Ontario men gain access to innovative treatment, Xgeva®

Targeted therapy to reduce the risk of bone complications now available to prostate cancer patients

Please Note:  This information is intended for Canadian media only.

MISSISSAUGA, ON, April 24, 2012 /CNW/ - Amgen Canada today announced that the Ontario government is providing access to XGEVA^® (denosumab), a unique treatment for reducing the risk of bone complications, or skeletal-related events (SREs), such as fracture, radiation to bone, spinal cord compression or surgery to bone, in men with prostate cancer.

"Amgen Canada is pleased that the Ontario Public Drug Programs will be making this new treatment available to help men avoid potentially debilitating and costly bone complications arising from prostate cancer," said Dr. Clive Ward-Able, Executive Director, Research and Development, Amgen Canada Inc.

In November 2011, the Canadian Drug Expert Committee (CDEC), through the Common Drug Review (CDR), recommended to all participating provincial drug plans that XGEVA be listed for the prevention of SREs in patients with castration-resistant prostate cancer that has metastasized to bone in jurisdictions that list zoledronic acid (Zometa) for the same indication.

Based on the results of three pivotal, Phase 3 head-to-head trials, XGEVA demonstrated a clinically meaningful improvement by demonstrating superiority in reducing the risk of developing SREs compared to Zometa in patients with breast or prostate cancer and bone metastases. In addition, unlike most bone-targeted therapies on the market today which must be administered via intravenous infusion, XGEVA is delivered as an injection under the skin, 120 mg once every four weeks. XGEVA is not cleared by the kidneys; therefore, dose adjustment for renal impairment is not required.

The Ontario Public Drug Programs will reimburse XGEVA under the Exceptional Access Program and through Cancer Care Ontario's New Drug Funding Program for patients with prostate cancer who meet the following criteria:

Treatment of bony metastases for patients with hormone refractory prostate cancer as determined by an elevated PSA level, or evidence of progressive bony disease¹, despite castrate serum testosterone levels (<1.7nmol/L or <50ng/dL).

¹Progressive bony disease should be demonstrated by progressive changes in radionucleotide bone scan or clinical signs of disease progression (e.g., pathological fracture or increasing bone pain).

Note: Patients who have undergone orchiectomy do not need to provide a serum testosterone level.

Dose: 120 mg SC every four weeks

"More than 70 per cent of all advanced prostate cancer patients whose cancer has spread to the bone remain untreated, putting them at risk of debilitating bone complications," said Dr. Anthony Finelli, surgical oncologist, Princess Margaret Cancer Program, University Health Network and Associate Professor, University of Toronto. "Men in Ontario with advanced prostate cancer will now have access to a new, targeted treatment which can play an important role in reducing the incidence and impact of these complications."

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

Important Safety Information
XGEVA is not indicated for reducing the risk of developing SREs in patients with multiple myeloma.⁸

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.⁸

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.⁸

The most common adverse events observed in clinical trials of 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.⁸ Please visit www.amgen.ca for the full product monograph.

Denosumab is also marketed as Prolia^® for other indications. Patients being treated with XGEVA should not receive Prolia.

About XGEVA^® (denosumab)
XGEVA (denosumab) is indicated for reducing the risk of developing skeletal-related events in patients with bone metastases from breast cancer, prostate cancer, non-small cell lung cancer, and other solid tumours.⁸ XGEVA is not indicated for reducing the risk of developing skeletal-related events in patients with multiple myeloma.⁸

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.

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 April 24, 2012 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

Sabrina Paiva
Amgen Canada
905-285-3145
[email protected]

Fiona Robinson
Hill + Knowlton Strategies
416-413-4737
[email protected]