THOUSAND OAKS, Calif.,
Aug. 29, 2016 /PRNewswire/
-- Amgen (NASDAQ: AMGN) today announced positive top-line
results from the primary analysis conducted in a Phase 3
randomized, double-blind, double-dummy, active-controlled study
evaluating the safety and efficacy of Prolia®
(denosumab) compared with risedronate in patients receiving
glucocorticoid treatment. The study met all primary and secondary
endpoints at 12 months. The data showed that treatment with Prolia
for 12 months, compared to risedronate, led to significantly
greater gains in bone mineral density (BMD) at the lumbar spine and
total hip, both in patients receiving continuing glucocorticoid
therapy and in patients newly initiating glucocorticoid
therapy.
"The impact of glucocorticoid therapy on bone strength is
frequently underestimated, and often leads to increased bone loss
and ultimately, a fracture," said Sean E.
Harper, M.D., executive vice president of Research and
Development at Amgen. "We are excited that these data support the
potential for Prolia use in patients with glucocorticoid-induced
osteoporosis, the most common drug-induced form of the
disease."
Results from the glucocorticoid-induced osteoporosis (GIOP)
study showed that, in patients receiving continuing glucocorticoid
therapy, Prolia treatment led to greater gains in BMD, compared
with risedronate, both at the lumbar spine (4.4 percent vs. 2.3
percent, respectively) and total hip (2.1 percent vs. 0.6 percent,
respectively). Similarly, in patients newly initiating
glucocorticoid therapy, Prolia treatment led to greater increases
in BMD, compared with risedronate, both at the lumbar spine (3.8
percent vs. 0.8 percent, respectively) and total hip (1.7 percent
vs. 0.2 percent, respectively).
Adverse events (AEs) and serious adverse events (SAEs) were
similar across treatment groups and consistent with the known
safety profile of Prolia. No SAEs were reported with a subject
incidence of two percent or greater in either treatment
group.
This is a Phase 3 international, multi-center, randomized,
double-blind, double-dummy, active-controlled, parallel-group study
in men and women receiving oral glucocorticoid therapy. A total of
795 patients were enrolled in the 24-month study to evaluate the
safety and efficacy of treatment with Prolia 60 mg subcutaneously
every six months compared with oral risedronate 5 mg daily in two
patient subpopulations: 505 patients receiving continuing
glucocorticoid therapy (defined as patients receiving greater than
or equal to 7.5 mg daily prednisone or its equivalent for three
months or longer and planning to continue treatment for a total of
at least six months) and 290 patients newly initiating
glucocorticoid therapy (defined as patients receiving greater than
or equal to 7.5 mg daily prednisone or its equivalent for less than
three months and who are planning to continue treatment for a total
of at least six months).
Evaluation of the primary endpoint (the percent change from
baseline in lumbar spine BMD at 12 months, assessing
non-inferiority) and two secondary endpoints assessed at 12 months
(the percent change from baseline in lumbar spine and total hip
BMD, assessing superiority) was conducted; further analysis of
these results is ongoing and will be submitted to a future medical
conference and for publication. The study remains double-blinded
and ongoing for an additional 12 months.
About Glucocorticoid-induced Osteoporosis
Glucocorticoid-induced osteoporosis (GIOP), the most common form
of secondary osteoporosis, is caused by taking glucocorticoid
medicines which are commonly used to treat inflammatory
diseases.i Within the first three months of
glucocorticoid treatment, patient fracture risk increases up to 75
percent, although BMD will continue to decline significantly in the
months to follow.ii
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 and marketed in over 80 countries
worldwide.
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. In the U.S., 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 in the U.S.
Prolia is approved in the EU for the treatment of osteoporosis
in postmenopausal women and in men at increased risk of fractures.
Prolia is also approved in the EU for the treatment of bone loss
associated with hormone ablation in men with prostate cancer at
increased risk of fractures.
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.)
Contraindications
Prolia is contraindicated in patients with hypocalcemia.
Pre‐existing 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.
Same Active Ingredient
Prolia contains the same active ingredient (denosumab) found in
XGEVA®. Patients receiving Prolia should not receive
XGEVA®.
Hypersensitivity
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
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.
Osteonecrosis of the Jaw (ONJ)
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. The risk of ONJ may increase with duration
of exposure to 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 Femoral Fractures
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.
Serious Infections
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.
Dermatologic Adverse Reactions
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.
Musculoskeletal Pain
Severe and occasionally incapacitating bone, joint, and/or
muscle pain has been reported in patients taking Prolia. Consider
discontinuing use if severe symptoms develop.
Suppression of Bone Turnover
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 these consequences,
including ONJ, atypical fractures, and delayed fracture
healing.
Adverse Reactions
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 group. 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.
The most common (per patient incidence ≥ 10%) adverse reactions
reported with Prolia in patients with bone loss receiving ADT for
prostate cancer or adjuvant AI therapy for breast cancer are
arthralgia and back pain. Pain in extremity and musculoskeletal
pain have also been reported in clinical trials. Additionally, in
Prolia‐treated men with nonmetastatic prostate cancer receiving
ADT, a greater incidence of cataracts was observed.
Denosumab is a human monoclonal antibody. As with all
therapeutic proteins, there is potential for immunogenicity.
Prolia® Postmarketing Active Safety Surveillance
Program
The 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 Important Safety
Information, 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 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.
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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)
i Briot K, Roux C. Glucocorticoid-induced
osteoporosis. RMD Open. 2015;1:e000014.
ii Weinstein RS. Primer on the Metabolic Bone
Diseases and Disorders of Mineral Metabolism. ASBMR 8th Edition.
2013.
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