FDA Approves 2 Denosumab Biosimilars for All Reference Medicine Indications

FDA

The FDA has approved the biosimilars denosumab-bddz (Wyost) and denosumab-bddz (Jubbonti) for use in all indications of the reference medicines denosumab (Xgeva) and denosumab (Prolia).

Wyost is approved for the prevention of skeletal-related events (SREs) in patients with multiple myeloma and patients with bone metastases from solid tumors; for the treatment of adult and skeletally mature adolescent patients with giant cell tumor of the bone that is unresectable or where surgical resection is likely to result in severe morbidity; and for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy.

Additionally, Jubbonti is approved for the treatment of postmenopausal women with osteoporosis at high risk for fracture; to increase bone mass in men with osteoporosis at high risk for fracture; for the treatment of glucocorticoid-induced osteoporosis in men and women at high risk for fracture; to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer; and to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.

The regulatory agency also approved Sandoz’s Jubbonti Risk Evaluation and Mitigation Strategy (REMS) program, which is intended to inform physicians and patients about the risk of severe hypocalcemia associated with the biosimilar in patients with advanced chronic kidney disease, including patients dependent on dialysis.

"Sandoz has achieved the first FDA approval for biosimilars to denosumab, a medicine that can address primary and secondary bone loss, such as osteoporosis, as well as cancer-related skeletal events, which are disease states that can profoundly reduce quality of life for patients," Keren Haruvi, president of Sandoz North America, stated in a news release. "I am proud that Sandoz continues to pioneer access to these life-changing medicines for the patients who need them most."

Wyost and Jubbonti both feature the same dosage form, method of administration, dosing regimen, and presentation as their respective reference medicines. Wyost is approved as a 120 mg/1.7 mL (70 mg/mL) injection, and Jubbonti was authorized as a 60 mg/mL injection.

Contraindications for Wyost include hypocalcemia and known significant hypersensitivity to denosumab products.

Regarding the safety of Wyost, the most common adverse effects (AEs) reported in at least 25% of patients with bone metastasis from solid tumors included fatigue/asthenia, hypophosphatemia, and nausea. In patients with multiple myeloma, the most common AEs observed in at least 10% of patients were diarrhea, nausea, anemia, back pain, thrombocytopenia, peripheral edema, hypocalcemia, upper respiratory tract infection, rash, and headache. Common AEs that occurred in at least 10% of patients with giant cell tumor of the bone were arthralgia, headache, nausea, back pain, fatigue, and pain in extremity. In those with hypercalcemia of malignancy, the most common AEs that occurred in more than 20% of patients were nausea, dyspnea, decreased appetite, headache, peripheral edema, vomiting, anemia, constipation, and diarrhea.

Notably, Jubbonti carries a boxed warning stating that patients with advanced chronic kidney disease are at risk of severe hypocalcemia following treatment administration, as severe hypocalcemia requiring hospitalization, life-threatening events, and fatal cases have been reported. Additionally, chronic kidney disease-mineral bone disorder (CKD-MBD) is associated with an increased risk of hypocalcemia. Prior to receiving Jubbonti, patients with advanced chronic kidney disease should be evaluated for the presence of CKD-MBD, and it is recommended that treatment with Jubbonti should be supervised by a health-care provider with expertise in the diagnosis and management of CKD-MBD.

Additional safety data showed that in patients with bone loss due to hormone ablation for cancer, the most common AEs reported in at least 10% of patients that were more common than placebo included arthralgia and back pain.

Reference

Sandoz receives FDA approval for first and only denosumab biosimilars. News release. Sandoz. March 5, 2024. Accessed March 5, 2024. https://us.sandoz.com/sandoz-receives-fda-approval-first-and-only-denosumab-biosimilars/