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.
In 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.
Denosumab was 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 metastases.
Xgeva is marketed by
Thousand Oaks, Calif.-based Amgen.