XGEVA

What it is

Xgeva is denosumab (rch) . Denosumab is a fully human IgG2 monoclonal antibody with high affinity and specificity for RANK ligand (RANKL) . Xgeva is supplied as a sterile, preservative-free, clear, colourless to slightly yellow solution for subcutaneous (SC) injection . It is available in two formulations: each vial contains 120 mg denosumab in 1.7 mL of solution (70 mg/mL), and each pre-filled syringe contains 120 mg denosumab in 1.0 mL of solution (120 mg/mL) .

Approved indications

— Prevention of skeletal related events in patients with multiple myeloma and in patients with bone metastases from solid tumours. — Treatment of giant cell tumour of bone in adults or skeletally mature adolescents that is recurrent, or unresectable, or resectable but associated with severe morbidity. — Treatment of hypercalcaemia of malignancy that is refractory to intravenous bisphosphonate.

Dosing overview

The recommended dose of Xgeva for the prevention of skeletal related events is 120 mg administered as a single subcutaneous injection once every 4 weeks into the thigh, abdomen or upper arm . The recommended dose of Xgeva for the treatment of giant cell tumour of bone and hypercalcaemia of malignancy is 120 mg administered as a single subcutaneous injection once every 4 weeks into the thigh, abdomen or upper arm with a loading dose of 120 mg on days 8 and 15 of the initial 4-week treatment period . Daily supplementation with at least 500 mg calcium and 400 IU vitamin D is required in all patients, unless hypercalcaemia is present .

Key safety warnings

Pre-existing hypocalcaemia must be corrected prior to initiating therapy with Xgeva. Supplementation with calcium and vitamin D is required in all patients unless hypercalcaemia is present . Hypocalcaemia can occur at any time during therapy with Xgeva. Monitoring of calcium levels should be conducted prior to the initial dose of Xgeva, within two weeks after the initial dose, and if suspected symptoms of hypocalcaemia occur . In the post-marketing setting, severe symptomatic hypocalcaemia (including fatal cases) has been reported, with most cases occurring in the first weeks of initiating therapy, but can occur later . Osteonecrosis of the jaw (ONJ) has occurred in patients treated with denosumab, with the majority of cases occurring within 5 months after the last dose. In clinical trials, the incidence of ONJ was higher with longer duration of exposure . An oral examination should be performed by the prescriber prior to initiation of Xgeva treatment and a dental examination with appropriate preventive dentistry is recommended prior to treatment with Xgeva, especially in patients with risk factors for ONJ . Good oral hygiene practices should be maintained during treatment with Xgeva. Patients should avoid invasive dental procedures during treatment with Xgeva . Atypical femoral fracture has been reported with Xgeva. Atypical femoral fractures may occur with little or no trauma in the subtrochanteric and diaphyseal regions of the femur and may be bilateral . During Xgeva treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Patients presenting with such symptoms should be evaluated for an incomplete femoral fracture, and the contralateral femur should also be examined . Clinically significant hypercalcaemia requiring hospitalisation and complicated by acute renal injury has been reported in Xgeva-treated patients with giant cell tumour of bone and patients with growing skeletons weeks to months following treatment discontinuation . Multiple vertebral fractures (MVF), not due to bone metastases, may occur following discontinuation of treatment with Xgeva, particularly in patients with risk factors such as osteoporosis or prior fractures. Advise patients not to interrupt Xgeva therapy without their physician's advice .

Contraindications

Xgeva is contraindicated in pregnancy . Xgeva is contraindicated in patients with hypersensitivity to the active substance, to CHO-derived proteins or to any of the excipients . Severe untreated hypocalcaemia is a contraindication . Unhealed lesions from dental or oral surgery are a contraindication .

PBS listing

Xgeva 120 mg in 1 mL single use pre-filled syringe is listed on the PBS with streamlined authority required restriction, with an ex-manufacturer price of A$301.39 .

Regulatory history

Xgeva denosumab 70 mg/mL (120 mg/1.7 mL) solution for injection vial was first listed on the ARTG on 2011-09-08 . In December 2013, the TGA approved denosumab for the treatment of giant cell tumour of bone in adults or skeletally mature adolescents that is recurrent, or unresectable, or resectable but associated with severe morbidity . In July 2016, the PBAC recommended a streamlined authority required listing for the treatment of hypercalcaemia of malignancy on a cost minimisation basis to pamidronate . In November 2021, this recommendation for bisphosphonate-refractory hypercalcaemia of malignancy was withdrawn by the PBAC with the support from the sponsor . In December 2024, Xgeva denosumab 120 mg/mL solution for injection pre-filled syringe with automatic needle guard was first listed on the ARTG .