Positive Results for Bone Drug in Multiple Myeloma

Amgen announces top-line results from trial evaluating Xgeva in multiple myeloma.

Amgen recently announced positive results from a phase 3 clinical trial of Xgeva (denosumab) in patients with multiple myeloma. Xgeva targets the RANK ligand pathways to prevent the creation, function, and survival of osteoclasts, which are linked to bone deterioration.

Xgeva met the primary study endpoint of non-inferiority (hazard ration= 0.98, 95% CI, 0.85 — 1.14) to zoledronic acid in delaying the onset of first skeletal-related event in these patients. However, secondary endpoints of delaying time to first skeletal-related event and delaying time to first- and subsequent skeletal-related events were not met, according to a press release from Amgen.

Included in the ‘482 study (NCT01345019) were 1718 patients newly diagnosed with multiple myeloma. Patients were randomized 1:1 to receive subcutaneous Xgeva 120-mg and intravenous placebo, or intravenous zoledronic acid 4-mg and subcutaneous placebo. Patients received treatment once every 4 weeks.

Reduction in skeletal-related events, such as fractures, radiation to bone, surgery to bone, or spinal cord compression was seen in the group treated with Xgeva, demonstrating non-inferiority to zoledronic acid. Adverse events associated with the drug were consistent with its known safety profile. Common adverse events included diarrhea and nausea.

Xgeva has received FDA approval for the prevention of skeletal-related events in patients with bone metastases from solid tumors, Amgen reported. It is also indicated for adult patients with giant cell tumor of the bone that is unable to be surgically removed.

The FDA has also approved this treatment in patients with hypercalcemia of malignancy refractory to bisphosphate therapy. The drug is additionally marketed as Prolia for other indications, according to Amgen.

These findings could lead to a new treatment option for the 114,000 patients diagnosed with multiple myeloma annually. More than 800,000 patients with this incurable cancer die each year.

Bone lesions are characteristic of multiple myeloma, and can cause an increased risk of bone complications, with approximately 75% of these patients receiving treatment for the complications. Prevention of bone complications is a crucial aspect of multiple myeloma treatment since skeletal-related events can cause significant morbidity, according to the press release.

“Bone complications like fracture, spinal cord compression and radiation or surgery to bone are devastating for multiple myeloma patients. Many of these patients suffer from renal impairment, which has limited their treatment options," said Sean E. Harper, MD, executive vice president of Research and Development at Amgen. "Xgeva's unique mechanism of action has the potential to prevent bone complications in multiple myeloma patients regardless of their renal status, fulfilling an important unmet medical need."