Xgeva (denosumab) was approved by the U.S. Food and Drug Administration (FDA) to treat bone problems (skeletal-related events) in multiple myeloma (MM) patients.

Developed and marketed by Amgen, it is designed to prevent fractures, spinal cord compressions, or the need for radiation therapy or surgery to the bones of MM patients.

How Xvega works

Xvega is an antibody that binds to and blocks the activity of bone cells called osteoclasts, which play a role in breaking down bone tissue and are overactive in muliple myeloma by the nature of this disease of the bone marrow. Specifically, it works by blocking the activity of the RANK ligand (RANKL), a protein essential for osteoclast formation, function and survival, to protect patients’ bones.

Because Xgeva is not cleared through the kidneys, it could be a new treatment option for patients with kidney insufficiency or kidney failure. Kidney problems, including kidney failure, are common complications of MM, with some estimates placing them as affecting 60 percent of all multiple myeloma patients. Existing treatments can also be toxic to kidneys.

Xgeva in clinical trials

Two clinical trials testing Xvega in multiple myeloma patients have been completed. A Phase 3 study (NCT01345019) was pivotal in the FDA’s decision to approve the treatment for MM; it was approved earlier to treat bone metastases in solid cancers. This study included 1,718 patients and compared the effect of Xgeva to zoledronic acid (brand names, Reclast and Zometa). Xgeva was found to be at least as effective (non-inferior; the trial’s main outcome) as zoledronic acid in preventing skeletal lesions. Moreover, progression-free survival was in a range of 10.7 months higher in the Xgeva-treated patient group than in the zoledronic acid-treated group.

An earlier Phase 2 proof-of-concept trial (NCT00259740) investigated denosumab in MM patients whose cancer was continuing to progress or at a plateau, by evaluating changes in M-protein levels in their blood while under treatment. M-proteins, produced by this cancer’s cells, are present at high levels in patients’ blood and serve as disease markers. Stable disease for up to 16.5 months was seen in 11 newly relapsed patients (21 percent; their cancer returned within three months prior to study start). A total of 19 (46 percent) participants with stable myeloma remained stable for up to 18.3 months, and a majority reported maintained or improved pain levels, according to a 2009 published study of this trial.

A new Phase 2 trial (NCT02833610) that began in 2016 is studying the safety and tolerability of Xvega in about 55 MM patients with kidney insufficiency. Its main goal, or endpoint, is percentage change in levels of serum C-terminal telopeptide of type 1 collagen (sCTX), a marker of bone turnover. The trial, which concludes in 2023, is recruiting participants in Massachusetts and Ohio. More information can be obtained by cliquing on the trial’s identification number.

Other information

The most common side effects associated with the Xgeva use are diarrhea, nausea, a low red blood cell count, low blood platelets and calcium levels, back pain, swelling of the lower legs or hands, upper respiratory tract infection, rash, and headache. The most common serious adverse reaction is pneumonia.

Xgeva is also used to treat bone metastasis in solid tumors, including breast, prostate and lung cancers. It is also approved in the U.S. to treat hypercalcemia of malignancy resistant to bisphosphonate therapy, a rare but serious complication of advanced cancer due to bone resorption.

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