THOUSAND OAKS, Calif.,
Oct. 11, 2015 /PRNewswire/ -- Amgen
(NASDAQ:AMGN) today announced findings from a randomized,
double-blind, double-dummy, multicenter Phase 4 study showing that
Prolia® (denosumab) achieved greater gains in bone
mineral density (BMD) than the intravenous bisphosphonate
zoledronic acid in postmenopausal women with osteoporosis following
previous treatment with oral bisphosphonates. The findings were
presented today at the American Society for Bone and Mineral
Research (ASBMR) 2015 Annual Meeting in Seattle.
"Despite the availability of newer therapies like denosumab,
bisphosphonates are commonly used first-line to treat
osteoporosis," said lead investigator Paul
Miller, M.D., medical director of the Colorado Center for
Bone Research, Lakewood, Colo.
"Our findings showed that denosumab provides significantly greater
bone mineral density increases than zoledronic acid."
The 12-month study (NCT01732770) included 643 women 55 years or
older who had postmenopausal osteoporosis (BMD T-score –2.5 or less
at the lumbar spine, total hip, or femoral neck) and had been
taking oral bisphosphonate therapy for two or more years. The women
were randomized 1:1 to receive either subcutaneous denosumab (60
mg) every six months plus intravenous placebo once yearly
(denosumab group, 321 participants), or intravenous zoledronic acid
(5 mg) once yearly plus subcutaneous placebo every six months
(zoledronic acid group, 322 participants). The change from baseline
in lumbar spine BMD at 12 months – the primary endpoint – in the
denosumab group was significantly greater than that in the
zoledronic acid group: 3.2 percent vs. 1.1 percent, respectively
(p<0.0001).
The denosumab group also had significantly greater improvements
than the zoledronic acid group in secondary and exploratory study
endpoints, including BMD changes in the total hip (1.9 percent vs.
0.6 percent [p<0.0001]), femoral neck (1.2 percent vs.
-0.1 percent [p<0.0001]), and 1/3 radius (0.6 percent vs.
0 percent [p<0.0184]).
"These findings add to the evidence supporting Prolia as an
important therapeutic option for women with postmenopausal
osteoporosis, especially those who have failed bisphosphonate
treatment," said Sean E. Harper,
M.D., executive vice president of Research and Development at
Amgen. "Our continued research in this innovative antiresorptive
reinforces Amgen's commitment to bone biology and understanding the
value Prolia brings to treating osteoporosis in postmenopausal
women at high risk for fracture."
In the study, no new safety signals were identified. The two
study groups had similar incidences of overall adverse events
(AEs), serious AEs, AEs leading to discontinuation, and fatal AEs.
Three events consistent with the definition of atypical femoral
fracture were observed, including two in the denosumab group and
one in the zoledronic acid group. There were no cases of
osteonecrosis of the jaw (ONJ), hypocalcemia, or delayed fracture
healing.
About Osteoporosis
Excessive bone loss can lead to a
condition called osteoporosis, which significantly increases a
person's risk for fracture. Women specifically can lose up to 20
percent of their bone mass in the five to seven years after
menopause,1 and up to half of all women over the age of
50 will have an osteoporosis-related fracture in their
lifetime.2 Postmenopausal osteoporosis, the most common
form of the disease,3 is a condition that weakens bones
over time, making them thinner, more brittle, and more likely to
break.1
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 in the U.S. 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 percent 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 percent 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 percent in the placebo group and 4.8
percent in the Prolia® groups. In men with
osteoporosis, new malignancies were reported in no patients in the
placebo group and 4 (3.3 percent) 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 18007726436 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
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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. 11, 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
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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 American College of Preventative Medicine.
Osteoporosis: A Resource from the American College of
Preventative Medicine. 2009. Available
https://c.ymcdn.com/sites/www.acpm.org/resource/resmgr/timetools-files/osteoporosisclinicalreferenc.pdf.
Accessed on March 5, 2015.
2 National Osteoporosis Foundation. What Women Need
to Know. Available http://nof.org/articles/235. Accessed
March 5, 2015.
3 American Academy of Orthopaedic Surgeons. Position
Statement: Osteoporosis/Bone Health in Adults as a National Public
Health Priority. December 2014.
Available http://www.aaos.org/about/papers/position/1113.asp.
Accessed on March 5, 2015.
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