FDA Approves Denosumab for New Indication

The FDA approved denosumab for the treatment of hypercalcemia of malignancy (HCM) refractory to bisphosphonate therapy.

Denosumab, manufactured by Amgen, is approved for subcutaneous injection 120 mg every 4 week with additional doses of 120 mg on days 8 and 15 in the first

HCM is a serious complication of advanced cancer. It occurs most often in patients with squamous cell cancer (eg, lung cancer, head and neck cancer), breast cancer, kidney cancer, myeloma, and lymphoma. An estimated 2.7% of US patients with cancer developed HCM, according to 2012 data. If left untreated, HCM can lead to renal failure, progressive mental impairment, coma, and death.

The FDA approval of denosumab for HCM was based on results from an open-label, single-group study of patients with advanced cancer and persistent HCM after recent bisphosphonate treatment.

The primary end point was the proportion of patients with a response, defined as an albumin-corrected serum calcium level of ≤11.5 mg/dL (2.9 mmol/L) within 10 days after the first dose of denosumab, according to a statement from Amgen.

The study achieved its primary end point with a response rate at day 10 of 63.6% in the 33 patients evaluated. The estimated median time to response was 9 days, and the median duration of response was 104 days.

The most common adverse events associated with denosumba included nausea, dyspnea, decreased appetite, headache, peripheral edema, vomiting, anemia, constipation, and diarrhea.

Denosumab is a fully human monoclonal antibody that targets the receptor activator of the nuclear factor-kappa-B ligand protein that contributes to bone maintenance.

Denosumab was first previously FDA-approved in June 2010 for the treatment of osteoporosis and later approved for use in preventing skeletal-related events in adults with solid tumors and bone metastases. In 2013, the drug received FDA approval for adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity.—Kerri Fitzgerald