Xgeva - denosumab

What is Xgeva - denosumab?

Xgeva is a solution for injection containing the active substance denosumab. It is available in single-use vials containing 120 mg of denosumab.

What is Xgeva - denosumab used for?

Xgeva is used to prevent complications of the skeletal system in adults with widespread solid bone tumors. Such complications include fractures, spinal cord compression (situation in which the bone compresses the spinal cord) or complications that make radiotherapy or surgery necessary.

The medicine can only be obtained with a prescription.

How is Xgeva - denosumab used?

Xgeva is given once every four weeks by single subcutaneous injection (120 mg) in the thigh, abdomen or upper arm. Patients must receive calcium and vitamin D supplementation during treatment with Xgeva.

How does Xgeva - denosumab work?

The active substance in Xgeva, denosumab, is a monoclonal antibody. A monoclonal antibody is an antibody (a type of protein) developed to recognize and bind to a specific structure (the antigen) present in the body. Denosumab has been designed to bind to an antigen called RANKL implicated in the activation of osteoclasts, the body's cells responsible for the degradation of bone tissue. By binding to the antigen and inhibiting its action, denosumab reduces the formation and activity of osteoclasts. This in turn limits the loss of bone substance, making fracture episodes and other serious complications affecting the skeletal system less likely.

How has Xgeva - denosumab been studied?

The effects of Xgeva were first tested in experimental models before being studied in humans.

Xgeva was compared with zoledronic acid (another medicine used to prevent complications of the skeletal system) in three important studies conducted on patients with bone metastases due to different tumor types. The first study involved 2 046 patients with breast cancer. The second study was conducted on 1 901 men with prostate cancer who had not responded to hormone therapy. The third study involved 1, 776 patients with advanced solid-state tumors in various parts of the body, with the exception of breast and prostate, or with multiple myeloma (a bone marrow tumor).

All the studies examined the risk of the onset of a first "event involving the skeletal system" (such as a fracture, a spinal cord compression or an episode that required radiotherapy or surgery) during the study period, measuring the time interval elapsed until the occurrence of this event.

What benefit has Xgeva - denosumab shown during the studies?

Xgeva has been shown to be effective in delaying a first event in the skeletal system in subjects involved in the studies. In the first and second studies, Xgeva reduced the risk of developing a first event of this kind by 18% compared to zoledronic acid. In the third study the reduction of this risk was 16% compared to zoledronic acid.

What is the risk associated with Xgeva - denosumab?

The most common side effects with Xgeva (seen in more than 1 patient in 10) are dyspnoea (difficulty breathing) and diarrhea. For the full list of all side effects reported with Xgeva, see the Package Leaflet.

Xgeva should not be used in people who may be hypersensitive (allergic) to denosumab or any of the other substances. It must also not be used in patients with hypocalcemia (lower than normal blood calcium levels) severe, untreated.

Why has Xgeva - denosumab been approved?

The CHMP noted that new effective treatment of skeletal diseases associated with advanced stage cancers is needed, especially in patients with kidney problems, because currently available therapies may be kidney toxic. The Committee considered that the effectiveness of Xgeva in the prevention of events affecting the skeletal system has been demonstrated and that the medicine is less toxic to the kidneys and easier to administer than other treatments. However, in multiple myeloma, overall survival and disease progression rates (the time before a worsening of the disease) were recorded were worse in patients treated with Xgeva than in subjects treated with zoledronic acid; therefore the committee decided that the risks of the medicine outweigh the benefits for this group of patients. The CHMP decided that Xgeva's benefits are greater than its risks in patients with solid tumors and recommended that it be given marketing authorization.