FDA Approves Xgeva

FDA Approves Amgen's Xgeva (denosumab) for the Prevention of Skeletal-Related Events in Patients with Bone Metastases from Solid Tumors

THOUSAND OAKS, Calif., Nov. 18, 2010 /PRNewswire-FirstCall/ -- Amgen Inc. today announced that the U.S. Food and Drug Administration (FDA) has approved Xgeva (denosumab), the first and only RANK Ligand inhibitor for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors. Xgeva was approved following a 6 month priority review by the FDA, a designation reserved for drugs that offer major advances in treatment or provide a treatment where no adequate therapy exists. Xgeva is not indicated for the prevention of SREs in patients with multiple myeloma.

"Today's approval of Xgeva illustrates what is possible when scientific innovation, commitment and investment come together to advance medicine," said Kevin Sharer, chairman and chief executive officer of Amgen. "A diagnosis of bone metastases is a major event for patients living with cancer, and the consequences can be devastating. We are pleased to offer this new advance to patients and their healthcare providers."

Bone metastases, the spread of cancer to the bones, are a serious concern for patients with advanced cancer and present a considerable burden to the healthcare system. Weakened bones due to metastases can lead to fractures and compression of the spinal cord and necessitate procedures like major surgery and radiation, designed to prevent or manage bone complications. The primary goal of treatment for bone metastases is to prevent the occurrence of debilitating and costly bone complications, which can disrupt a patient's life and cause disability, pain and hospitalization.

"As many as 3 out of 4 patients with advanced prostate, lung, and breast cancer will experience spread to their bones. Despite the availability of current treatments, a significant proportion of these patients still experience bone complications or are not candidates for existing treatment," said David H. Henry, M.D., clinical professor of medicine, and vice chair, Department of Medicine, Pennsylvania Hospital, University of Pennsylvania Healthcare System. "Based on the compelling science and robust clinical evidence seen with Xgeva, I expect this new option to quickly become a mainstay of cancer care and to play an important role in reducing the incidence of debilitating bone complications in patients with advanced cancer."

The RANK Ligand pathway, first discovered by Amgen scientists in the mid-1990s, is believed to play a central role in cancer-induced bone destruction, regardless of cancer type. 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 Clinical Trial Experience

The FDA approval of Xgeva is based on the results of three pivotal, Phase 3 head-to-head trials that evaluated Xgeva delivered every four weeks as a 120 mg subcutaneous injection versus Zometa (zoledronic acid) delivered every four weeks via a 15-minute intravenous infusion, adjusted for kidney function per the labeled instructions. The clinical program for Xgeva spanned more than 50 tumor types in over 5,700 patients. In the Phase 3 trials, Xgeva demonstrated a clinically meaningful improvement in preventing SREs compared to Zometa. Specifically, in patients with breast or prostate cancer and bone metastases, Xgeva was superior to Zometa in reducing the risk of SREs. In patients with bone metastasis due to other solid tumors or bone lesions due to multiple myeloma, Xgeva was noninferior (trending towards superiority) to Zometa in reducing the risk of SREs. Superiority was also seen in the integrated analysis of the Phase 3 studies.

Overall rates of adverse events and serious adverse events were generally similar between Xgeva and Zometa. Osteonecrosis of the jaw (ONJ) was infrequent, with no statistically significant difference between treatment arms. Hypocalcemia was more frequent in the Xgeva arm. Overall survival and progression-free survival were similar between arms in all three trials.

"As many as 70 percent of patients with prostate cancer that have metastasized to the bone are not currently receiving therapy to prevent complications from these bone metastases. This may be secondary to urologists lacking comfort or facilities to provide infusion treatment," said Neal D. Shore, M.D., FACS, medical director, Carolina Urologic Research Center. "Xgeva could provide increased treatment care options and accessibility for urologist's who treat advanced prostate cancer; as Xgeva is administered as a subcutaneous injection on a monthly basis. Also, Xgeva does not require dose adjustment for changes in renal function."

Economic Impact of SREs

The total economic burden of patients with bone metastases in the U.S. alone estimated to be $12.6 billion annually.(i) Patients who experience an SRE as a result of bone metastases incur significantly higher medical costs compared with those who do not experience such events. (ii, iii, iv) In addition, once patients experience an SRE, the risk of a subsequent SRE is increased. The costs of SREs vary by type and severity, ranging from relatively low costs for minor fractures to high cost events like spinal cord compression associated with hospitalization. Studies have shown that the costs of treating SREs are a significant cost burden.

Xgeva is an innovative therapy that significantly reduces debilitating and costly SREs. This can result in cost offsets due to the reduced incidence of SREs and related medical costs. Xgeva will cost $1,650 monthly based on wholesale acquisition cost.

Xgeva First Step Coupon Program

Amgen is committed to supporting patient access to important medicines through innovative programs including our newly established commercial co-pay program for Xgeva, financial support to independent third party co-pay foundations, and the Safety Net Foundation, which provides free products to uninsured patients who qualify. The Xgeva First Step Coupon Program is a landmark program among oncology commercial co-pay programs, as it is the first program under the medical benefit with no income eligibility requirement. The program is intended to provide assistance to eligible patients who need help meeting their deductible, co-insurance, and/or co-payment requirements under the medical benefit for Xgeva. Under this program, eligible patients will incur no out of pocket costs for their initial Xgeva injection and pay a maximum of $25 for subsequent injections.

Xgeva Regulatory Status

Amgen has also submitted marketing applications for Xgeva in the European Union, Australia, Canada and Switzerland. In Japan, Amgen is working with its licensing partner, Daiichi-Sankyo Company, Limited and a marketing application was submitted in August.

Xgeva Important Safety Information

Xgeva can cause severe hypocalcemia. Correct pre-existing hypocalcemia prior to Xgeva treatment. Monitor calcium levels and administer calcium, magnesium, and vitamin D as necessary. Advise patients to contact a healthcare professional for symptoms of hypocalcemia.

Osteonecrosis of the jaw 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.

The most common adverse reactions in patients receiving Xgeva were fatigue/asthenia, hypophosphatemia, and nausea. The most common serious adverse reaction in patients receiving Xgeva was dyspnea. The most common adverse reactions resulting in discontinuation of Xgeva were osteonecrosis and hypocalcemia. Please visit www.amgen.com for full prescribing information.

Denosumab is also marketed as Prolia in other indications.

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 75 percent of patients with metastatic disease.(v)

Approximately 50-70 percent of cancer patients with bone metastases will experience debilitating SREs.(vi, vii, viii) Events considered to be SREs include fractures, spinal cord compression, and severe bone pain that may require surgery or radiation.(ix) Such events can profoundly disrupt a patient's life and can cause disability and pain.(x, xi, xii)

Denosumab and Amgen's Research in Bone Biology

The denosumab development program demonstrates Amgen's commitment to researching and delivering pioneering medicines to patients with unmet medical needs. Amgen is studying denosumab in numerous tumor types across the spectrum of cancer-related bone diseases. Over 11,000 patients have been enrolled in the denosumab oncology clinical trials. In addition to this newly approved indication, Xgeva is also being investigated for its potential to delay bone metastases in prostate and breast cancer.

About Amgen

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, 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/.

Forward-Looking Statements

This news release contains forward-looking statements that are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission (SEC) reports filed by Amgen, including Amgen's most recent annual report on Form 10-K and most recent periodic reports on Form 10-Q and Form 8-K. Please refer to Amgen's most recent Forms 10-K, 10-Q and 8-K for additional information on the uncertainties and risk factors related to our business. Unless otherwise noted, Amgen is providing this information as of Nov.18, 2010 and expressly disclaims any duty to update information contained in this news release.

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CONTACT: Amgen, Thousand Oaks

Christine Regan: +1 (805) 447-5476 (media)

Lisa Rooney: +1 (805) 447-6437 (media)

Arvind Sood: +1 (805) 447-1060 (investors)

(i) Schulman KL, Kohles J. Economic burden of metastic bone disease in the U.S. American Cancer Society 2007:2334-2342.

(ii) Delea T, Langer C, McKiernan J, et al. The cost of treatment of skeletal-related events in patients with bone metastases from lung cancer. Oncology 2004;67:390-396.

(iii) Schulman KL, Kohles J. Economic burden of metastic bone disease in the U.S. American Cancer Society 2007:2334-2342.

(iv) GVD/2007:2334-2342.Barber ISPOR 2008 Poster

(v) Coleman RE. Skeletal complications of malignancy. Cancer. 1997; 80(suppl): 1588-1594.

(vi) 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.

(vii) 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.

(viii) Rosen LS, Gordon D, Tchekmedyian NS, et al. Nonsmall cell lung carcinoma and other solid tumors. Cancer. 2004;100:2613-2621.

(ix) 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.

(x) 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.

(xi) Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 2006;17:1726–1733.

(xii) 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.

(Logo: http://photos.prnewswire.com/prnh/20081015/AMGENLOGO )

SOURCE Amgen

CONTACT: Amgen, Thousand Oaks, Christine Regan: +1-805-447-5476 (media), Lisa Rooney: +1-805-447-6437 (media), Arvind Sood: +1-805-447-1060 (investors)


Web Site: http://www.amgen.com

Posted: November 2010

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Xgeva (denosumab) FDA Approval History

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