Treatment with XGEVA® (Denosumab) now one step closer for men with advanced prostate cancer with bone metastases

CDR recommends provinces fund latest treatment for reducing the risk of debilitating bone complications

MISSISSAUGA, ON, Nov. 21, 2011 /CNW/ - The Canadian Drug Expert Committee (CDEC), through the Common Drug Review (CDR), recommended to all participating provincial drug plans that XGEVA^® (denosumab), an approved treatment for reducing the risk of skeletal-related events, or SREs, such as pathological fracture, radiation to bone, spinal cord compression or surgery to bone, be listed for the prevention of SREs in patients with castrate-resistant prostate cancer that has metastasized to bone in jurisdictions that list zoledronic acid for the same indication. With this recommendation, Canadians suffering from advanced prostate cancer are one step closer to having access to XGEVA, a RANK-Ligand inhibitor.

"Amgen Canada is very pleased that the CDR has recognized the value of XGEVA for prostate cancer patients," said Anand Varadan, Vice-President and General Manager, Amgen Canada Inc. "This decision clears the pathway for provincial drug plans to add XGEVA to their drug formulary."

Amgen Canada continues to work with each province to ensure that men with advanced prostate cancer and bone metastases who rely on provincial drug plans will have access to XGEVA.

"The most common area for advanced prostate cancer to spread is to the bone," said Dr. Anthony Finelli, surgical oncologist, Princess Margaret Cancer Program, University Health Network and Associate Professor, University of Toronto. "As the consequences of bone metastases can have a significant impact on men living with cancer, I am pleased that men with this type of prostate cancer are one step closer to accessing this new treatment option."

Bone metastases, the spread of cancer from its site of origin to the bones, are a serious concern for patients with advanced cancer. Up to 90 per cent of men with advanced prostate cancer develop bone metastases throughout the course of their disease.^1,2,3 Many of these patients do not receive bone-targeted therapy. Bones weakened by metastases can lead to fractures and compression of the spinal cord and necessitate procedures like major surgery and radiation. The primary goal for using bone-targeted therapies is to reduce the risk of these debilitating and costly bone complications, which can disrupt a patient's life and cause disability, pain and hospitalization.

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.^4,5 In addition, once patients experience an SRE, the risk of a subsequent SRE is increased.⁶  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. The total economic burden of patients with bone metastases in the U.S. alone is estimated to be $12.6 billion annually.⁷

Unlike currently approved bone-targeted therapies which must be administered via intravenous infusion, XGEVA is delivered as an injection under the skin every four weeks. XGEVA is not cleared by the kidneys, therefore dose adjustment for renal impairment is not required,⁸ as needed with intravenously administered bisphosphonates.

Important Safety Information
XGEVA is not indicated for reducing the risk of developing SREs in patients with multiple myeloma.⁹

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.¹⁰

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.¹¹

The most common adverse events in patients receiving XGEVA versus zoledronic acid were fatigue (27.1 per cent vs 27.0 per cent respectively) and asthenia (21.4 per cent vs 21.9 per cent respectively); hypophosphatemia (32.1 per cent vs 19.6 per cent respectively); and nausea (30.8 per cent vs 31.6 per cent respectively). The most common adverse reactions resulting in discontinuation of XGEVA were osteonecrosis of the jaw and hypocalcemia.¹²  Please visit www.amgen.ca for full product monograph.

Denosumab is also marketed as Prolia^® for other indications.

About XGEVA^® (denosumab)
XGEVA (denosumab), a RANK-Ligand inhibitor, is approved by Health Canada for reducing the risk of developing skeletal-related events (SREs) in adults with bone metastases from solid tumours.¹³ XGEVA is not indicated for reducing the risk of developing skeletal-related events in patients with multiple myeloma.¹⁴

Prolia^® is the trade name for denosumab in postmenopausal osteoporosis for which it is administered once every six months subcutaneously as a 60 mg single dose pre-filled syringe.

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 up to 90 per cent of patients with metastatic disease.^15,16,17

Approximately 50-70 per cent of cancer patients with bone metastases will experience debilitating SREs.^18,19,20 Events considered to be SREs, which may require surgery or radiation, include fractures, spinal cord compression and severe bone pain.²¹ Such events can profoundly disrupt a patient's life and can cause disability and pain.^{22, 23, 24}

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, 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 www.amgen.ca. Follow us on www.twitter.com/amgen.

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 U.S. 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 November 21, 2011 and expressly disclaims any duty to update information contained in this news release.

No forward-looking statement can be guaranteed and actual results may differ materially from those we project.  Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product.  Further, preclinical results do not guarantee safe and effective performance of product candidates in humans.  The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models.  The length of time that it takes for us to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future.  We develop product candidates internally and through licensing collaborations, partnerships and joint ventures.  Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship.  Also, we or others could identify safety, side effects or manufacturing problems with our products after they are on the market.  Our business may be impacted by government investigations, litigation and products liability claims. We depend on third parties for a significant portion of our manufacturing capacity for the supply of certain of our current and future products and limits on supply may constrain sales of certain of our current products and product candidate development.

In addition, sales of our products are affected by the reimbursement policies imposed by third-party payors, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and health care cost containment as well as applicable legislation affecting pharmaceutical pricing and reimbursement.  Government and others' regulations and reimbursement policies may affect the development, usage and pricing of our products.  In addition, we compete with other companies with respect to some of our marketed products as well as for the discovery and development of new products.  We believe that some of our newer products, product candidates or new indications for existing products, may face competition when and as they are approved and marketed.  Our products may compete against products that have lower prices, established reimbursement, superior performance, are easier to administer, or that are otherwise competitive with our products. In addition, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors and there can be no guarantee of our ability to obtain or maintain patent protection for our products or product candidates.  We cannot guarantee that we will be able to produce commercially successful products or maintain the commercial success of our existing products.  Our stock price may be affected by actual or perceived market opportunity, competitive position, and success or failure of our products or product candidates.  Further, the discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations.

XGEVA^® is a registered trademark of Amgen Inc., used with permission.

References
___________________________
¹ Tannock IF, de Wit, R, Berry WR, et al. Docetaxel plus Prednisone or Mitoxantrone plus Prednisone for Advanced Prostate Cancer. N Engl J Med 2004;351:1502-12

² Scher HI, Morris MJ, Kelly MK. Prostate Cancer Clinical Trial End points: "RECIST"ing a Step Backwards. Clin Cancer Res 2005:11:5223-5232. Published online July 20, 2005.

³ Petrylak DP, Tangen CM, Hussain MHA, et al. Docetaxel and Estramustine Compared with Mitoxantrone and Prednisone for Advanced Refractory Prostate Cancer. N Engl J Med 2004;351:1513-20.

⁴ 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.

⁵ Schulman KL, Kohles J. Economic burden of metastic bone disease in the U.S. American Cancer Society 2007:2334-2342.

⁶ Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, et al. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Instit 2004;96(11):879-882.

⁷ Schulman KL, Kohles J. Economic burden of metastatic bone disease in the U.S. American Cancer Society 2007:2334-2342.

⁸ XGEVA^TM Product Monograph. Amgen Canada Inc. October 14, 2011

⁹  XGEVA^TM Product Monograph. Amgen Canada Inc. October 14, 2011

¹⁰   XGEVA^TM Product Monograph. Amgen Canada Inc. October 14, 2011

¹¹  XGEVA^TM Product Monograph. Amgen Canada Inc. October 14, 2011

¹²  XGEVA^TM Product Monograph. Amgen Canada Inc. October 14, 2011

¹³   XGEVA^TM Product Monograph. Amgen Canada Inc. October 14, 2011

¹⁴   XGEVA^TM Product Monograph. Amgen Canada Inc. October 14, 2011

¹⁵ Tannock IF, de Wit, R, Berry WR, et al. Docetaxel plus Prednisone or Mitoxantrone plus Prednisone for Advanced Prostate Cancer. N Engl J Med 2004;351:1502-12

¹⁶ Scher HI, Morris MJ, Kelly MK. Prostate Cancer Clinical Trial End points: "RECIST"ing a Step Backwards. Clin Cancer Res 2005:11:5223-5232. Published online July 20, 2005.

¹⁷ Petrylak DP, Tangen CM, Hussain MHA, et al. Docetaxel and Estramustine Compared with Mitoxantrone and Prednisone for Advanced Refractory Prostate Cancer. N Engl J Med 2004;351:1513-20.

¹⁸ 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.

¹⁹   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.

²⁰  Rosen LS, Gordon D, Tchekmedyian NS, et al. Nonsmall cell lung carcinoma and other solid tumors. Cancer. 2004;100:2613-2621.

²¹ 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.

²² Nørgaard M, Jensen AØ, Jacobsen JB, Cetin K, Fryzek JP, Sørensen HT.  Skeletal related events, bone metastatis and survival of prostate cancer: a population based cohort study in Denmark (1999 to 2007).J Urol 2010; 184:162-167.

²³ Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 2006;17:1726-1733.

²⁴   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.

 

For further information:

Sabrina Paiva
Amgen Canada
905-285-3145
[e-mail]

Fiona Robinson
Hill & Knowlton Canada
416-413-4737
[e-mail]