THOUSAND OAKS, Calif.,
Oct. 9, 2017 /PRNewswire/ -- Amgen
(NASDAQ:AMGN) today announced that the U.S. Food and Drug
Administration (FDA) has accepted for review the supplemental
Biologics License Application (sBLA) for Prolia®
(denosumab) for the treatment of patients with
glucocorticoid-induced osteoporosis (GIOP). The sBLA, which was
submitted on July 28, 2017, is based
on a Phase 3 study evaluating Prolia compared with risedronate in
patients receiving glucocorticoid treatment. The FDA has set a
Prescription Drug User Fee Act (PDUFA) action date of May 28, 2018.
Glucocorticoid medications, which are used to treat many
inflammatory conditions, can cause significant side effects,
including bone loss. GIOP is the most common form of secondary
osteoporosis1, and it is estimated that one percent of
the U.S. population is treated long-term with glucocorticoid
medications.2 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.3
"We believe that Prolia can address a critical treatment need
for patients with glucocorticoid-induced osteoporosis, which is the
most common drug-induced form of the disease," said Sean E. Harper, M.D., executive vice president
of Research and Development at Amgen. "We will continue to work
closely with the FDA as they review our application and look
forward to expanding Prolia's benefits to patients with this
serious condition that is often underestimated and untreated."
The sBLA is supported by a Phase 3 randomized, double-blind,
double-dummy, active-controlled study evaluating the safety and
efficacy of Prolia compared with risedronate in patients receiving
glucocorticoid treatment.4 The study included two
patient groups: those receiving continuing glucocorticoid therapy
and those newly initiating glucocorticoid therapy. The study met
the primary endpoint (percent change from baseline in lumbar spine
BMD at 12 months, assessing non-inferiority) and all secondary
endpoints assessed at 12 months (the percent changes from baseline
in lumbar spine and total hip BMD, assessing superiority). Study
results 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 versus 2.3 percent, respectively) and total hip (2.1
percent versus 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 versus 0.8 percent, respectively) and
total hip (1.7 percent versus 0.2 percent, respectively).
Adverse events and serious adverse events were similar between
treatment groups and consistent with the known safety profile of
Prolia. No serious adverse events were reported with a subject
incidence of two percent or greater in either treatment group.
About Glucocorticoid-Induced Osteoporosis (GIOP)
GIOP
is the most common form of secondary osteoporosis1, and
it is estimated that one percent of the U.S. population is treated
long-term with glucocorticoid medications.2 While the
number of GIOP patients that overlap with osteoporosis patients is
not clear, the most frequent chronic inflammatory diseases
associated with long-term glucocorticoid use are chronic
obstructive pulmonary disorder (COPD), asthma and rheumatoid
arthritis.5 The exact prevalence is not clear due
to overlap with the osteoporosis population. More than 10
percent of patients who receive long-term glucocorticoid treatment
are diagnosed with a clinical fracture, and 30 to 40 percent have
radiographic evidence of vertebral fractures.6,7
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 (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.
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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