The U.S. Food and Drug Administration approved Xgeva (denosumab) on Thursday to help prevent
skeletal-related events (SREs) in patients with cancer that has spread (metastasized) and damaged
the bone. Skeletal-related events include bone fractures from cancer and bone pain requiring
Xgeva is a monoclonal antibody that targets a protein involved in
cancer-related bone destruction called human RANKL. Other FDA-approved drugs for similar conditions
include Zometa (zoledronic acid) and Aredia (pamidronate disodium).
Xgeva is not
approved for patients with multiple myeloma or other cancers of the blood.
metastases represent a major cause of pain and suffering in patients with cancer and can affect a
patient’s quality of life,” said Richard Pazdur, M.D., director of the Office of
Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research. “Xgeva has
a different mechanism of action than currently approved drugs aimed at reducing bone complications
Xgeva’s safety and effectiveness were confirmed in three
randomized, double-blind clinical studies in 5,723 patients comparing Xgeva with Zometa. One study
involved patients with breast cancer, another in patients with prostate cancer, and a third
included patients with a variety of other cancers.
The studies were designed to
measure the time until occurrence of a fracture or spinal cord compression due to cancer or until
radiation or surgery for control of bone pain was needed.
In patients with breast or
prostate cancers, Xgeva was superior to Zometa in delaying SREs. In men with prostate cancer, the
median time to an SRE was 21 months with Xgeva compared to 17 months with Zometa.
patients with breast cancer, the median time to an SRE was 26 months with Zometa and has not yet
been reached with Xgeva. In patients with other solid tumors, time to development of an SRE was
similar for both Xgeva and Zometa. The most common solid tumors were non-small cell lung cancer,
multiple myeloma, kidney (renal) cancer, and small cell lung cancer.
The most serious
side effects experienced with Xgeva were low calcium levels in the blood (hypocalcemia), and
osteonecrosis of the jaw, a severe disease resulting from reduced blood flow to areas of the jaw
and exposed jaw bone, causing pain, swelling, numbness, or infection.
originally approved under another trade name, Prolia, in June 2010. Prolia is indicated to treat
postmenopausal women with osteoporosis who are at high risk for bone fractures. Xgeva is
administered using a higher dose and with more frequent dosing than Prolia. Denosumab has a
different safety profile in patients with osteoporosis than in patients with cancer and bone
Xgeva is marketed by Thousand Oaks, Calif.-based Amgen.