THOUSAND OAKS, Calif.,
Dec. 8, 2014 /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 hypercalcemia of
malignancy (HCM) refractory to bisphosphonate therapy. XGEVA was
approved and granted Orphan Drug Designation by the FDA, which is
reserved for drugs that are intended for the treatment of rare
diseases affecting fewer than 200,000 people in the U.S.
HCM is a serious complication in patients with advanced cancer,
including those with hematologic malignancies, and indicates poor
prognosis.1,2 The condition results from cancer-driven
increases in bone resorption, and if untreated, can lead to renal
failure, progressive mental impairment, coma and
death.1-3
"Our continued study of XGEVA reinforces Amgen's ongoing
commitment to address the unmet needs of cancer patients," said
Sean E. Harper, M.D., executive vice
president of Research and Development at Amgen. "This latest FDA
approval for XGEVA provides an important new therapeutic option for
patients with a rare condition that cannot be resolved with
bisphosphonate therapy."
The approval of XGEVA is based on positive results from an
open-label, single-arm study, which enrolled patients with advanced
cancer and persistent hypercalcemia after recent bisphosphonate
treatment. The primary endpoint was the proportion of patients with
a response, defined as albumin-corrected serum calcium (CSC)
<11.5 mg/dL (2.9 mmol/L; Common Terminology for Adverse Events
[CTCAE] grade <1) within 10 days after the first dose of XGEVA.
Secondary endpoints included the proportion of patients who
experienced a complete response (defined as CSC <10.8 mg/dL [2.7
mmol/L]) by day 10, time to response and response duration (defined
as the number of days from the first occurrence of CSC <11.5
mg/dL). The study achieved its primary endpoint with a response
rate at day 10 of 63.6 percent in the 33 patients evaluated. The
overall complete response rate was 63.6 percent. The estimated
median time to response (CSC <11.5 mg/dL) was nine days, and the
median duration of response was 104 days.4,5
The most common adverse reactions in patients receiving XGEVA
for hypercalcemia of malignancy were nausea, dyspnea, decreased
appetite, headache, peripheral edema, vomiting, anemia,
constipation and diarrhea.5
For patients with HCM, XGEVA is administered as a subcutaneous
injection (120 mg) every four weeks with additional doses of 120 mg
on days eight and 15 of the first month of therapy.5
XGEVA binds to RANK Ligand (RANKL), a protein essential for the
formation, function and survival of osteoclasts, the cells
responsible for bone resorption, thereby modulating calcium release
from bone. XGEVA prevents RANKL from activating its receptor, RANK,
on the surface of osteoclasts, thereby decreasing bone destruction
and calcium release.5
About Hypercalcemia of Malignancy
Hypercalcemia of malignancy (HCM) is a serious complication in
patients with advanced cancer, including those with hematological
malignancies.1 In 2012, the estimated prevalence of HCM
in cancer patients in the U.S. was 2.7 percent.6
HCM is indicative of poor prognosis and occurs most often in
patients with squamous cell cancer (e.g., lung cancer, head and
neck cancer), breast cancer, kidney cancer, myeloma and
lymphoma.1,2,7 HCM results from cancer-driven increases
in bone resorption, and, if untreated, can lead to renal failure,
progressive mental impairment, coma and death.1-3
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 SREs. In
2013, XGEVA was approved by the FDA as the first-and-only treatment
for adults and skeletally mature adolescents with giant cell tumor
of bone that is unresectable or where surgical resection is likely
to result in severe morbidity.
XGEVA Important Safety Information
Hypocalcemia
Pre-existing hypocalcemia must be corrected prior to initiating
therapy with XGEVA. XGEVA can cause severe symptomatic
hypocalcemia, and fatal cases have been reported. Monitor calcium
levels and administer calcium, magnesium, and vitamin D as
necessary. Monitor levels more frequently when XGEVA is
administered with other drugs that can also lower calcium levels.
Advise patients to contact a healthcare professional for symptoms
of hypocalcemia.
Hypersensitivity
XGEVA is contraindicated in patients with known clinically
significant hypersensitivity to XGEVA, including
anaphylaxis that has been reported with use of XGEVA. If an
anaphylactic or other clinically significant allergic reaction
occurs, initiate appropriate therapy and discontinue XGEVA therapy
permanently.
Drug Products with Same Active Ingredient
Patients receiving XGEVA should not take Prolia®
(denosumab).
Osteonecrosis of the Jaw
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. In clinical trials in patients with
osseous metastasis, the incidence of ONJ was higher with longer
duration of exposure.
Atypical Subtrochanteric and Diaphyseal Femoral
Fracture
Atypical femoral fracture has been reported with XGEVA. These
fractures can occur anywhere in the femoral shaft from just below
the lesser trochanter to above the supracondylar flare and are
transverse or short oblique in orientation without evidence of
comminution.
Atypical femoral fractures most commonly occur with minimal or
no trauma to the affected area. During XGEVA treatment, patients
should be advised to report new or unusual thigh, hip, or groin
pain. Patient presenting with an atypical femur fracture should
also be assessed for symptoms and signs of fracture in the
contralateral limb. 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 five
months after 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.
The most common adverse reactions resulting in discontinuation of
XGEVA were osteonecrosis of the jaw and tooth abscess or tooth
infection.
The most common adverse reactions in patients receiving XGEVA
for hypercalcemia of malignancy were nausea, dyspnea, decreased
appetite, headache, peripheral edema, vomiting, anemia,
constipation, and diarrhea.
Denosumab is also marketed as Prolia® in other
indications.
Please visit www.amgen.com for Full Prescribing Information.
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 the world's
largest independent biotechnology company, 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 the current expectations and beliefs of Amgen Inc. and its
subsidiaries (Amgen, we or us) and are subject to a number of
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including Amgen Inc.'s most recent annual report on Form 10-K and
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refer to Amgen Inc.'s most recent Forms 10-K, 10-Q and 8-K for
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related to our business. Unless otherwise noted, Amgen is providing
this information as of Dec. 8, 2014,
and expressly disclaims any duty to update information contained in
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No forward-looking statement can be guaranteed and actual
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identification of new product candidates or development of new
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CONTACT: Amgen, Thousand
Oaks
Kristen Davis, 805-447-3008
(media)
Trish Hawkins, 805-447-5631
(media)
Arvind Sood, 805-447-1060
(investors)
References
- Ralston SH. Cancer-associated hypercalcemia: morbidity and
mortality. Annals of Int Med. 1990;112:499-504.
- Stewart AF. Clinical practice. Hypercalcemia associated with
cancer. N Engl J Med. 2005;352(4):373-379.
- Coleman RE. Clinical features of metastatic bone disease and
risk of skeletal morbidity. Clin Cancer
Res. 2006;12(suppl 20):6243s-6249s.
- Hu MI. Denosumab for treatment of hypercalcemia of malignancy.
J Clin Endocrinol Metab. 2014; 99(9):3144–3152
- XGEVA® (denosumab) prescribing information. Amgen.
- Gastanaga V, Jain R, Pirolli M, et al. Prevalence of
hypercalcemia of malignancy in the United
States: projection methods using oncology electronic health
records (EHR). Eur J Cancer. 2013;49:S1–S1028, Abstract 1415, p.
25.
- Major P, Lortholary A, Hon J, et al. Zoledronic acid is
superior to pamidronate in the treatment of hypercalcemia of
malignancy: a pooled analysis of two randomized, controlled
clinical trials. J Clin Oncol. 2001;19(2):558-567.
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