FDA Approves Amgen's Prolia(TM) (Denosumab) for Treatment of Postmenopausal Women With Osteoporosis at High Risk for Fracture

06.01.2010 |
Given As An Injection Every Six Months, Prolia Reduced Risk Of Fracture At The Spine, Hip And Other Sites

THOUSAND OAKS, Calif., June 1, 2010 /PRNewswire via COMTEX/ --Amgen Inc. (Nasdaq: AMGN) today announced that the U.S. Food and Drug Administration (FDA) has approved Prolia(TM) (denosumab) for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy. Prolia, the first and only FDA-approved RANK Ligand inhibitor, is an every six month 60 mg subcutaneous injection administered by a health care professional.

"Today's FDA approval of Prolia is the culmination of a scientific journey that started more than 15 years ago with Amgen's discovery of an essential pathway that regulates bone metabolism," said Kevin Sharer, chairman of the board and chief executive officer of Amgen. "Prolia is the result of this discovery and offers an important new medicine for postmenopausal women with osteoporosis at high risk for fracture. Amgen is proud to make this new treatment option available to physicians and patients."

Prolia's approval is based on a pivotal three-year Phase 3 study involving 7,808 postmenopausal women with osteoporosis. Treatment with Prolia resulted in greater bone density, stronger bones, and reduced risk for vertebral, hip and non-vertebral fractures measured at three years.(i)

"For the many osteoporosis patients who are at high risk for fracture, Prolia's approval marks the first new class of medicine introduced in nearly a decade," said Felicia Cosman, M.D., clinical director of the National Osteoporosis Foundation and medical director of the Clinical Research Center at Helen Hayes Hospital in New York. "Prolia is a new treatment that reduces the risk of fracture at key sites, including the hip and spine, and is given as a convenient twice-yearly shot just under the skin. It will be a welcome new option."

"While this is an important milestone for Amgen, it is even more important for the postmenopausal patients with osteoporosis who are at high risk for fracture," said Robert A. Bradway, president and chief operating officer of Amgen. "We have priced Prolia responsibly while reflecting its strong therapeutic value and expect to make it commercially available in the U.S. within the next week."

Prolia Clinical Data

The pivotal three-year Phase 3 Fracture REduction Evaluation of Denosumab in Osteoporosis every six Months (FREEDOM) study in 7,808 women with postmenopausal osteoporosis demonstrated that Prolia, administered as a 60mg subcutaneous injection every six months, compared with placebo at three years resulted in: (ii)

  • A 68 percent reduction in vertebral fractures (4.8 percent absolute risk reduction). The incidence of new spine fractures was 2.3 percent with Prolia vs. 7.2 percent with placebo;
  • A 40 percent reduction in hip fractures (0.3 percent absolute risk reduction). The incidence of hip fractures was 0.7 percent with Prolia vs. 1.2 percent with placebo;
  • A 20 percent reduction in non-vertebral fractures (1.5 percent absolute risk reduction). The incidence of non-spine fractures was 6.5 percent with Prolia vs. 8 percent with placebo;
  • Significant bone density increases at all key sites measured (8.8 percent at the lumbar spine, 6.4 percent at the total hip, and 5.2 percent at the femoral neck).

Prolia is contraindicated in patients with hypocalcemia. Pre-existing hypocalcemia must be corrected prior to initiating Prolia. Hypocalcemia may worsen, especially in patients with severe renal impairment. All patients should be adequately supplemented with calcium and vitamin D.

In the pivotal study, serious infections leading to hospitalizations were reported more frequently in the Prolia-treated patient group. Serious skin infections, as well as infections of the abdomen, urinary tract and ear, were more frequent in patients treated with Prolia. Patients should be advised to seek prompt medical attention if they develop signs or symptoms of severe infection, including cellulitis. Endocarditis was reported more frequently in the Prolia-treated patient group. Epidermal and dermal adverse events such as dermatitis, rashes, and eczema have been reported. Discontinuation of Prolia should be considered if severe symptoms develop.

Prolia resulted in significant suppression of bone remodeling. The significance of these findings is unknown. The long-term consequences of the degree of suppression of bone remodeling observed with Prolia may contribute to adverse outcomes such as osteonecrosis of the jaw (ONJ), atypical fractures, and delayed fracture healing. ONJ has been reported in patients with Prolia. Patients should be monitored for these adverse outcomes. The most common adverse reactions (> 5 percent and more common than placebo) were back pain, pain in extremity, musculoskeletal pain, hypercholesterolemia, and cystitis. Pancreatitis has also been reported with Prolia.

Commitment to Safety

Amgen has worked with the FDA to create several programs to help physicians and patients make treatment decisions for postmenopausal women with osteoporosis at high risk for fracture based on the most comprehensive and current Prolia benefit:risk information and to facilitate post-marketing safety surveillance. These include:

  • A Risk Evaluation and Mitigation Strategy (REMS) to communicate the risks of Prolia, which consists of a communication plan for health care providers and a medication guide for patients.
  • Comprehensive post-marketing surveillance. Amgen continues to gather data from extension studies in more than 4,500 women with postmenopausal osteoporosis who will have exposure to Prolia for up to 10 years. In addition, Amgen will implement an international Prolia long-term safety observational study to assess pre-specified adverse events of special interest based on seven existing data systems from five countries, which will include healthcare administrative databases, electronic medical records, and national health registries. These women with postmenopausal osteoporosis who received Prolia will be followed long term. Finally, Amgen is launching the Prolia Post marketing Active Safety Surveillance Program to monitor the long-term safety of Prolia and improve the quality of data collected in the post-marketing setting. This program is intended to enhance the adverse event reporting system by soliciting reports of pre-specified adverse events of special interest.

Why New Options are Needed to Treat Postmenopausal Osteoporosis

In the U.S., one in two women over the age of 50 with postmenopausal osteoporosis will experience a fracture in her remaining lifetime.(iii) These fractures can have severe clinical consequences. (iv)(v) In 2005, osteoporosis-related fractures were responsible for an estimated $19 billion in costs and by 2025 experts predict that these costs will rise to approximately $25 billion.(vi)(vii)

Postmenopausal women with osteoporosis who have experienced a fracture are at increased risk for another fracture.(viii)(ix)(x) An analysis of data combined over multiple U.S. health plans showed that approximately 50 percent of patients discontinue oral bisphosphonate therapy within the first year.(xi) Some patients cannot tolerate available osteoporosis therapy. Among patients who discontinue these treatments, many do so because of side effects including intolerance. (xii)(xiii)(xiv) Poor adherence can increase fracture risk and has been associated with more fracture-related hospitalizations. (xv)

There remain opportunities for new therapeutic options for women with postmenopausal osteoporosis at high risk for fracture, which include those with prior osteoporotic fracture, or those with two or more risk factors, or patients with osteoporosis who are intolerant to available therapy, or patients with osteoporosis who have failed available therapy. Prolia may be considered for these patients.

Introducing ProliaPlus(TM)

ProliaPlus is a multi-faceted product support program designed to provide comprehensive assistance to healthcare providers, patients, and their caregivers to help facilitate access to Prolia for appropriate patients.

ProliaPlus provides information and assistance on issues related to product insurance coverage to physician offices. Additionally, upon request, ProliaPlus will remind patients and providers about when the patient's next dose is due, thus helping to support patient adherence to therapy. ProliaPlus will also have information on the availability of potential financial assistance programs.

Providing Value at a Competitive Price

Prolia will cost $825 per 60 mg injection (based on "wholesale acquisition cost" or WAC). Prolia's price is competitive with other branded osteoporosis therapies while reflecting its positive clinical profile for patients at high risk for fracture.

Reimbursement Pathways for Prolia

Payers will determine, based on the prescribing information including the instruction that Prolia should be administered by a Health Care Professional, whether Prolia is covered under their medical and/or pharmacy benefit. Amgen is prepared to support both medical and pharmacy benefit paths based on the payer's reimbursement decisions. Product will be stocked at wholesalers within a week of approval and Amgen is fully prepared for rapid replenishment to the wholesale level as required. In addition, single unit syringe ordering will be available to health care providers from their distributor. Because Prolia has been approved in June, most patients who receive Prolia will only receive one dose this year.

To view the Prolia Prescribing Information and REMS materials, click here: wwwext.amgen.com.

About Prolia(TM) (denosumab)

Prolia is the first and only approved therapy that specifically targets RANK Ligand, an essential regulator of osteoclasts (the cells that break down bone).

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/.

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    (i)  Cummings SR et al. Denosumab for Prevention of Fractures in
     Postmenopausal Women with Osteoporosis. N Engl J Med. 2009;
    (ii)  Prolia Prescribing Information.
    (iii)  Osteoporosis Fast Facts. Washington (DC): National
     Osteoporosis Foundation. Accessed on May 10, 2010 at http://
    (iv)  National Osteoporosis Foundation. http://www.nof.org/
     professionals/pdfs/NOF_ClinicianGuide2009_v7.pdf, Accessed May 13,
    (v)  Cooper C. The crippling consequences of fractures and their
     impact on quality of life. Am J Med. 1997 Aug 18;103(2A):12S-17S;
     discussion 17S-19S.
    (vi)  Burge R et al. Incidence and economic burden of osteoporosis-
     related fractures in the United States, 2005-2025. J Bone Miner
     Res. 2007 Mar;22(3):465-75.
    (vii)  Osteoporosis Fast Facts. Washington (DC): National
     Osteoporosis Foundation. Accessed on April 29, 2010 at http://
    (viii)  Kanis JA et al. A Meta-Analysis of Previous Fracture and
     Subsequent Fracture Risk. Bone. 2004;35(2):375-82.
    (ix)  Lindsay R et al. Risk of new vertebral fracture in the year
     following a fracture. JAMA. 2001 Jan 17;285(3):320-33.
    (x)  Klotzbuecher CM et al. Patients with prior fractures have an
     increased risk of future fractures: a summary of the literature and
     statistical synthesis. J Bone Miner Res. 2000 Apr;15(4):721-39.
    (xi)  Weycker D. et al. Compliance with drug therapy for
     postmenopausal osteoporosis. Osteoporos Int. 2006;17(11):1645-52.
     Epub 2006 Jul 22.
    (xii)  Ettinger B et al, Clinic visits and hospital admissions for
     care of acid related upper gastrointestinal disorders in women using
     alendronate for osteoporosis. Amer J Man Care,1998 Oct;
    (xiii)  Tosteson A et al. Early discontinuation of treatment for
     osteoporosis. Am J Med 2003 Aug 15;115:209-16.
    (xiv)  Lewiecki EM et al. Adherence to and gastrointestinal
     tolerability of monthly oral or quarterly intravenous ibandronate
     therapy in women with previous intolerance to oral bisphosphonates:
     a 12-month, open-label, prospective evaluation. Clin Ther. 2008
    (xv)  Siris ES et al. Adherence to bisphosphonate therapy and
     fracture rates in osteoporotic women: relationship to vertebral and
     nonvertebral fractures from 2 US claims databases. Mayo Clin Proc.
     2006 Aug;81(8):1013-22.

    CONTACT: Amgen, Thousand Oaks
    Sarah Reines: (805) 447-9783 (media)
    Kerry Beth Daly: (805) 447-3020 (media)
    Arvind Sood: (805) 447-1060 (investors)

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SOURCE Amgen Inc.