THOUSAND OAKS, Calif., Nov. 15, 2011 /PRNewswire via COMTEX/ --
Amgen (NASDAQ: AMGN) announced today the publication of results from a Phase 3 trial (the '147 study) that evaluated XGEVA® (denosumab) for use in preventing or delaying the onset of bone metastases in men with nonmetastatic castration-resistant prostate cancer (CRPC). Published in The Lancet, the study found XGEVA significantly prolonged bone metastasis-free survival, delayed time to bone metastasis and reduced the risk of symptomatic bone metastases. This study is the first to demonstrate that targeting the bone microenvironment prevents bone metastasis in men with prostate cancer.
"The prevention of bone metastases is a major unmet medical need for men with castration-resistant prostate cancer. Bone metastases are a significant concern for these patients who have historically had poor outcomes," Matthew Smith, M.D., Ph.D., professor of medicine and the director of Genitourinary Oncology at Massachusetts General Hospital Cancer Center. "The more than four-month increase in bone metastasis-free survival with XGEVA treatment is a clinically significant finding that has the potential to improve the management of men living with prostate cancer."
Based on the results of this study, Amgen filed a supplemental Biologics License Application (sBLA) to expand the indication for XGEVA to treat men with CRPC to reduce the risk of developing bone metastases. The U.S. Food and Drug Administration (FDA) has set April 26, 2012 as the targeted Prescription Drug User Fee Act (PDUFA) action date for the sBLA. If approved, XGEVA would be the first-and-only therapy licensed to prevent or delay the spread of cancer to the bone.
In the '147 study, XGEVA significantly improved median bone metastasis-free survival by 4.2 months, a risk reduction of 15 percent, compared with placebo (29.5 versus 25.2 months, respectively; hazard ratio (HR) 0.85; 95 percent CI: 0.73, 0.98; p=0.028). XGEVA significantly delayed the time to first bone metastases by 3.7 months compared with placebo (HR 0.84; 95 percent CI: 0.71, 0.98; p=0.032; risk reduction of 16 percent). XGEVA also reduced the risk of bone metastases that were symptomatic by 33 percent (HR 0.67; 95 percent CI: 0.49, 0.92; p=0.01). Overall survival was similar between groups (HR 1.01; 95 percent CI: 0.85, 1.20; p=0.91). The study design required that patients discontinue XGEVA following development of bone metastasis so that they could receive standard approved treatment for prevention of skeletal-related events (SREs), therefore, the potential to measure a positive impact on survival was limited.
In the '147 trial, adverse events and serious adverse events were relatively similar between the XGEVA and placebo arms. Hypocalcemia and osteonecrosis of the jaw (ONJ) were reported with increased frequencies in the XGEVA treated patients. The yearly rate of ONJ in the XGEVA arm was similar to prior XGEVA trial results. Back pain was the most common adverse event reported in the XGEVA arm of the trial.
Study '147 was a randomized, placebo-controlled, multicenter Phase 3 study comparing the treatment effect of XGEVA to placebo in prolonging bone metastasis-free survival - a measure of the time that patients live without progressing to bone metastases - in 1,432 men with hormone-refractory (castration-resistant) prostate cancer who had no bone metastases at baseline but were at increased risk of developing them based on their prostate specific antigen (PSA) criteria. The primary endpoint of the trial was time to first occurrence of bone metastases or death from any cause with secondary endpoints including time to first occurrence of bone metastases (excluding death) and overall survival.
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. XGEVA is the first novel bone metastases treatment for advanced cancer patients in nearly a decade. XGEVA is delivered as an every four week 120 mg subcutaneous injection and does not require dose adjustment regardless of renal function.
XGEVA is the first-and-only RANK Ligand inhibitor approved by the FDA indicated for the prevention of SREs in patients with bone metastases from solid tumors. XGEVA was approved following a six month priority review by the FDA. XGEVA is not indicated for the prevention of SREs in patients with multiple myeloma.
The European Commission (EC) granted a Marketing Authorization for XGEVA for the prevention of SREs (pathological fracture, radiation to bone, spinal cord compression or surgery to bone) in adults with bone metastases from solid tumors. As part of the review, the EC also granted XGEVA one additional year of marketing protection based on the indication being considered new for denosumab and the significant clinical benefit offered by the product in comparison with existing therapies. XGEVA also has similar indications to prevent SREs in Canada and Australia.
Amgen has also submitted marketing applications for XGEVA in Mexico, Russia and Switzerland. In Japan, Amgen is working with its licensing partner, Daiichi Sankyo Company, Limited and a marketing application was submitted. In addition,Amgen and GlaxoSmithKline (GSK) have a collaboration agreement for the commercialization of XGEVA in a number of countries where Amgen does not currently have a commercial presence. In these countries, marketing applications are filed by GSK.
XGEVA has been studied in over 7,000 patients with cancer. In clinical trials, XGEVA demonstrated a clinically meaningful improvement compared to the standard of care in preventing bone complications. XGEVA is also being investigated for the potential use to delay the onset of bone metastasis in adjuvant breast cancer.
For more information on XGEVA, please visit http://www.xgeva.com/.
XGEVA Important Safety Information
XGEVA can cause severe hypocalcemia. Correct pre-existing hypocalcemia prior to XGEVA treatment. Monitor calcium levels in patients at greater risk of developing hypocalcemia. Administer calcium and vitamin D in all patients (unless hypercalcemia is present). Advise patients to contact a healthcare professional for symptoms of hypocalcemia.
Osteonecrosis of the jaw (ONJ) can occur in patients receiving XGEVA. Patients who are suspected of having or who develop ONJ while on XGEVA should receive care by a dentist or an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition.
Adverse reactions in patients receiving XGEVA included fatigue/asthenia, hypophosphatemia, nausea, dyspnea and diarrhea.
Please visit http://www.amgen.com/ for full U.S. prescribing information.
Amgen discovers, develops, manufactures and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science's promise by bringing safe and effective medicines from lab, to manufacturing plant, to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis, bone disease and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people's lives. To learn more about our pioneering science and our vital medicines, visit http://www.amgen.com/. Follow us on www.twitter.com/amgen.
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