those in the US.

“We’re expecting the biosimilars to be 50% cheaper than Prolia and Xgeva in year 1, and ultimately, they should be available at only 15%-20% of [those drugs’] prices.”

Nisar reported receiving support including attendance at conferences, speaker fees, and/or honoraria from Alfasigma, Boehringer Ingelheim, medac Pharma, Roche, Chugai, MSD, AbbVie, Pfizer, BMS, Novartis, Celgene, UCB, Flynn Pharma, and Eli Lilly and Company.