THOUSAND OAKS, Calif.,
Oct. 20, 2016 /PRNewswire/ -- Amgen
(NASDAQ:AMGN) today announced that a Phase 3 study evaluating
XGEVA® (denosumab) versus zoledronic acid met the
primary endpoint of non-inferiority (hazard ratio = 0.98, 95
percent CI, 0.85 - 1.14) in delaying the time to first
on-study skeletal-related event (SRE) in patients with multiple
myeloma. The secondary endpoints of superiority in delaying time to
first SRE and delaying time to first-and-subsequent SRE were not
met. The hazard ratio of XGEVA versus zoledronic acid for overall
survival was 0.90 (95 percent CI, 0.70 - 1.16).
Adverse events observed in patients treated with XGEVA were
generally consistent with the known safety profile of XGEVA. The
most common adverse events (greater than 25 percent) in the XGEVA
arm of the study were diarrhea and nausea.
"Bone complications like fracture, spinal cord compression and
radiation or surgery to bone are devastating for multiple myeloma
patients. Many of these patients suffer from renal impairment,
which has limited their treatment options," said Sean E. Harper, M.D., executive vice president
of Research and Development at Amgen. "XGEVA's unique mechanism of
action has the potential to prevent bone complications in multiple
myeloma patients regardless of their renal status, fulfilling an
important unmet medical need."
Detailed results will be submitted to a future medical
conference and for publication. The Company plans to submit these
data to regulatory authorities.
About '482 Study (NCT01345019)
The '482
study was an international, randomized, double-blind, multicenter
trial of XGEVA compared with zoledronic acid in the prevention of
bone complications in patients with newly diagnosed multiple
myeloma. In the study, a total of 1,718 patients (859 on each arm)
were randomized to receive either subcutaneous XGEVA 120 mg and
intravenous placebo every four weeks, or intravenous zoledronic
acid 4 mg (adjusted for renal function) and subcutaneous placebo
every four weeks. The primary endpoint of the study was
non-inferiority of XGEVA versus zoledronic acid with respect to
time to first on-study SRE (fracture, radiation to bone, surgery to
bone or spinal cord compression). Secondary endpoints included
superiority of XGEVA versus zoledronic acid with respect to time to
first on-study SRE and first-and-subsequent on-study SRE and
overall survival.The safety and tolerability of XGEVA were also
compared with zoledronic acid.
About Multiple Myeloma and Bone
Complications
Multiple myeloma is the second most common
hematologic cancer, and it develops in plasma cells located in the
bone marrow.1,2 Each year an estimated 114,000 new cases
of multiple myeloma are diagnosed worldwide, resulting in more than
80,000 deaths per year.2
Bone lesions frequently accompany multiple myeloma and can
increase the risk of bone complications.3,4
Approximately 75 percent of multiple myeloma patients are treated
for the prevention of bone complications.5 Preventing
bone complications is an important aspect of caring for patients
with multiple myeloma, because these events can cause significant
morbidity.6
About XGEVA® (denosumab)
XGEVA targets
the RANK ligand pathway to prevent the formation, function and
survival of osteoclasts, which break down bone. XGEVA is indicated
for the prevention of SREs in patients with bone metastases from
solid tumors and for treatment of 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 is also indicated in the U.S. for the treatment of
hypercalcemia of malignancy refractory to bisphosphonate therapy.
XGEVA is not indicated for the prevention of skeletal-related
events in patients with multiple myeloma.
U.S. 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, especially in the first weeks of
initiating therapy, 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.
An increased risk of hypocalcemia has been observed in clinical
trials of patients with increasing renal dysfunction, most commonly
with severe dysfunction (creatinine clearance less than 30
mL/minute and/or on dialysis), and with inadequate/no calcium
supplementation. Monitor calcium levels and calcium and vitamin D
intake.
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) has occurred in patients receiving XGEVA, manifesting as jaw
pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal
infection, toothache, gingival ulceration, or gingival
erosion. Persistent pain or slow healing of the mouth or jaw
after dental surgery may also be manifestations of ONJ. In clinical
trials in patients with osseous metastasis, the incidence of ONJ
was higher with longer duration of exposure.
Patients with a history of tooth extraction, poor oral hygiene,
or use of a dental appliance are at a greater risk to develop
ONJ. Other risk factors for the development of ONJ include
immunosuppressive therapy, treatment with angiogenesis inhibitors,
systemic corticosteroid, diabetes, and gingival infections.
Perform an oral examination and appropriate preventive dentistry
prior to the initiation of XGEVA and periodically during XGEVA
therapy. Advise patients regarding oral hygiene practices. Avoid
invasive dental procedures during treatment with
XGEVA. Consider temporarily interrupting XGEVA therapy if
an invasive dental procedure must be
performed.
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. 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. They may be bilateral and many
patients report prodromal pain in the affected area, usually
presenting as dull, aching thigh pain, weeks to months before a
complete fracture occurs. A number of reports note that patients
were also receiving treatment with glucocorticoids (e.g.
prednisone) at the time of fracture. 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. Based on findings in animals,
XGEVA is expected to result in adverse reproductive
effects. Advise females of reproductive potential to use
highly effective contraception during therapy, and for at least
five months after the last dose of XGEVA. Apprise the
patient of the potential hazard to a fetus if XGEVA is used during
pregnancy or if the patient becomes pregnant while patients are
exposed to 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 or www.xgeva.com for Full
U.S. Prescribing Information.
About Amgen's Commitment to Oncology
Amgen Oncology is
committed to helping patients take on some of the toughest cancers,
such as those that have been resistant to drugs, those that
progress rapidly through the body and those where limited treatment
options exist. Amgen's supportive care treatments help patients
combat certain side effects of strong chemotherapy, and our
targeted medicines and immunotherapies focus on more than a dozen
different malignancies, ranging from blood cancers to solid tumors.
With decades of experience providing therapies for cancer patients,
Amgen continues to grow its portfolio of innovative and biosimilar
oncology medicines.
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.
Forward-Looking Statements
This news release contains
forward-looking statements that are based on the current
expectations and beliefs of Amgen. All statements, other than
statements of historical fact, are statements that could be deemed
forward-looking statements, including estimates of revenues,
operating margins, capital expenditures, cash, other financial
metrics, expected legal, arbitration, political, regulatory or
clinical results or practices, customer and prescriber patterns or
practices, reimbursement activities and outcomes and other such
estimates and results. Forward-looking statements involve
significant risks and uncertainties, including those discussed
below and more fully described in the Securities and Exchange
Commission reports filed by Amgen, including our most recent annual
report on Form 10-K and any subsequent periodic reports on Form
10-Q and Form 8-K. Unless otherwise noted, Amgen is providing this
information as of the date of this news release and does not
undertake any obligation to update any forward-looking statements
contained in this document as a result of new information, future
events or otherwise.
No forward-looking statement can be guaranteed and actual
results may differ materially from those we project. Discovery
or identification of new product candidates or development of new
indications for existing products cannot be guaranteed and movement
from concept to product is uncertain; consequently, there can be no
guarantee that any particular product candidate or development of a
new indication for an existing product will be successful and
become a commercial product. Further, preclinical results do not
guarantee safe and effective performance of product candidates in
humans. The complexity of the human body cannot be perfectly, or
sometimes, even adequately modeled by computer or cell culture
systems or animal models. The length of time that it takes for us
to complete clinical trials and obtain regulatory approval for
product marketing has in the past varied and we expect similar
variability in the future. Even when clinical trials are
successful, regulatory authorities may question the sufficiency for
approval of the trial endpoints we have selected. We develop
product candidates internally and through licensing collaborations,
partnerships and joint ventures. Product candidates that are
derived from relationships may be subject to disputes between the
parties or may prove to be not as effective or as safe as we may
have believed at the time of entering into such relationship. Also,
we or others could identify safety, side effects or manufacturing
problems with our products after they are on the market.
Our results may be affected by our ability to successfully
market both new and existing products domestically and
internationally, clinical and regulatory developments involving
current and future products, sales growth of recently launched
products, competition from other products including biosimilars,
difficulties or delays in manufacturing our products and global
economic conditions. In addition, sales of our products are
affected by pricing pressure, political and public scrutiny and
reimbursement policies imposed by third-party payers, including
governments, private insurance plans and managed care providers and
may be affected by regulatory, clinical and guideline developments
and domestic and international trends toward managed care and
healthcare cost containment. Furthermore, our research, testing,
pricing, marketing and other operations are subject to extensive
regulation by domestic and foreign government regulatory
authorities. We or others could identify safety, side effects or
manufacturing problems with our products after they are on the
market. Our business may be impacted by government investigations,
litigation and product liability claims. In addition, our business
may be impacted by the adoption of new tax legislation or exposure
to additional tax liabilities. If we fail to meet the compliance
obligations in the corporate integrity agreement between us and the
U.S. government, we could become subject to significant sanctions.
Further, while we routinely obtain patents for our products and
technology, the protection offered by our patents and patent
applications may be challenged, invalidated or circumvented by our
competitors, or we may fail to prevail in present and future
intellectual property litigation. We perform a substantial amount
of our commercial manufacturing activities at a few key facilities
and also depend on third parties for a portion of our manufacturing
activities, and limits on supply may constrain sales of certain of
our current products and product candidate development. In
addition, we compete with other companies with respect to many of
our marketed products as well as for the discovery and development
of new products. Further, some raw materials, medical devices and
component parts for our products are supplied by sole third-party
suppliers. The discovery of significant problems with a product
similar to one of our products that implicate an entire class of
products could have a material adverse effect on sales of the
affected products and on our business and results of operations.
Our efforts to acquire other companies or products and to integrate
the operations of companies we have acquired may not be successful.
We may not be able to access the capital and credit markets on
terms that are favorable to us, or at all. We are increasingly
dependent on information technology systems, infrastructure and
data security. Our stock price is volatile and may be affected by a
number of events. Our business performance could affect or limit
the ability of our Board of Directors to declare a dividend or our
ability to pay a dividend or repurchase our common stock.
The scientific information discussed in this news release
relating to new indications for our products is preliminary and
investigative and is not part of the labeling approved by the U.S.
Food and Drug Administration for the products. The products are not
approved for the investigational use(s) discussed in this news
release, and no conclusions can or should be drawn regarding the
safety or effectiveness of the products for these uses.
CONTACT: Amgen, Thousand
Oaks
Kristen Davis, 805-447-3008
(Media)
Kristen Neese, 805-313-8267
(Media)
Arvind Sood, 805-447-1060
(Investors)
References:
- Multiple Myeloma Research Foundation. What is Multiple Myeloma?
https://www.themmrf.org/multiple-myeloma/what-is-multiple-myeloma/.
Accessed Oct. 7, 2016.
- Globocan 2012: Estimated Cancer Incidence, Mortality and
Prevalence in 2012.
http://globocan.iarc.fr/Pages/fact_sheets_population.aspx. Accessed
Oct. 7, 2016.
- Roodman GD. Pathogenesis of myeloma bone disease. Leukemia.
2009;23(3):435–441.
- Terpos E, et al. International Myeloma Working Group
recommendations for the treatment of multiple myeloma-related bone
disease. J Clin Oncol. 2013;31(18):2347-57.
- Amgen data on file.
- Drake MT. Bone disease in multiple myeloma. Oncology
(Williston Park). 2009;23(14
Suppl 5):28-32.
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