FDA approved Jubbonti (denosumab-bbdz) injection as an interchangeable biosimilar to U.S.-licensed Prolia (denosumab), and Wyost (denosumab-bbdz) injection as an interchangeable biosimilar to U.S.-licensed Xgeva (denosumab).
These products bind to RANKL (receptor activator of nuclear factor kappa beta ligand), blocking its ability to bind to its receptor, a protein called RANK. Inhibition of the RANKL/RANK interaction helps prevent bone cells called osteoclasts from breaking down bone in the body. This is the first interchangeable biosimilar for a RANKL inhibitor.
Jubbonti is approved for the following treatment indications, which are also currently approved for Prolia:
• postmenopausal women with osteoporosis at high risk for fracture;
• increasing bone mass in men with osteoporosis at high risk for fracture;
• glucocorticoid-induced osteoporosis in men and women at high risk for fracture;
• increasing bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer; and
• increasing bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.
Wyost is approved for the following treatment indications, which are also currently approved for Xgeva:
• prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors;
• treatment of 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
• treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy.
Both Jubbonti and Wyost are administered by subcutaneous injection and may be taken along with calcium and vitamin D as necessary to treat or prevent low calcium levels.
Disease or Condition
Osteoporosis
Osteoporosis is a bone disease that develops when bone mineral density and bone mass decrease, or when the structure and strength of bone changes. This can lead to a decrease in bone strength that can increase the risk of fractures (broken bones). Osteoporosis is a “silent” disease because patients typically do not have symptoms and may not even know they have the disease until they break a bone. Osteoporosis is the major cause of fractures in postmenopausal women and in older men. Fractures can occur in any bone but happen most often in bones of the hip, vertebrae in the spine, and wrist.
In addition to treatment of osteoporosis, Jubbonti may also be used to increase bone mass and reduce the risk of bone fracture in patients with cancer (tumors) in the prostate gland (men) or in the breasts (women and men).
Bone complications from cancer
For patients with multiple myeloma or bone metastases (when the cancer spread to the bones from tumors in other parts of the body), complications can arise such as fractures, need for radiation to the bone, or spinal cord compression. Some patients with bone cancer may experience high calcium levels in the blood (hypercalcemia).
Giant Cell Tumor of Bone
Giant cell tumor of bone is a non-cancerous tumor that typically affects the ends of bones near a joint. Wyost is approved to treat this disease in adults or skeletally mature adolescents where the tumor has either recurred, or surgery is not feasible.
Approval Information
A biosimilar is a biological product that is highly similar to, and has no clinically meaningful differences from, a biological product already approved by FDA (also called the reference product). This means patients can expect the same safety and effectiveness from the biosimilar as they would the reference product.
An interchangeable biosimilar is a biosimilar that has met other requirements under the law and may be substituted for the reference product without consulting the prescriber. The substitution may occur at the pharmacy, subject to state pharmacy laws which vary by state, a practice commonly called “pharmacy-level substitution” — similar to how generic drugs are substituted for brand name drugs.
All biological products are approved only after they meet FDA’s rigorous approval standards. This means health care providers and patients can expect the same safety and effectiveness from both a biosimilar and an interchangeable biosimilar, just as they would for a reference product. Biosimilar and interchangeable biosimilar products may cost less than the brand-name medicine (i.e., reference product).
FDA’s approval of Jubbonti and Wyost is based on a comprehensive review of scientific evidence demonstrating the products are highly similar to Prolia and Xgeva, respectively, and that there are no clinically meaningful differences between the two product pairs. This evidence included comparisons of the products on an analytical level using an extensive battery of physicochemical tests and biological assays.
Multiple lots manufactured for each product were compared across a broad range of different product quality attributes, and the results of these comparisons confirmed similarity in the structural and functional features of Jubbonti and Wyost with Prolia and Xgeva, including those known to impact safety and efficacy. The comparative clinical data to support approval of Jubbonti and Wyost included results from a pharmacokinetic study in healthy adult subjects that confirmed similar exposure following a single subcutaneous injection. In addition, a study in postmenopausal women with osteoporosis was conducted and demonstrated similarity in efficacy, safety, and immunogenicity. The totality of these data supported FDA approval of Jubbonti and Wyost as an interchangeable biosimilar to Prolia and Xgeva, respectively.
Safety Information for Jubbonti and Wyost
The side effects and adverse events observed in clinical trials of Jubbonti and Wyost are consistent with those observed with Prolia and Xgeva.
• The most common side effects of Jubbonti, like Prolia, were low blood calcium; back, joint, arm, leg and muscle pain;, common cold (runny nose or sore throat), and arthritis.
• The most common side effects of Wyost, like Xgeva, are tiredness/weakness, low phosphate levels in your blood, diarrhea, nausea, low red blood cells, low blood platelets and calcium levels, back pain, swelling of the lower legs or hands, upper respiratory tract infection, rash, and headache.
Denosumab can cause serious side effects including serious infections, skin reactions, osteonecrosis, allergic reactions and hypocalcemia. It is unknown if the long-term use of denosumab time may cause slow healing of broken bones.
On January 19, 2024, FDA issued a Drug Safety Communication update to report that the agency added a boxed warning for increased risk of severe hypocalcemia (low blood calcium levels) in patients with advanced chronic kidney disease taking osteoporosis medicine Prolia (denosumab). Jubbonti also has a boxed warning in the prescribing information, just as Prolia does. Patients on dialysis or with mineral and bone disorders are at highest risk for this adverse event.
