FDA Approves Nplate(TM) for Long-Term Treatment of Adult Chronic ITP
First and Only Approved Platelet Producer Represents New Treatment Approach for Serious Chronic Autoimmune Disorder
Amgen to Launch Nplate(TM) NEXUS Program to Provide Treatment Access and Patient Support Programs
THOUSAND OAKS, Calif., Aug 22, 2008 (BUSINESS WIRE) -- Amgen Inc. (NASDAQ: AMGN) today announced that the United States
(U.S.) Food and Drug Administration (FDA) has approved Nplate(TM)
(romiplostim), the first and only platelet producer for the treatment
of thrombocytopenia in splenectomized (spleen removed) and
non-splenectomized adults with chronic immune thrombocytopenic purpura
(ITP). Nplate, the first FDA-approved peptibody protein, works by
raising and sustaining platelet counts, representing a novel approach
for the long-term treatment of this chronic disease.
Chronic ITP is a serious autoimmune disorder characterized by low
platelet counts in the blood (thrombocytopenia), which can lead to
serious bleeding events. Recognized as an orphan disease, chronic ITP
affects an estimated 60,000 adult patients in the U.S. and is
considered an unmet need by the FDA.
"Until now, patients suffering from chronic ITP have had limited
available treatment options, many of which are often unsuitable for
long-term use due to side effects and tolerability issues," said David
J. Kuter, M.D., Chief of Hematology, Massachusetts General Hospital,
Boston. "Nplate represents the first long-term treatment for adult
chronic ITP patients, providing a new treatment approach for this
The FDA approval of Nplate was based on efficacy and safety
results from two pivotal Phase 3 studies of adult patients with
chronic ITP, including both splenectomized and non-splenectomized
patients. The overall response rate for Nplate was 83 percent
(n=69/83, p less than 0.0001) of treated splenectomized and
non-splenectomized patients, and platelet counts were raised and
sustained in these six month studies. Additionally, patients treated
with Nplate were able to reduce or discontinue their use of
concomitant ITP medications and emergency medications (i.e.,
corticosteroids, IVIG, Win-Rho, Anti-D therapy).
Specifically, in the Phase 3 studies, non-splenectomized patients
had an 88 percent (n=36/41, p less than 0.0001) overall platelet
response and splenectomized patients had a 79 percent (n=33/42, p less
than 0.0001) overall platelet response rate. Combined data from both
trials shows clinically relevant bleeding events were significantly
reduced by half in patients treated with Nplate compared to placebo
(15 percent vs. 34 percent, p=0.018). Amgen continues to study the
long-term efficacy and safety of Nplate for which there is more than
three years of follow up safety and efficacy data.
"For those suffering from ITP, the daily fear of experiencing a
serious bleeding episode can be emotionally stressful and extremely
difficult for both patients and their families. We welcome the
addition of new treatment options which offer new hope for the
treatment of this serious disease," said Craig Conway, executive
director of the Platelet Disorder Support Association.
In addition to improved clinical benefits, described in the FDA
labeling, Amgen believes Nplate offers patients a positive net health
benefit with fewer hospitalizations from bleeding events, as well as
reduced need for emergency medications (IVIG and Win-Rho). Amgen
expects the total costs of care for chronic ITP patients managed with
Nplate to be less than or comparable to the total costs of care with
standard treatment regimens.
Amgen also announced it will launch the Nplate(TM) NEXUS (Network
of EXperts Understanding and Supporting Nplate(TM) and Patients)
Program, a multi-faceted program designed to provide comprehensive
access, support and education for chronic ITP patients, their
caregivers and healthcare providers. The Nplate(TM) NEXUS Program is
part of the Risk Evaluation and Mitigation Strategy (REMS) developed
by Amgen in partnership with the FDA to assure safe use of Nplate
while minimizing risk. The program will facilitate appropriate use of
Nplate, provide patient support through education and resources and
help with ongoing follow up through safety data collection.
Through the Nplate(TM) NEXUS Program, eligible patients who are
uninsured, underinsured, or unable to afford their insurance
co-payments may be able to receive reimbursement support and other
assistance from Amgen. For example, one such program helps cover up to
50 percent of an eligible, commercially-insured patient's co-payments
for Nplate. Recognizing that some patients may not have healthcare
coverage, Amgen continues to offer another program for all of its
innovative products, including Nplate, which provides product free of
charge to eligible, low-income patients without insurance.
"Amgen is committed to advancing the discovery and development of
new therapies for grievous illnesses where there is unmet medical
need," said Roger M. Perlmutter, M.D., Ph.D., executive vice president
of Research and Development at Amgen. "The FDA approval of Nplate is
the result of more than 15 years of research and represents an
important biotechnology milestone as it is the first FDA-approved
peptibody protein, an innovative platform for delivering targeted
Nplate was also approved for ITP by Australia's Therapeutic Goods
Administration (TGA) in July 2008. Amgen has filed for regulatory
approval of Nplate in the European Union (EU), Canada, and Switzerland
and these applications are currently under review. Nplate has also
received orphan designation for ITP in the EU (2005), Switzerland
(2005) and Japan (2006).
More information about the Nplate(TM) NEXUS Program is available
by calling 1-877-NPLATE1 (1-877-675-2831), or by visiting
About Adult ITP
Platelets are blood cells needed to prevent bleeding. Low platelet
counts leave adult ITP patients open to sudden serious bleeding
events, making it impossible to arrest blood flow. The risk for
serious bleeding events increases when platelet counts drop to less
than 30,000 platelets per microliter.
There are limited approved treatments (i.e., corticosteroids,
immunoglobulins) or surgical therapy (removal of the spleen) available
to adult patients with chronic ITP. Currently, there are 140,000
treated chronic ITP patients in the U.S. and Europe. ITP affects about
twice as many adult women as men.
With ITP, platelets are destroyed by the patient's own immune
system. ITP has historically been considered a disease of platelet
destruction. However, recent data also suggest that the body's natural
platelet production processes are unable to compensate for low levels
of platelets in the blood. Increasing the rate of platelet production
may address low platelet levels associated with ITP.
Nplate, Amgen's first peptibody protein, is a novel engineered
therapeutic fusion protein with attributes of both peptides and
antibodies, but is distinct from each. Nplate works similarly to
thrombopoietin (TPO), a natural protein in the body. Nplate stimulates
the TPO receptor, which is necessary for growth and maturation of bone
marrow cells that produce platelets.
Important Safety Information
Serious adverse reactions associated with Nplate in clinical
studies were bone marrow reticulin deposition and worsening
thrombocytopenia after Nplate discontinuation.
Bone Marrow Reticulin Formation and Risk for Bone Marrow Fibrosis
-- Nplate administration increases the risk for development or
progression of reticulin fiber deposition within the bone
-- In clinical studies, Nplate was discontinued in four of the
271 patients because of bone marrow reticulin deposition. Six
additional patients had reticulin observed upon bone marrow
biopsy. All 10 patients with bone marrow reticulin deposition
had received Nplate doses greater than or equal to 5 mcg/kg,
and 6 received doses greater than or equal to 10 mcg/kg.
-- Progression to marrow fibrosis with cytopenias was not
reported in the controlled clinical studies. In the extension
study, one patient with ITP and hemolytic anemia developed
marrow fibrosis with collagen during Nplate therapy.
-- Clinical studies have not excluded a risk of bone marrow
fibrosis with cytopenias.
-- Prior to initiation of Nplate examine the peripheral blood
smear closely to establish a baseline level of cellular
morphologic abnormalities. Following identification of a
stable Nplate dose, examine peripheral blood smears and CBCs
monthly for new or worsening morphological abnormalities (eg,
teardrop and nucleated red blood cells, immature white blood
cells) or cytopenia(s).
-- If the patient develops new or worsening morphological
abnormalities or cytopenia(s), discontinue treatment with
Nplate and consider a bone marrow biopsy, including staining
Worsened Thrombocytopenia After Cessation of Nplate
-- Discontinuation of Nplate may result in thrombocytopenia of
greater severity than was present prior to Nplate therapy.
This worsened thrombocytopenia may increase the patient's risk
of bleeding, particularly if Nplate is discontinued while the
patient is on anticoagulants or antiplatelet agents.
-- In clinical studies of patients with chronic ITP who had
Nplate discontinued, four of 57 patients developed
thrombocytopenia of greater severity than was present prior to
-- This worsened thrombocytopenia resolved within 14 days.
-- Following discontinuation of Nplate, obtain weekly CBCs,
including platelet counts, for at least two weeks and consider
alternative treatments for worsening thrombocytopenia,
according to current treatment guidelines.
-- Thrombotic/thromboembolic complications may result from
excessive increases in platelet counts. Excessive doses of
Nplate or medication errors that result in excessive Nplate
doses may increase platelet counts to a level that produces
thrombotic/thromboembolic complications. In controlled
clinical studies, the incidence of thrombotic/thromboembolic
complications was similar between Nplate and placebo.
-- To minimize the risk for thrombotic/thromboembolic
complications, do not use Nplate in an attempt to "normalize"
platelet counts. Follow the dose adjustment guidelines to
achieve and maintain a platelet count of greater than or equal
to 50 x 10 to the ninth/L.
Lack or Loss of Response to Nplate
-- Hyporesponsiveness or failure to maintain a platelet response
with Nplate should prompt a search for causative factors,
including neutralizing antibodies to Nplate or bone marrow
-- To detect antibody formation, submit blood samples to Amgen
(1-800-772-6436). Amgen will assay these samples for
antibodies to Nplate and thrombopoietin (TPO).
-- Discontinue Nplate if the platelet count does not increase to
a level sufficient to avoid clinically important bleeding
after 4 weeks at the highest weekly dose of 10 mcg/kg.
Hematological Malignancies and Progression of Malignancy in
Patients with a Pre-existing Hematological Malignancy or
Myelodysplastic Syndrome (MDS)
-- Nplate stimulation of the TPO receptor on the surface of
hematopoietic cells may increase the risk for hematologic
malignancies. In controlled clinical studies among patients
with chronic ITP, the incidence of hematologic malignancy was
low and similar between Nplate and placebo.
-- In a separate single-arm clinical study of 44 patients with
myelodysplastic syndromes (MDS), 11 patients were reported as
having possible disease progression, among whom 4 patients had
confirmation of acute myelogenous leukemia (AML) during
-- Nplate is not indicated for the treatment of thrombocytopenia
due to MDS or any cause of thrombocytopenia other than chronic
-- Monitor CBCs, including platelet counts and peripheral blood
smears, prior to initiation, throughout, and following
discontinuation of Nplate therapy.
-- Prior to the initiation of Nplate, examine the peripheral
blood differential to establish the baseline extent of red and
white blood cell abnormalities.
-- Obtain CBCs, including platelet counts and peripheral blood
smears, weekly during the dose adjustment phase of Nplate
therapy and then monthly following establishment of a stable
Nplate dose. Obtain CBCs, including platelet counts, weekly
for at least 2 weeks following discontinuation of Nplate.
Nplate Distribution Program
-- Nplate is available only through a restricted distribution
program called Nplate(TM) NEXUS (Network of Experts
Understanding and Supporting Nplate and Patients) Program.
Under the Nplate(TM) NEXUS Program, only prescribers and
patients registered with the program are able to prescribe,
administer, and receive Nplate. This program provides
educational materials and a mechanism for the proper use of
Nplate. To enroll in the Nplate(TM) NEXUS Program, call
-- In the placebo-controlled studies, headache was the most
commonly reported adverse drug reaction, occurring in 35
percent of patients receiving Nplate and 32 percent of
patients receiving placebo. Headaches were usually of mild or
-- Most common adverse reactions (greater than or equal to 5
percent higher patient incidence in Nplate versus placebo)
were Arthralgia (26 percent, 20 percent), Dizziness (17
percent, 0 percent), Insomnia (16 percent, 7 percent), Myalgia
(14 percent, 2 percent), Pain in Extremity (13 percent, 5
percent) , Abdominal Pain (11 percent, 0 percent), Shoulder
Pain (8 percent, 0 percent), Dyspepsia (7 percent, 0 percent),
and Paresthesia (6 percent, 0 percent).
-- As with all therapeutic proteins, patients may develop
antibodies to the therapeutic protein.
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 and effective medicines from lab, to manufacturing
plant, to patient. Amgen therapeutics have changed the practice of
medicine, helping millions of people around the world in the fight
against cancer, kidney disease, rheumatoid arthritis and other serious
illnesses. With a deep and broad pipeline of potential new medicines,
Amgen remains committed to advancing science to dramatically improve
people's lives. To learn more about our pioneering science and our
vital medicines, visit www.amgen.com.
This news release contains forward-looking statements that are
based on management's current expectations and beliefs and are subject
to a number of risks, uncertainties and assumptions that could cause
actual results to differ materially from those described. 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 (SEC)
reports filed by Amgen, including Amgen's most recent annual report on
Form 10-K and most recent periodic reports on Form 10-Q and Form 8-K.
Please refer to Amgen's most recent Forms 10-K, 10-Q and 8-K for
additional information on the uncertainties and risk factors related
to our business. Unless otherwise noted, Amgen is providing this
information as of August 22, 2008 and expressly disclaims any duty to
update information contained in this news release.
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. 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 business
may be impacted by government investigations, litigation and products
liability claims. We depend on third parties for a significant portion
of our manufacturing capacity for the supply of certain of our current
and future products and limits on supply may constrain sales of
certain of our current products and product candidate development.
In addition, sales of our products are affected by the
reimbursement policies imposed by third-party payors, including
governments, private insurance plans and managed care providers and
may be affected by regulatory, clinical and guideline developments,
domestic and international trends toward managed care and health care
cost containment as well as U.S. legislation affecting pharmaceutical
pricing and reimbursement. Government and others' regulations and
reimbursement policies may affect the development, usage and pricing
of our products. In addition, we compete with other companies with
respect to some of our marketed products as well as for the discovery
and development of new products. We believe that some of our newer
products, product candidates or new indications for existing products,
may face competition when and as they are approved and marketed. Our
products may compete against products that have lower prices,
established reimbursement, superior performance, are easier to
administer, or that are otherwise competitive with our products. In
addition, 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 and there can be no guarantee of our ability to obtain or
maintain patent protection for our products or product candidates. We
cannot guarantee that we will be able to produce commercially
successful products or maintain the commercial success of our existing
products. Our stock price may be affected by actual or perceived
market opportunity, competitive position, and success or failure of
our products or product candidates. Further, 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.
The scientific information discussed in this news release related
to our product candidates is preliminary and investigative. Such
product candidates are not approved by the U.S. Food and Drug
Administration (FDA), and no conclusions can or should be drawn
regarding the safety or effectiveness of the product candidates. Only
the FDA can determine whether the product candidates are safe and
effective for the use(s) being investigated. Further, 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 FDA 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. Only the FDA
can determine whether the products are safe and effective for these
uses. Healthcare professionals should refer to and rely upon the
FDA-approved labeling for the products, and not the information
discussed in this news release.
SOURCE: Amgen Inc.
Amgen, Thousand Oaks
Trish Hawkins, 805-447-5631 (media)
Arvind Sood, 805-447-1060 (investors)