Xgeva (denosumab) has been approved by the U.S. FDA for the treatment of GCTB (giant cell tumor of the bone) in adults and skeletally mature adolescents. GCTB is a rare tumor which is usually non-cancerous.

Giant cell tumor of the bone typically affects adults aged between 20 and 40 years. In the majority of cases, GCTB remains localized (does not spread). However, as it grows it destroys normal bone, resulting in severe pain, bone fractures and a limited range of motion.

GCTB can become malignant and spread to the lungs, however this is rare.

Denosumab is a monoclonal antibody that binds to the protein, RANKL, that is essential for the maintenance of healthy bone.

The FDA stated that Xgeva has been approved for patients with unresectable GCTB, meaning the tumor cannot be removed surgically, or when surgery is not recommended because of a risk of severe morbidity, such as joint removal or loss of limbs. If left untreated, GCTB commonly results in the total destruction of the affected bone, leading to bone fracture, joint dysfunction, deformity or amputation.

Xgeva should only be used in patients whose bones have matured.

Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research, said:

“Today’s approval of Xgeva provides a needed treatment option for patients with GCTB who are not surgical candidates or who would otherwise have to undergo extensive, life-altering surgery.”

Xgeva was evaluated under the FDA’s priority review program, which provides for an accelerated review of medications that offer major advances in treatment, or provide a therapy where no adequate treatment exists. Xgeva, being a drug for the treatment of a rare disease, was granted orphan product designation.

During the approval process, FDA experts examined data from two clinical trials involving 305 patients (adults and adolescents). They had all been diagnosed with GCTB that were recurrent, inoperable, or where there was a serious risk of severe morbidity following surgery.

The tumors could be measured in 187 of the 305 patients. Forty-seven of them experienced a reduction in tumor size after three months on Xgeva. During a 20-month follow-up period, regrowth occurred in three patients whose tumors had shrunk during treatment.

The most common side effects associated with Xgeva treatment included arthralgia (joint pain), fatigue, headache, back pain, extremity pain and nausea. The most serious side effects included inflammation/infection of the bone (osteomyelitis) and osteonecrosis (areas of dead bone).

As Xgeva may harm the fetus, females of reproductive age should use highly effective contraception.

In 2010, the FDA approved Xgeva for the prevention of fractures when cancer has spread to the bones.

Xgeva is marketed by Amgen.

Sean E. Harper, M.D., executive vice president of Research and Development at Amgen, said:

“With today’s XGEVA FDA approval, Amgen can offer a much needed treatment option to patients who suffer from giant cell tumor of bone that cannot be adequately treated with surgery. Advances in our understanding of the underlying biology of this rare disorder have allowed Amgen to generate compelling clinical evidence to address the medical needs of patients and their healthcare providers.”

Written by Christian Nordqvist