THOUSAND OAKS, Calif.,
Oct. 12, 2015 /PRNewswire/ -- Amgen
(NASDAQ:AMGN) today announced results from a seven-year,
single-arm, open-label extension of the three-year randomized,
double-blind, placebo-controlled, multicenter, international Phase
3 Fracture Reduction Evaluation of Denosumab in Osteoporosis every
six Months (FREEDOM) study. In this final analysis, treatment with
Prolia® (denosumab) for up to 10 years showed that the
overall incidence of adverse events (AEs) and serious AEs remained
consistent over the duration of the study with a low fracture
incidence. In addition, postmenopausal women with osteoporosis on
Prolia continued to show gains in bone mineral density (BMD) over
10 years. The findings were presented during a late-breaking oral
presentation session at the American Society for Bone and Mineral
Research (ASBMR) 2015 Annual Meeting in Seattle today.
"Osteoporosis generally requires long-term therapy, and it is
important to maintain a favorable balance of benefit versus risk
over that course of treatment," said lead investigator Henry G. Bone III, M.D., director of the
Michigan Bone and Mineral Clinic, Detroit. "Long-term therapy with denosumab for
up to 10 years produced progressively increased bone density
measurements. The safety profile remained consistent over the
duration of the study, including a low fracture incidence. These
long-term results are important for patients and those who care for
them."
The findings are from an extension of the pivotal Phase 3
FREEDOM fracture study (NCT00089791), which enrolled 7,808 women
with postmenopausal osteoporosis. In the fracture study,
participants were randomly assigned to receive Prolia (60 mg) or
placebo subcutaneously every six months for three years, after
which they could choose to enter a seven-year extension study.
Eligibility criteria for the extension study included completion of
the pivotal Phase 3 fracture trial, not missing more than one dose
of investigational product (either Prolia or placebo) in the
pivotal Phase 3 fracture trial, and not receiving any other
osteoporosis medications. In the extension, all subjects,
regardless of original randomization, received open-label Prolia
(60 mg) every six months. The long-term group received up to 10
years of Prolia (three years in the pivotal Phase 3 fracture study
and seven years in the extension) and the cross-over group
received up to 7 years of Prolia (three years placebo in the
pivotal Phase 3 fracture study, seven years Prolia in the
extension). Of the 4,550 participants who enrolled in the
extension, 2,626 completed the extension study.
David Kendler, M.D., FRCP(C),
director, Prohealth Clinical Research in Vancouver, British
Columbia and study investigator, noted, "Osteoporosis is a chronic
condition, and many patients will be on lifelong therapy to help
reduce the risk of fragility fractures. As a physician treating
many patients with osteoporosis, long-term safety data is very
important when considering the right treatment regimen."
Subjects treated for 10 years with denosumab achieved an average
cumulative 10-year gain in BMD of 21.7 percent at the lumbar spine
and 9.2 percent at the total hip, compared to baseline in the
pivotal Phase 3 fracture study. Overall rates of AEs and serious
AEs were consistent with data reported previously in the extension
study. Yearly rates of new vertebral and nonvertebral fractures
remained low. During the seven years of the extension, 13 oral
events were confirmed as osteonecrosis of the jaw (ONJ) and two
events were confirmed as atypical femoral fracture by independent
adjudication committees. No atypical femoral fractures or ONJ cases
were reported in the original three-year core study.
"These 10-year findings from the final year of this open-label
extension study provide important additional data to the
significant body of evidence generated to inform long-term safety,
including more than 100 original publications and presentations
over the last seven years," said Sean E.
Harper, M.D., executive vice president of Research and
Development at Amgen. "Together, the evidence from this pivotal
Phase 3 fracture trial and its extension highlights the value of
Prolia in the treatment of women with postmenopausal osteoporosis
at high risk for fracture, as well as Amgen's commitment to
continued research in the field of osteoporosis."
About Osteoporosis
Osteoporosis affects many women
after menopause as their ability to form new bone cannot counter
balance the rate at which bone is being removed.1,2 This
bone loss leads to weakened bones over time, increasing the
potential for a break.3,4
About half of all women over age 50 will have an
osteoporosis-related fracture in their remaining
lifetime.5 Additionally, patients with a previous hip
fracture have a threefold greater risk of a subsequent fracture
within two years.6,7
The World Health Organization has officially declared
osteoporosis a public health crisis, while the International
Osteoporosis Foundation urges governments worldwide to make
osteoporosis a healthcare priority.
About Prolia® (denosumab)
Prolia is
the first approved therapy that specifically targets RANK Ligand,
an essential regulator of bone-removing cells (osteoclasts).
Prolia is approved in the U.S. 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 is also approved
for treatment to increase bone mass in men 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 is also indicated as a treatment to increase bone mass in
women at high risk for fracture receiving adjuvant aromatase
inhibitor therapy for breast cancer and in men at high risk for
fracture receiving androgen deprivation therapy for non-metastatic
prostate cancer.
Prolia is administered as a single subcutaneous injection of 60
mg once every six months. Please see the Important Safety
Information below.
Important Safety Information (U.S.)
Prolia is
contraindicated in patients with hypocalcemia. Preexisting
hypocalcemia must be corrected prior to initiating Prolia. Prolia
is contraindicated in women who are pregnant and may cause fetal
harm. Prolia is contraindicated in patients with a history of
systemic hypersensitivity to any component of the product.
Reactions have included anaphylaxis, facial swelling and
urticaria.
Prolia® contains the same active ingredient
(denosumab) found in XGEVA®. Patients receiving
Prolia® should not receive XGEVA®.
Clinically significant hypersensitivity including anaphylaxis
has been reported with Prolia®. Symptoms have included
hypotension, dyspnea, throat tightness, facial and upper airway
edema, pruritus, and urticaria. If an anaphylactic or other
clinically significant allergic reaction occurs, initiate
appropriate therapy and discontinue further use of
Prolia®.
Hypocalcemia may worsen with the use of
Prolia®, especially in patients with severe renal
impairment. In patients predisposed to hypocalcemia and
disturbances of mineral metabolism, clinical monitoring of calcium
and mineral levels is highly recommended within 14 days of
Prolia® injection. Adequately supplement all patients
with calcium and vitamin D.
ONJ, which can occur spontaneously, is generally associated with
tooth extraction and/or local infection with delayed healing, and
has been reported in patients receiving
Prolia®. An oral exam should be performed
by the prescriber prior to initiation of
Prolia®. A dental examination with
appropriate preventive dentistry is recommended prior to treatment
in patients with risk factors for ONJ such as invasive dental
procedures, diagnosis of cancer, concomitant therapies (e.g.
chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral
hygiene, and co-morbid disorders. Good oral hygiene practices
should be maintained during treatment with
Prolia®.
For patients requiring invasive dental procedures, clinical
judgment should guide the management plan of each patient.
Patients who are suspected of having or who develop ONJ should
receive care by a dentist or an oral surgeon. Extensive
dental surgery to treat ONJ may exacerbate the condition.
Discontinuation of Prolia® should be considered
based on individual benefit-risk assessment.
Atypical low-energy, or low trauma fractures of the shaft have
been reported in patients receiving Prolia®.
Causality has not been established as these fractures also occur in
osteoporotic patients who have not been treated with
anti-resorptive agents.
During Prolia® treatment, patients should be
advised to report new or unusual thigh, hip, or groin pain. Any
patient who presents with thigh or groin pain should be evaluated
to rule out an incomplete femur fracture. Interruption of
Prolia® therapy should be considered, pending a
risk/benefit assessment, on an individual basis.
In a clinical trial (N = 7808) in women with postmenopausal
osteoporosis, serious infections leading to hospitalization were
reported more frequently in the Prolia® group than in
the placebo group. Serious skin infections, as well as
infections of the abdomen, urinary tract and ear, were more
frequent in patients treated with Prolia®.
Endocarditis was also reported more frequently in
Prolia®-treated patients. The incidence of opportunistic
infections and the overall incidence of infections were similar
between the treatment groups. Advise patients to seek prompt
medical attention if they develop signs or symptoms of severe
infection, including cellulitis.
Patients on concomitant immunosuppressant agents or with
impaired immune systems may be at increased risk for serious
infections. In patients who develop serious infections while
on Prolia®, prescribers should assess the need
for continued Prolia® therapy.
In the same clinical trial in women with postmenopausal
osteoporosis, epidermal and dermal adverse events such as
dermatitis, eczema and rashes occurred at a significantly higher
rate with Prolia® compared to placebo. Most
of these events were not specific to the injection site.
Consider discontinuing Prolia® if severe symptoms
develop.
Severe and occasionally incapacitating bone, joint, and/or
muscle pain has been reported in patients taking
Prolia®. Consider discontinuing use if
severe symptoms develop.
In clinical trials in women with postmenopausal osteoporosis,
Prolia® resulted in significant suppression of
bone remodeling as evidenced by markers of bone turnover and bone
histomorphometry. The significance of these findings and the effect
of long-term treatment are unknown. Monitor patients for
consequences, including ONJ, atypical fractures, and delayed
fracture healing.
The most common adverse reactions (>5% and more common than
placebo) in women with postmenopausal osteoporosis are back pain,
pain in extremity, musculoskeletal pain, hypercholesterolemia, and
cystitis.
The most common adverse reactions (> 5% and more common than
placebo) in men with osteoporosis are back pain, arthralgia, and
nasopharyngitis. Pancreatitis has been reported with
Prolia®.
In women with postmenopausal osteoporosis, the overall incidence
of new malignancies was 4.3% in the placebo group and 4.8% in the
Prolia® groups. In men with osteoporosis, new
malignancies were reported in no patients in the placebo group and
4 (3.3%) patients in the Prolia® group. A causal
relationship to drug exposure has not been established. Denosumab
is a human monoclonal antibody. As with all therapeutic proteins,
there is potential for immunogenicity.
The Prolia Postmarketing Active Safety Surveillance Program is
available to collect information from prescribers on specific
adverse events. Please see https://www.proliasafety.com/ or
call 1-800-772-6436 for more information.
For more information, please see the Prolia Prescribing
Information, and Medication Guide.
About Amgen
Amgen is committed to unlocking the
potential of biology for patients suffering from serious illnesses
by discovering, developing, manufacturing and delivering innovative
human therapeutics. This approach begins by using tools like
advanced human genetics to unravel the complexities of disease and
understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages
its biologics manufacturing expertise to strive for solutions that
improve health outcomes and dramatically improve people's lives. A
biotechnology pioneer since 1980, Amgen has grown to be one of the
world's leading independent biotechnology companies, has reached
millions of patients around the world and is developing a pipeline
of medicines with breakaway potential.
For more information, visit www.amgen.com and 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,
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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 any subsequent 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
Oct. 12, 2015, 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
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CONTACT: Amgen, Thousand
Oaks
Kristen Davis, 805-447-3008
(media)
Kristen Neese, 805-313-8267
(media)
Arvind Sood, 805-447-1060
(investors)
References
1 U.S. Department of Health and Human Services,
Office of the Surgeon General. The 2004 Surgeon General's Report on
Bone Health and Osteoporosis: What It Means to You.
http://www.ncbi.nlm.nih.gov/books/NBK45513/pdf/Bookshelf_NBK45513.pdf.
Published October 14, 2004. Accessed
August 5, 2015.
2 National Osteoporosis Foundation. Clinician's Guide to
Prevention and Treatment of Osteoporosis.
http://nof.org/files/nof/public/content/file/344/upload/159.pdf.
Published January 2010. Accessed
August 5, 2015.
3 Chavassieux P, et al. Insights into material and
structural basis of bone fragility from diseases associated with
fractures: how determinants of the biomechanical properties of bone
are compromised by disease. Endocr Rev. 2007;28:151-164.
4 Seeman E, Delmas PD. Bone quality – the material and
structural basis of bone strength and fragility. N Engl J Med.
2006;354:2250-2261.
5 American Academy of Orthopedic Surgeons.
Osteoporosis and Bone Health.
http://www.aaos.org/news/aaosnow/may09/clinical8.asp. Accessed
August 5, 2015.
6 Colón-Emeric C, Kuchibhatla M, Pieper C, et al. The
contribution of hip fracture to risk of subsequent fractures: data
from two longitudinal studies. Osteoporos Int. 2003;14:879-883.
7 Lyles KW, Schenck AP, Colón-Emeric CS. Hip and other
osteoporotic fractures increase the risk of subsequent fractures in
nursing home residents. Osteoporos Int. 2008;19:1225-1233.
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