THOUSAND OAKS, Calif.,
July 31, 2017 /PRNewswire/
-- Amgen (NASDAQ:AMGN) today announced the submission of a
supplemental Biologics License Application (sBLA) to the U.S. Food
and Drug Administration (FDA) for Prolia® (denosumab)
for the treatment of patients with glucocorticoid-induced
osteoporosis (GIOP).The sBLA is based on a Phase 3 study evaluating
the safety and efficacy of Prolia compared with risedronate in
patients receiving glucocorticoid treatment.
Osteoporosis can be caused by glucocorticoid medications, which
are prescribed to treat inflammatory diseases. Within the first
three months of beginning glucocorticoid treatment, fracture risk
increases by up to 75 percent, with bone mineral density (BMD)
continuing to decline significantly in the months that
follow.1
"Glucocorticoid-induced osteoporosis can lead to weakened bones
and debilitating fractures," said Sean E.
Harper, M.D., executive vice president of Research and
Development at Amgen. "With this submission and future
approval, we look forward to bringing the benefits of Prolia to
patients living with this often overlooked and untreated form of
osteoporosis."
Results from the Phase 3 study included in the sBLA submission
showed that treatment with Prolia for 12 months led to
statistically significant greater gains in BMD at the lumbar spine
and total hip compared to risedronate, both in patients on
sustained glucocorticoid therapy and in those newly initiating
glucocorticoid therapy. Adverse events (AEs) and serious adverse
events (SAEs) were similar across treatment groups and consistent
with the known safety profile of Prolia.
About
Prolia® (denosumab)
Prolia is indicated 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 postmenopausal women with osteoporosis,
Prolia reduces the incidence of vertebral, nonvertebral, and hip
fractures.
Prolia is indicated 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 indicated as a treatment to increase bone mass in men
at high risk for fracture receiving androgen deprivation therapy
for nonmetastatic prostate cancer. In these patients Prolia also
reduced the incidence of vertebral fractures.
Prolia is indicated as a treatment to increase bone mass in
women at high risk for fracture receiving adjuvant aromatase
inhibitor therapy for breast cancer.
Important Safety Information
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.
Multiple Vertebral Fractures (MVF) Following Discontinuation
of Prolia Treatment
Following discontinuation of Prolia
treatment, fracture risk increases, including the risk of multiple
vertebral fractures. New vertebral fractures occurred as early as 7
months (on average 19 months) after the last dose of Prolia. Prior
vertebral fracture was a predictor of multiple vertebral fractures
after Prolia discontinuation. Evaluate an individual's benefit/risk
before initiating treatment with Prolia. If Prolia treatment is
discontinued, consider transitioning to an alternative
anti-resorptive therapy.
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.
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 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
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_____________________________________
1Weinstein
RS. Primer on the Metabolic Bone Diseases and Disorders of Mineral
Metabolism. ASBMR 8th Edition. 2013.
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