FDA Expands Denosumab for Giant Cell Tumor of Bone

Nick Mulcahy


June 13, 2013

The US Food and Drug Administration (FDA) today expanded the approved use of denosumab (Xgeva, Amgen) to include the treatment of adults and some adolescents with giant cell tumor of the bone (GCTB), a rare condition that is usually noncancerous.

Denosumab is intended for use in adults when GCTB is unresectable or when surgery is likely to result in severe morbidity. It is only indicated for adolescents whose bones have matured.

The drug becomes the first systemic therapy for this condition, which typically does not metastasize but causes pain, limited range of motion, and bone fractures. Only rarely does GCTB transform into a cancerous tumor, which in turn can spread to the lungs.

Denosumab, which was first approved by the FDA in June 2010 for the treatment of osteoporosis, was approved later that year for use in preventing skeletal-related events in adults with solid tumors and bone metastases. It is also approved in Europe for the same use.

Denosumab is a fully human monoclonal antibody that targets the receptor activator of the nuclear factor-kappa-B ligand (RANKL) protein, which contributes to bone maintenance. That protein is present in GCTB.

News of the drug's promise in GCTB was widely covered in 2010.

"Today's approval of denosumab 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," said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products at the FDA Center for Drug Evaluation and Research, in a press statement.

Of 305 adult or adolescent patients in clinical trials, 187 had measurable tumors, 47 of whom had a reduction in tumor size after an average of 3 months. Only 3 of the responding patients had regrowth of GCTB during follow-up (median duration, 20 months).

All the clinical trial participants had confirmed cases of GCTB that were recurrent, unresectable, or vulnerable to severe morbidity upon surgery.

The common adverse effects of denosumab reported in the clinical trials include arthralgia, headache, nausea, fatigue, back pain, and extremity pain. The most common serious adverse effects were osteonecrosis of the jaw and osteomyelitis. The FDA notes that women of reproductive potential should use highly effective contraception while taking denosumab because of potential fetal harm.

The FDA reviewed denosumab as an orphan product under its priority review program.

"Advances in our understanding of the underlying biology of this rare disorder have allowed Amgen to generate compelling clinical evidence to address the medical need of patients and their healthcare providers," said Sean E. Harper, MD, executive vice president of research and development at Amgen, in a press statement.


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