Aredia has been approved for treatment of osteolytic bone metastases of breast cancer, in conjunction with standard antineoplastic therapy. Aredia is the first drug that has been proven to reduce the incidence of skeletal complications of metastatic breast cancer, thereby reducing the need for radiation therapy or surgery to the bone. It has also been shown to provide relief of bone pain caused by metastatic breast cancer, thereby reducing the need for narcotic analgesics. The drug is also indicated for the treatment of osteolytic bone lesions of multiple myeloma, moderate-to-severe hypercalcemia of malignancy, and moderate-to-severe Paget's disease.

The marketing clearance was based upon data from two large, placebo-controlled, double-blind, multicenter studies in breast cancer subjects with osteolytic bone metastases. These studies enrolled 372 subjects treated with hormonal therapy and 382 subjects treated with chemotherapy. All subjects enrolled had stage IV breast cancer with two or more lytic lesions, with at least one lesion that was one centimeter or greater in diameter. Subjects were randomized to receive Aredia 90 mg every three to four weeks via two-hour IV infusions for 12 months or matching placebo, in conjunction with either hormonal therapy or chemotherapy. The studies demonstrated that patients receiving Aredia had a significant reduction in skeletal complications, the primary endpoint, and significant relief of bone pain, a secondary endpoint. The Aredia treatment effect appeared to be less pronounced in the study of those receiving chemotherapy. Additionally, subjects receiving Aredia had fewer pathologic fractures and a decreased need for radiation therapy for pain or skeletal complications.

In these studies, skeletal morbidity was defined as the mean number of skeletal complications (pathologic fractures, spinal cord compression, radiation therapy, or surgery to bone) per subject per year. In subjects receiving concomitant chemotherapy, Aredia provided a 36% reduction in the skeletal morbidity rate (2.1 vs. 3.3 with placebo). In subjects receiving concomitant hormonal therapy, skeletal morbidity was reduced by 31% with Aredia (2.4 vs. 3.5). For an average subject, these reductions mean one fewer major skeletal complication per year with Aredia.

Additional results of the trials show that subjects treated with Aredia had fewer skeletal complications than those subjects who received placebo. Also, fewer Aredia-treated subjects required radiation therapy for pain, or to prevent or treat fractures, compared to subjects treated with placebo. Among subjects who had pain at the beginning of the trials, Ardia-treated subjects had less severe pain, and experienced pain less often, in comparison to subjects who did not receive Aredia. Additionally, Aredia-treated subjects also had a decreased need for strong pain medication, unlike subjects receiving placebo. The statistical significance of these results may be overstated due to numerous analyses.

The incidence and type of adverse events with Aredia were similar to those with placebo, with most events likely due to the underlying disease or concomitant antineoplastic therapy. The most frequent adverse events were fatigue, fever, nausea, vomiting, anemia, and skeletal pain. Transient arthralgias and myalgias were reported slightly more frequently with Aredia than with antineoplastic therapy alone (12% and 23% vs. 8% and 17%, respectively). Serum calcium and electrolytes must be closely monitored, as must subjects with preexisting anemia, leukopenia, or thrombocytopenia.

Breast cancer is diagnosed in approximately 184,000 women each year, and has the highest incidence of associated metastatic bone disease among all cancers. Approximately 100,000 breast cancer subjects are currently living with cancer that has metastasized to the bone. Subjects with osteolytic bone metastases often suffer from skeletal complications including pathologic bone fractures, spinal cord compression, impaired mobility, and chronic and debilitating bone pain.