FDA OKs First Interchangeable Biosimilars for Denosumab

The FDA approved injectable Jubbonti and Wyost as the first interchangeable biosimilars to denosumab (Prolia, Xgeva), and for all the same indications, including the prevention of fractures in at-risk adults and skeletal-related events in cancer patients.

A review of the evidence showed the biosimilars to be “highly similar” to the reference biologics and with “no clinically meaningful differences between the two product pairs,” the agency said in its announcement on Tuesday. Depending on state laws, interchangeable biosimilars allow for pharmacy-level substitutions, meaning a pharmacist can switch to the biosimilar without consulting the prescriber.

However, exactly when the new agents will make their way to the clinic is murky, according to the drugmaker. “Given ongoing patent litigation around these products, Sandoz will not comment on anticipated launch timing or other launch details at this time,” the company said in a press release.

The biosimilars will have the same dosages and route of administration as the reference medicines.

Jubbonti (60 mg/1 mL) is approved for the same indications as Prolia, which include 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; treating glucocorticoid-induced osteoporosis in men and women at high risk for fracture; and to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer and in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.

Wyost (120 mg/1.7 mL), meanwhile, will carry the same indications as Xgeva, including for preventing skeletal-related events in multiple myeloma patients and in solid-tumor patients with bone metastases; for treating adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity; and to treat hypercalcemia of malignancy refractory to bisphosphonate therapy.

Denosumab is a RANKL inhibitor that works by binding to a receptor activator of nuclear factor kappa beta ligand, blocking its ability to bind to its protein receptor, RANK. This process helps prevent osteoclasts from breaking down bone in the body.

The side effect profiles are similar between the biosimilars and their reference products, the FDA said.

Common side effects with Jubbonti include low blood calcium; back, joint, arm, leg, and muscle pain; the common cold; and arthritis. Like the original product, the drug will carry a boxed warning regarding an increased risk of severe hypocalcemia in patients with advanced chronic kidney disease, especially for patients on dialysis or with mineral and bone disorders.

Side effects with Wyost include tiredness and weakness, low phosphate levels in the blood, diarrhea, nausea, low red blood cells, low blood platelets, low calcium levels, back pain, swelling of the lower legs or hands, upper respiratory tract infection, rash, and headache.

Denosumab can be taken along with calcium and vitamin D as necessary to treat or prevent low calcium levels.

According to the Center for Biosimilars, this approval marks the 47th biosimilar approved by the FDA and ninth to receive an interchangeability designation.

Please enable JavaScript to view the

comments powered by Disqus.