Amgen's application for expanded indications for denosumab (Xgeva) were turned down by the FDA (Food and Drug Administration) - the expanded indications were to include bone metastases prevention in patients with castration-resistant prostate cancer. The FDA told Amgen in a CRL (Complete Response Letter) that evidence regarding better bone metastasis-free survival was "insufficient", and as such, the potential adverse effects of osteonecrosis of the jaw, among others were not so far compellingly outweighed by the benefits.
Earlier on this year, an FDA Advisory Committee (Oncologic Drugs Advisory Committee) voted that the expanded indication should not go ahead - mainly because of the risk of osteonecrosis.
Osteonecrosis of the jaw or ONJ is when the jaw bone is exposed and suffers from the consequences of not enough blood supply. The bone starts to weaken and dies, which frequently causes severe pain. ONJ is linked to cancer therapies, steroid use, infection, and some other treatments.
Xgeva is already approved for patients with solid tumors, to prevent skeletal-related events, including those with prostate cancer. Patients with multiple myeloma whose malignancy has metastasized are excluded from the current indication.
According to Amgen, Xgeva is the first new bone metastases therapy for patients with advanced cancer in nearly ten years. It is administered every four weeks via subcutaneous injection, in doses of 120 mg.
In a communiqué today, Amgen wrote:
XGEVA is a fully human monoclonal antibody that binds to RANK Ligand, a protein essential for the formation, function and survival of osteoclasts (the cells that break down bone). XGEVA prevents RANK Ligand from activating its receptor, RANK, on the surface of osteoclasts, thereby decreasing bone destruction.
Sean E. Harper, M.D., executive vice president of Research and Development at Amgen, said:
"We are reviewing the complete response letter and will work with FDA to determine any next steps.
The FDA's action today does not impact the approved indication of XGEVA in the prevention of skeletal-related events in men with bone metastases from prostate cancer, which was acknowledged by the FDA and the advisory committee members who discussed the application."
Written by Christian Nordqvist