FDA Approves Amgen's XGEVA® (denosumab) For The Treatment Of Giant Cell Tumor Of Bone

FDA Approves Amgen's XGEVA® (denosumab) For The Treatment Of Giant Cell Tumor
                                   Of Bone

XGEVA Becomes First FDA-Approved Treatment for This Rare Disease

PR Newswire

THOUSAND OAKS, Calif., June 13, 2013

THOUSAND OAKS, Calif., June 13, 2013 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today
announced that the U.S. Food and Drug Administration (FDA) has approved a new
indication for XGEVA^® (denosumab) for the treatment of adults and skeletally
mature adolescents with giant cell tumor of bone (GCTB) that is unresectable
or where surgical resection is likely to result in severe morbidity. XGEVA was
approved following a priority review by the FDA, a designation reserved for
drugs that offer major advances in treatment, or provide a treatment where no
adequate therapy exists.

GCTB typically affects individuals between the ages of 20 to 40. The disease
is characterized by a bone destructive tumor that often results in fractures.
When untreated, it often results in complete destruction of the affected bone,
leading to bone fracture, joint dysfunction, deformity or amputation.

The approval of XGEVA is based on positive results from two open-label trials
that enrolled patients with GCTB that was either recurrent, unresectable, or
for which planned surgery was likely to result in severe morbidity. The
overall objective response rate of the 187 patients evaluated was 25 percent.
The estimated median time to response was three months. In the 47 patients
with an objective response, 51 percent (24/47) had a duration of response
lasting at least eight months. Three patients experienced disease progression
following an objective response.

The safety profile of XGEVA in patients with GCTB was similar to that reported
in studies of patients with bone metastases, and also appeared to be similar
in skeletally mature adolescents and adults. Safety data was evaluated in 304
patients with GCTB who received at least one dose of XGEVA. Of these
patients, 145 were treated for at least one year. The most common adverse
reactions were arthralgia, headache, nausea, back pain, fatigue, and pain in
the extremity. The most common serious adverse reactions were osteonecrosis
of the jaw and osteomyelitis.

For patients with GCTB, XGEVA is administered as a subcutaneous injection (120
mg) every four weeks with additional 120 mg doses on days eight and 15 of the
first month of therapy.

"With today's XGEVA FDA approval, Amgen can offer a much needed treatment
option to patients who suffer from giant cell tumor of bone that cannot be
adequately treated with surgery," said Sean E. Harper, M.D., executive vice
president of Research and Development at Amgen. "Advances in our understanding
of the underlying biology of this rare disorder have allowed Amgen to generate
compelling clinical evidence to address the medical needs of patients and
their healthcare providers."

XGEVA binds to RANK Ligand (RANKL), a protein essential for the formation,
function and survival of osteoclasts - the cells responsible for bone
resorption. Giant cell tumors of bone consist of stromal cells expressing
RANKL and osteoclast-like giant cells expressing RANK receptor. Signaling
through the RANK receptor contributes to osteolysis and tumor growth. XGEVA
prevents RANKL from activating its receptor, RANK, on the surface of
osteoclasts, their precursors and osteoclast-like giant cells.

About Giant Cell Tumor of Bone
GCTB is a locally aggressive, benign tumor afflicting younger adults between
the ages 20 to 40. It is estimated that there are approximately 300-800 new
cases of GCTB annually in the U.S. GCTB is unresectable in approximately 18-20
percent of cases.

Most tumors occur in the long bones of the body, often around joints, but can
also spread to the lungs in rare cases. Although giant cell tumors are slow
growing, patients can experience severe bone pain, swelling, loss of mobility
and pathologic fracture. Historically, there have been no approved therapies
for GCTB. Surgery is the main treatment option for patients with resectable
GCTB; however, surgery, such as amputation, may be associated with significant
morbidity. These tumors also have a higher recurrence rate within the first
three years of surgical intervention. When tumors recur, they become more
difficult to treat and more likely to spread to other parts of the body.

About XGEVA
XGEVA was approved by the FDA for the prevention of skeletal-related events
(SREs) in patients with bone metastases from solid tumors in 2010. XGEVA is
not indicated for the prevention of SREs in patients with multiple myeloma. In
clinical trials, XGEVA demonstrated a clinically meaningful improvement
compared to the previous standard of care in preventing these bone
complications.

In 2013, XGEVA was approved by the FDA as the first and only treatment for
adults and skeletally mature adolescents with GCTB that is unresectable or
where surgical resection is likely to result in severe morbidity.

XGEVA Important Safety Information
Hypersensitivity
XGEVA is contraindicated in patients with clinically significant
hypersensitivity to any component of the product.

Hypocalcemia
XGEVA can cause severe symptomatic hypocalcemia, and fatal cases have been
reported. Correct pre-existing hypocalcemia prior to XGEVA treatment. Monitor
calcium levels and administer calcium, magnesium, and vitamin D as necessary.
Advise patients to contact a healthcare professional for symptoms of
hypocalcemia.

Osteonecrosis of the Jaw (ONJ)
Osteonecrosis of the jaw (ONJ) can occur in patients receiving XGEVA. Patients
who are suspected of having or who develop ONJ while on XGEVA should receive
care by a dentist or an oral surgeon. In these patients, extensive dental
surgery to treat ONJ may exacerbate the condition.

Atypical Subtrochanteric and Diaphyseal Femoral Fracture
Atypical femoral fracture has been reported with XGEVA. Causality has not been
established as these fractures also occur in osteoporotic patients who have
not been treated with anti-resorptive agents. A number of reports note that
patients were also receiving treatment with glucocorticoids at the time of
fracture. Any patient who presents with thigh or groin pain should be
suspected of having an atypical fracture and should be evaluated to rule out
an incomplete femur fracture. Interruption of XGEVA therapy should be
considered, pending a risk/benefit assessment, on an individual basis.

Embryo-Fetal Toxicity
XGEVA can cause fetal harm when administered to a pregnant woman. Advise
females of reproductive potential to use highly effective contraception during
therapy, and for at least 5 months after with the last dose of XGEVA.

Adverse Reactions
The most common adverse reactions in patients receiving XGEVA with bone
metastasis from solid tumors were fatigue/asthenia, hypophosphatemia, and
nausea. The most common serious adverse reaction was dyspnea.

The most common adverse reactions in patients receiving XGEVA for giant cell
tumor of bone were arthralgia, headache, nausea, back pain, fatigue, and pain
in extremity. The most common serious adverse reactions were osteonecrosis of
the jaw and osteomyelitis.

Please visit www.amgen.com for full prescribing information.

About Amgen
Amgen discovers, develops, manufactures and delivers innovative human
therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first
companies to realize the new science's promise by bringing safe, effective
medicines from lab to manufacturing plant to patient. Amgen therapeutics have
changed the practice of medicine, helping people around the world in the fight
against serious illnesses. With a deep and broad pipeline of potential new
medicines, Amgen remains committed to advancing science to dramatically
improve people's lives. For more information, visit www.amgen.com and follow
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CONTACT: Amgen, Thousand Oaks
Christine Regan, 805-447-5476 (media)
Arvind Sood, 805-447-1060 (investors)

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