FDA Approves Second Biosimilars for Prolia/Xgeva

The FDA has approved Samsung Bioepis’ biosimilars of Amgen’s Prolia and Xgeva and granted the therapies interchangeability designation. No information is available on when the drugs will launch or on the price.

Ospomyv (denosumab-dssb; SB16; 60 mg pre-filled syringe), which references Prolia, has been approved to treat several conditions, including men and postmenopausal women with osteoporosis at high risk for fracture, as well as to increase bone mass in men receiving androgen deprivation therapy for nonmetastatic prostate cancer, and for women receiving adjuvant aromatase inhibitor therapy for breast cancer.

Osteoporosis is a bone disease that develops when bone mineral density and bone mass decrease or when bone strength and structure change. It is a common bone disease and results in weakening of bone tissue, bone structure, and strength, and may lead to increased risk of fractures. According to the CDC, more than 10 million U.S. adults aged 50 and over live with osteoporosis, a major cause of fractures in postmenopausal women and in older men. Osteoporosis is responsible for an estimated two million broken bones per year.

Xbryk (denosumab-dssb; SB16; 120 mg vial), which references Xgeva, has been approved to prevent skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors. Bone is the third most frequent site for metastatic tumors. Nearly all types of cancer can spread to the bone and cause pain and fractures, though cancers that often metastasize in bones include breast and prostate.

The American Cancer Society estimates that there will be 3,770 new cases of primary bone cancer this year, with 2,190 deaths. In cancer that metastasize to the bone, survival rates ranging from 6 to 7 months in lung cancer to several years in the breast cancer.

The FDA approval of the biosimilars was based on totality of evidence including analytical, non-clinical data, and clinical data. A randomized, double-blind, three-arm, parallel group, single-dose phase 1 study demonstrated the pharmacokinetic (PK) equivalence between SB16, EU-sourced denosumab, and U.S.-sourced denosumab in healthy male participants. The primary pharmacokinetic endpoints were met. In addition, a randomized, double-blind, multi-center phase 3 study demonstrated equivalent efficacy and comparable safety, immunogenicity, pharmacokinetic, and pharmacodynamics (PD) profiles between SB16 and reference denosumab in postmenopausal osteoporosis patients.

The biosimilars will contain a boxed warning about the risk of hypocalcemia (low calcium levels) in patients with advanced kidney disease.

Related: FDA Approves First Biosimilars for Prolia and Xgeva

The FDA had approved the first biosimilars of Prolia and Xgeva in March 2024. Sandoz’s Wyost and Jubbonti are also interchangeable for the reference products and are approved for all of the same indications in osteoporosis and bone cancer.

A third biosimilar of Prolia/Xgeva is under review by regulators. In October 2024, the FDA accepted Organon’s biologic license application for HLX14. Organon, which acquired the commercialization rights from Shanghai Henlius Biotech, anticipates hearing from regulatory authorities about the HLX14 application by mid-year 2025, a spokesperson said at the time.

Denosumab is a human monoclonal antibody designed to bind to the RANKL protein, an activator of osteoclasts (cells involved in breaking down bone tissue). By binding to and inhibiting RANKL, denosumab decreases the production and activity of osteoclasts, resulting in a reduction of bone loss, and subsequently the likelihood of fractures and other serious bone conditions.