Studies Published in The New England Journal of Medicine Highlight Potential New Option in the Treatment of Bone Loss



    
       Twice-Yearly Administration of Denosumab Resulted in 68 Per cent
     Reduction in Risk for a Vertebral Fracture and 40 Per cent Reduction
           in Risk for a Hip Fracture in Women with Postmenopausal
                                 Osteoporosis

         Denosumab Administered Twice-Yearly Reduced the Incidence of
      New Vertebral Fractures by 62 Per cent in Men with Non-Metastatic
           Prostate Cancer Undergoing Androgen Deprivation Therapy
    

    MISSISSAUGA, ON, Aug. 11 /CNW/ - Amgen today announced the publication of
results from two pivotal Phase 3 studies investigating the safety and
effectiveness of denosumab at reducing fracture risk in more than 7,800 women
with postmenopausal osteoporosis and in more than 1,400 men with
non-metastatic prostate cancer undergoing androgen deprivation therapy (ADT).
In both studies, published today in The New England Journal of Medicine
(NEJM),(1,2) patients receiving twice-yearly denosumab experienced
statistically significant increases in bone mineral density (BMD) compared to
placebo, associated with more than 60 per cent reduction in vertebral fracture
in both patient populations. These data were previously reported by Amgen at
medical congresses.
    "The discovery of the RANK Ligand pathway represents a significant
advance in the understanding of bone biology," said Roland Baron, PhD, DDS,
professor and chair of department of Oral Medicine, Infection, and Immunity at
the Harvard School of Dental Medicine. "These results demonstrate that
targeting the RANK Ligand pathway with denosumab could represent a promising
new approach in two different disease settings characterized by bone loss."

    
    FREEDOM Osteoporosis Study Results: Statistically Significant Fracture
    Reduction Seen Across the Skeleton in Postmenopausal Women with
    Osteoporosis
    

    Results from the FREEDOM (Fracture REduction Evaluation of Denosumab in
Osteoporosis every six Months) study showed that women receiving a
subcutaneous injection of denosumab twice-yearly experienced a 68 per cent
reduction in the risk of suffering a vertebral (spine) fracture compared to
those receiving placebo as well as a 40 per cent reduction in the risk of
suffering a hip fracture and a 20 per cent reduction in the risk of suffering
a nonvertebral (non-spine) fracture. Over the three years of this
multi-centre, randomized, double-blind placebo-controled study, women treated
with denosumab experienced statistically significant increases in BMD (8.8 per
cent at the lumbar spine and 6.4 per cent at the total hip). Nine Canadian
sites participated in the study involving 110 patients from Canada.
    "These data indicate that denosumab may represent a potential new
approach in the management of postmenopausal osteoporosis," said Dr. Jonathan
Adachi, rheumatologist with Hamilton's McMaster University and FREEDOM
investigator. "Not only is denosumab showing statistically significant
efficacy at all key sites in the skeleton, but since it may be given as a
twice-yearly injection, the medication may help with patient compliance to
this treatment."
    Fracture is one of the most common health events suffered by
postmenopausal women with osteoporosis.(3) As many as two million Canadians
may be at risk of osteoporotic fractures during their lifetime(4). A woman who
has broken a bone as a result of osteoporosis has more than an
eight-out-of-ten chance of breaking another bone.(5) Half of women who break a
hip, a life changing event, will permanently need assistance to walk.(6)
    "Despite the high risk of breaking bones and all of the potential long
term consequences such as loss of independence and greater risk of premature
death, many people face challenges with their treatment," says Julie Foley,
President and CEO, Osteoporosis Canada. "Compliance with medication schedules
can be problematic for many reasons, and we welcome new treatments that expand
the range of options for physicians and their patients."
    The overall incidence and type of side effects with denosumab were
similar to placebo in the FREEDOM study. Rates of adverse events (AEs) were
similar in both groups (93 per cent). Rates of serious AEs were 25.8 per cent
for denosumab and 25.1 per cent for placebo. The most common AEs across both
treatment arms were arthralgia, back pain, hypertension and nasopharyngitis.
There were no reported cases of osteonecrosis of the jaw among patients taking
denosumab. Serious adverse events of skin infections, predominantly
cellulitis, were reported more commonly in the denosumab group (0.4% vs. less
than 0.1%).

    
    HALT Study Results: First Published Study to Demonstrate Fracture
    Prevention in Men with Non-Metastatic Prostate Cancer Undergoing ADT
    

    Results from the HALT study in 1,468 men undergoing ADT for
non-metastatic prostate cancer show that patients treated with denosumab
experienced a 62 per cent reduction in the risk of suffering a new vertebral
facture with denosumab compared to placebo at 36 months, with significant
reduction observed as early as month-12. Thirty-five Canadian sites
participated in the study and of the 1,468 patients involved in the study, 398
were in Canada.
    Bone loss and increased fracture risk are serious and under-recognized
consequences of ADT.(7,8) Currently, there are no approved therapies
specifically for patients experiencing bone loss due to hormone ablation
therapy.
    In this multi-center, randomized, double-blind, placebo-controlled study,
men receiving 60 mg denosumab administered subcutaneously twice-yearly
experienced a 6.7 per cent increase in BMD at the lumbar spine compared to
those receiving placebo at 24 months (primary endpoint). Increases in BMD at
the lumbar spine were observed as early as one month after starting treatment
with denosumab and continued to increase throughout the study. In addition,
denosumab produced statistically significant increases in BMD at non-vertebral
sites (total hip 4.8 per cent, femoral neck 3.9 per cent, and distal 1/3
radius 5.5 per cent), compared to placebo.
    "Bone loss and fractures in men with advanced prostate cancer can be
debilitating side effects of androgen deprivation therapy and much of the
damage can happen in the early stages of treatment," said Dr. Fred Saad,
Professor and Chair of Urology, University of Montreal and a clinical
investigator for the HALT study. "Study results show that denosumab can
increase bone mineral density as early as one month after starting therapy and
continuing for the duration of the 3-year study."
    "Bone loss is a serious concern for men with prostate cancer," says Bob
Shiell, Managing Director of the Prostate Cancer Canada Network.
    In the HALT trial, the overall incidence and type of side effects with
denosumab were similar to placebo. Rates of adverse events were similar in
both groups (87 per cent). Rates of serious AEs were 35 per cent for denosumab
and 31 per cent for placebo. The most common adverse events across both
treatment arms were arthralgia (joint pain), back pain, constipation, pain in
extremity, and hypertension. There were no reported cases of osteonecrosis of
the jaw among patients taking denosumab. New primary malignancies were
reported in 5% of patients in each group. Serious AEs of infections were
reported in 6 per cent of denosumab-treated patients and in 5 per cent of
placebo-treated patients.
    "The discovery of the RANK Ligand pathway by Amgen scientists has
significantly advanced our understanding of bone biology," said Dr. Daniel
Billen, Vice President and General Manager, Amgen Canada Inc. "The research we
are conducting into denosumab illustrates our commitment to helping patients
by using innovative therapies that target the root cause of disease."

    About Denosumab

    Denosumab is the first fully human monoclonal antibody in late stage
clinical development that specifically targets RANK Ligand, an essential
regulator of osteoclasts (the cells that break down bone). Denosumab is being
investigated for its potential to inhibit all stages of osteoclast activity
through a targeted mechanism. Denosumab is being studied in a range of bone
loss conditions including postmenopausal osteoporosis (PMO) and bone loss in
patients undergoing hormone ablation for prostate and breast cancer.
    The safety and efficacy of denosumab is still under investigation. Amgen
has submitted marketing applications for denosumab, which are currently under
review by health authorities in Canada, the United States, European Union,
Switzerland and Australia. Health Canada has not yet granted market
authorization for denosumab for any treatment or indication.

    Osteoporosis: Impact and Prevalence

    Often referred to as the "silent epidemic," osteoporosis is a global
problem that is increasing in significance as the population of the world both
increases and ages. In Canada, one in four women over 50 suffer from
osteoporosis(8) and yet fewer than 20 per cent of women who have had an
osteoporotic fracture are treated for the disease.(9) The World Health
Organization (WHO) has recently identified osteoporosis as a priority health
issue along with other major non-communicable diseases.
    In Canada, the annual direct costs of treating osteoporotic fractures of
people in the workplace are estimated to be approximately $1.9 billion.(10) It
has been reported that osteoporosis results in more hospital bed-days than
stroke, myocardial infarction or breast cancer.(11)

    Bone Loss Due to Hormone Ablation Therapy

    In Canada, prostate cancer and breast cancer are two of the most frequent
types of cancer affecting men and women, respectively. It is common for
prostate cancer and breast cancer patients to receive hormone ablation
therapies that can lead to a decrease in bone mass and increased risk of
fractures.
    Currently there are no approved therapies for bone loss in patients
undergoing hormone ablation for either prostate or breast cancer.

    About Amgen Canada

    Amgen Canada Inc. is the Canadian affiliate of Amgen Inc. 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
www.amgen.ca.

    Forward-Looking Statements

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    References

    1.  Cummings SR, et al. Twice Yearly Denosumab, a Monoclonal Antibody to
        RANK-ligand, for Prevention of Fractures in Postmenopausal Women with
        Osteoporosis. N Engl J Med, 2009 Aug. 20; published online at
        www.njem.org on Aug. 11, 2009.
    2.  Smith MR, et al. Denosumab for the Prevention of Bone Loss and
        Fractures in Men Receiving Androgen Deprivation Therapy in Non-
        Metastatic Prostate Cancer. N Engl J Med, 2009 Aug. 20; published
        online at www.njem.org on Aug. 11, 2009.
    3.  Melton LJ, et al. (1992) Perspective. How Many Women Have
        Osteoporosis? J Bone Miner Res, 1992;7:1005.
    4.  Hanley DA, Josse RG. Prevention and management of osteoporosis:
        consensus statements from the Scientific Advisory Board of the
        Osteoporosis Society of Canada: 1. Introduction. CMAJ 1996;155:921-3.
    5.  Kanis JA, et al. A Meta-Analysis of Previous Fracture and Subsequent
        Fracture Risk. Bone, 2004;35:375.
    6.  Magaziner J, et al. Predictors of Functional Recovery One Year
        Following Hospital Discharge for Hip Fracture: A Prospective Study. J
        Gerontol, 1990;45:M101.
    7.  Higano 2008; Higano 2004; Conde 2003; Smith 2001; Pfeilschifter 2000.
    8.  Oefelein MG, Ricchiuti V, Conrad W, Resnick MI. Skeletal fractures
        negatively correlate with overall survival in men with prostate
        cancer. J Urol. 2002;168:1005-1007.
    9.  Hajcsar EE, Hawker G, Bogoch ER. et al. Investigation and treatment
        of osteoporosis in patients with fragility fractures. CMAJ. 2000
        Oct 3;163(7):819-22.
    10. "Invest in Your Bones: Osteoporosis in the Workplace." International
        Osteoporosis Foundation. 2002.
    11. Lippuner K, et al. "Incidence and direct medical costs of
        hospitalisations due to osteoporotic fractures in Switzerland."
        Osteoporosis International.1997;7:414-25.
    




For further information:

For further information: Sabrina Paiva, Amgen Canada Inc., Tel: (905)
285-3145, Email: spaiva@amgen.com

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