Amgen submitted a supplemental Biologics Licence Application (sBLA) to the U.S. Food and Drug Administration (FDA) seeking to expand the indication of Xgeva (denosumab) to patients with multiple myeloma.
Xgeva is used to prevent skeletal-related events (SREs), including fractures, spinal cord compression, or the need for surgery or radiation treatments in the bone, in patients whose solid tumors have spread to the bone.
Multiple myeloma is often characterized by bone lesions, which affect more than 90 percent of patients. But in the United States, Xgeva is not approved for the treatment of SREs in myeloma patients.
“Bone lesions are a hallmark of multiple myeloma and often result in bone complications, which can be devastating for patients,” Sean E. Harper, MD, executive vice president of Research and Development at Amgen, said in a press release. “Current treatment options for bone complications are limited to bisphosphonates, which are associated with renal toxicity. Approximately 60 percent of all multiple myeloma patients have or will develop renal impairment over the course of the disease.”
“Xgeva’s unique mechanism of action may offer multiple myeloma patients a novel treatment option that is not renally cleared,” Harper added, saying the company looks forward to collaborating with the FDA to make the drug available to these patients.
The recent application is based on data from the pivotal Phase 3 trial (NCT01345019), an international, double-blind study that assessed the safety and effectiveness of Xgeva vs. Zometa (zoledronic acid) in the prevention of SREs in newly diagnosed myeloma patients with bone lesions. Zometa is the standard biphosphonate given to myeloma patients with bone problems.
A total of 1,718 patients were randomized to receive either subcutaneous Xgeva and intravenous placebo, or intravenous Zometa plus subcutaneous placebo, every four weeks.
The study’s primary endpoint was the non-inferiority of Xgeva in the time to the first on-study SRE; secondary outcomes included superiority of Xgeva in time to first-and-subsequent SRE, and time to first on-study SRE. SREs included pathologic fracture, radiation to bone, surgery to bone, or spinal cord compression.
Data revealed in October 2016 showed that the trial met its primary endpoint of non-inferiority in delaying the time to first on-study SRE, but failed to meet the two secondary objectives.
Xgeva showed a tendency for better overall survival, but the results were not statistically significant. Median progression-free survival, however, was significantly better in the Xgeva arm, with time to disease progression or death being 10.7 months higher than in those receiving Zometa.
Side effects from Xgeva were consistent with those seen in past clinical studies in other indications. Still, the most common side effects, diarrhea and nausea, had similar incidence on both study arms.
The findings were recently presented at the 16th International Myeloma Workshop March 1-4 in New Delhi, India.