XGEVAÂ® (Denosumab) Granted Marketing Authorization in the European Union
THOUSAND OAKS, Calif., July 15, 2011 /PRNewswire/ — Amgen (NASDAQ: AMGN) today announced that the European Commission (EC) has granted marketing authorization for XGEVAÃ‚® (denosumab) for the prevention of skeletal-related events (SREs) (pathological fracture, radiation to bone, spinal cord compression or surgery to bone) in adults with bone metastases from solid tumors. This approval of XGEVA applies to all 27 European Union (EU) member states. The EC also granted XGEVA an additional year of data and market exclusivity in the EU since the indication was considered new for denosumab and based on the significant clinical benefit of XGEVA in comparison with existing therapies.
Bone metastases, the spread of cancer to the bones, are a common and serious concern for patients with advanced cancer and present a burden to the healthcare system. Weakened bones due to metastases can lead to SREs. The primary goal of treatment for bone metastases is to prevent the occurrence of these debilitating and costly SREs.
“Skeletal-related events associated with bone metastases are truly devastating and painful for patients living with cancer, and today’s approval of XGEVA marks a real advance,” said Professor Ingo J. Diel, M.D., Institute for Gynecological Oncology, SPGO, Mannheim, Germany. “In clinical trials XGEVA demonstrated sustained protection from SREs and also delayed the progression of pain. These factors will make a genuine difference in the lives of patients living with advanced cancer.”
The marketing authorization for XGEVA is based on three pivotal, Phase 3 head-to-head trials that evaluated the effectiveness of XGEVA versus zoledronic acid at delaying SREs. The SRE clinical program for XGEVA spanned more than 50 tumor types in over 5,700 patients. In the SRE trials, XGEVA demonstrated a clinically meaningful improvement in preventing SREs compared to zoledronic acid. In these trials, XGEVA was administered every four weeks as a 120 mg subcutaneous injection, versus zoledronic acid delivered every four weeks via a 15-minute intravenous infusion, with adjustments for kidney function per the requirements of the zoledronic acid prescribing information.
In patients with breast or prostate cancer and bone metastases, XGEVA was superior to zoledronic acid in reducing the risk of SREs. In patients with bone metastases due to other solid tumors or multiple myeloma, XGEVA was non-inferior to zoledronic acid in reducing the risk of SREs. In an integrated analysis of all three studies XGEVA was superior to zoledronic acid in delaying time to first on-study SRE by 17 percent or 8.2 months (median time to first skeletal related event of 27.6 months for XGEVA and 19.4 months for zoledronic acid, (p<0.0001)). In this analysis, XGEVA was also superior to zoledronic acid in delaying time to first-and-subsequent on-study SRE by 18 percent (p<0.0001).
In patients with mild or no pain at baseline, time to worsening pain was delayed for XGEVA compared to zoledronic acid (198 versus 143 days) (p=0.0002). The time to pain improvement was similar for XGEVA and zoledronic acid in each study and the integrated analysis.
Overall rates of adverse events and serious adverse events were generally similar between XGEVA and zoledronic acid. Osteonecrosis of the jaw (ONJ) was seen in approximately 1-2 percent of patients, with no statistically significant difference between treatment arms. Hypocalcemia was more frequent in the XGEVA treatment group. Overall survival and progression-free survival were similar between arms in all three trials.
“Today’s approval of XGEVA marks the culmination of many years of research and innovation by Amgen scientists, beginning with the discovery of the RANK Ligand pathway and the understanding of its role in bone biology to the development of the denosumab oncology clinical program,” said Willard H. Dere, M.D., senior vice president and international chief medical officer at Amgen. “XGEVA promises to make a real difference for patients with cancer whose daily lives are affected by the consequences of bone metastases.”
XGEVA is the first and only RANK Ligand inhibitor approved in the EU 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. XGEVA is the first novel bone metastases treatment for advanced cancer patients in more than a decade.
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 delivered as an every four week 120 mg subcutaneous injection and is not associated with renal toxicity or acute phase reactions.
XGEVA Regulatory Status
XGEVA is currently approved in the United States (U.S.) for the prevention of SREs in patients with bone metastases from solid tumors. XGEVA was approved following a six month priority review by the U.S. Food and Drug Administration (FDA). In the U.S., XGEVA is not indicated for the prevention of SREs in patients with multiple myeloma.(i) XGEVA is also approved in Canada for reducing the risk of developing SREs in patients with bone metastases from breast cancer, prostate cancer, non-small cell lung cancer, and other solid tumors. In Canada, XGEVA is not indicated for reducing the risk of developing SREs in patients with multiple myeloma.(ii)
Amgen has also submitted marketing applications for XGEVA in Australia, Mexico, Russia and Switzerland. In Japan, Amgen is working with its licensing partner, Daiichi-Sankyo Company, Limited and a marketing application was submitted in August 2010. 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 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.
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.
Bone Metastases and SREs: Prevalence and Impact
Bone metastases occur in more than 1.5 million patients with cancer worldwide and are most commonly associated with cancers of the prostate, lung and breast, with incidence rates as high as 90 percent of patients with metastatic disease. (iii), (iv), (v), (vi)
Approximately 50-70 percent of cancer patients with bone metastases will experience debilitating SREs. (vii), (viii), (ix) Events considered to be SREs include fractures, spinal cord compression and severe bone pain that may require surgery or radiation.(x) Such events can profoundly disrupt a patient’s life and can cause disability and pain. (xi), (xii), (xiii)
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(i) XGEVA(TM) (denosumab) [prescribing information]. Thousand Oaks, Calif: Amgen; 2010.
(ii) XGEVA(TM) Product Monograph. Amgen Canada Inc. May 2011
(iii) Tannock IF, Wit R, Berry WR, Horti J, Pluzanska A, Chi K, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351(15):1502-12.
(iv) Petrylak DP, Tangen CM, Hussain MH, Lara PN, Jones JA, Taplin ME, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004;351(15):1513-1520.
(v) Prostate cancer clinical trial end points: ”RECIST”ing a step backwards. American Association for Cancer Research website. clincancerres.aacrjournals.org. Accessed on February 16, 2011.
(vi) Coleman RE. Skeletal complications of malignancy. Cancer. 1997; 80(suppl): 1588-1594.
(vii) Lipton A, Theriault RL, Hortobagyi GN. Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases. Cancer. 2000;88:1082-1090.
(viii) Saad F, Lipton A, Cook R, Chen YM, Smith M, Coleman R. Pathologic fractures correlated with reduced survival in patients with malignant bone disease. Cancer. 2007;110:1860-1867.
(ix) Rosen LS, Gordon D, Tchekmedyian NS, et al. Nonsmall cell lung carcinoma and other solid tumors. Cancer. 2004;100:2613-2621.
(x) Costa L, Badia X, Chow E, Lipton A, Wardley A. Impact of skeletal complications on patients’ quality of life, mobility, and functional independence. Support Care Cancer. 2008; 16: 879-889.
(xi) Norgaard M, Jensen AO, Jacobsen JB, Cetin K, Fryzek JP, Sorensen HT. Skeletal related events, bone metastasis and survival of prostate cancer: a population based cohort study in Denmark (1999 to 2007).J Urol. 2010; 184:162-167.
(xii) Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos In.t 2006;17:1726-1733.
(xiii) Saad F, Gleason DM, Murray R, et al. A Randomized, Placebo-Controlled Trial of Zoledronic Acid in Patients With Hormone-Refractory MetastaticProstate Carcinoma. Journal Ntl Cancer Inst. 2002;19:1458-1468.