ESAs Provide Important Clinical Benefits to Cancer Patients With
Anemia Due to Chemotherapy; Ongoing and Planned Risk Management Will
Further Reduce Risks
THOUSAND OAKS, Calif.--(BUSINESS WIRE)--March 13, 2008--Amgen Inc.
(NASDAQ: AMGN) will today present the benefits and risks of
Erythropoiesis-stimulating Agents (ESAs) in cancer patients with
anemia due to concomitantly administered chemotherapy at a meeting
with the U.S. Food and Drug Administration´s (FDA) Oncologic Drugs
Advisory Committee (ODAC). ESAs provide these patients with the only
therapeutic alternative to red blood cell (RBC) transfusions, which
have known and uncertain risks.
"ESAs provide an unequivocal treatment benefit for cancer patients
undergoing chemotherapy by reducing the need for blood transfusions,"
said Roger M. Perlmutter, M.D., Ph.D., executive vice president, of
Research and Development at Amgen. "We look forward to discussing with
the ODAC a robust risk management program to reduce ESA risks while
still providing access and benefits to the appropriate patients."
For a complete review and analysis of Amgen´s presentation to the
ODAC, Amgen´s and FDA´s briefing materials for the ODAC meeting are
available at www.Amgen.com or www.fda.gov.
Highlights of Amgen´s presentation to the ODAC will include the
ESA Treatment Benefits
ESAs provide the only therapeutic alternative to RBC
transfusions in cancer patients with anemia due to
concomitantly administered chemotherapy.
In well-controlled clinical trials, ESAs have been proven to
reduce RBC transfusions in patients with anemia receiving
If ESAs were not available, data from Amgen´s
placebo-controlled clinical trials suggest that twice as many
patients receiving chemotherapy would require RBC
Risks of ESAs
Eight ESA studies have shown safety signals when patients were
studied at higher than currently labeled hemoglobin targets
and/or for new experimental indications (such as radiotherapy
or patients not receiving chemotherapy).
Six of these eight studies were discussed at ODAC meetings in
2004 and 2007. Since the May 2007 ODAC meeting, new data from
two studies have become available, including interim results
from the PREPARE (a study in neo-adjuvant breast cancer) and
long-term follow up data from GOG-191 (a study in cervical
cancer), both of which targeted hemoglobin levels higher than
in the current approved product label.
These safety signals are inconsistently observed across a
total of 59 studies.
The current label notes the hypothetical risks of shortened
overall survival and/or tumor progression when hemoglobin
targets are less than or equal to 12 g/dL.
Potential mechanisms for these safety signals may include
thromboembolic events which have long been recognized in ESA
labeling. Other mechanisms include the recently labeled but
unproven hypothesis of tumor progression and reduced efficacy
of radiotherapy at high hemoglobin levels.
Amgen will review the totality of clinical evidence with ODAC,
including all favorable and unfavorable studies.
"Although these safety signals have been inconsistently observed
across a number of ESA studies, Amgen nonetheless takes them very
seriously, and is committed to conducting a controlled clinical trial
based on the current label to definitively address these issues," said
Perlmutter. "Patient safety is our top priority. To this end, we look
forward to the ODAC´s recommendations on the proposed clinical study
and will continue to collaborate with the FDA, NCI and others to
address these safety concerns."
Risks of Blood Transfusions
The use of blood transfusions to treat anemia carries several
types of known and uncertain risks for patients with cancer and for
the public as a whole. Additionally, the benefits of RBC transfusions
are transient, requiring some patients to receive multiple
transfusions during the duration of their chemotherapy treatment.
Although the blood supply is currently considered safer than
in the past, there are both known and unknown risks associated
Blood transfusions also can be associated with transfusion
reactions or other antibody mediated problems.
Physicians have stated that transfusions are disruptive for
patients, caregivers and physicians and divert substantial
resources that would otherwise be available for patient care.
Proposed Risk Management Program to Preserve Access and Minimize
Additional risk management, through additional product labeling
updates and a formal education and communication program, will
minimize risk while the necessary data are acquired from clinical
trials designed to address the unanswered safety questions. Amgen will
propose to the ODAC a risk program that is designed to minimize the
risks of ESA therapy, discourage off-label use, and promote educated
benefit-risk decisions for each patient.
Aranesp(R) (darbepoetin alfa) was approved by the FDA in September
2001 for the treatment of anemia associated with chronic renal failure
(CRF), for patients on dialysis and patients not on dialysis. In July
2002, the FDA approved weekly dosing of Aranesp for the treatment of
anemia caused by concomitantly administered chemotherapy in patients
with nonmyeloid malignancies and in March 2006, the FDA approved
every-three-week dosing in these patients.
Amgen launched EPOGEN(R) (Epoetin alfa), one of the first
biologically derived human therapeutics, into the U.S. medical
marketplace in 1989 for the treatment of anemia in patients with
chronic renal failure on dialysis. EPOGEN is a recombinant protein
with the same mechanism of action as endogenous human erythropoietin,
a protein produced by the kidneys to stimulate the production of
oxygen-transporting red blood cells.
Important Aranesp and EPOGEN Safety Information
WARNINGS: INCREASED MORTALITY, SERIOUS CARDIOVASCULAR and
THROMBOEMBOLIC EVENTS, and TUMOR PROGRESSION.
Renal failure: Patients experienced greater risks for death and
serious cardiovascular events when administered erythropoiesis-
stimulating agents (ESAs) to target higher versus lower hemoglobin
levels (13.5 vs. 11.3 g/dL; 14 vs. 10 g/dL) in two clinical studies.
Individualize dosing to achieve and maintain hemoglobin levels within
the range of 10 to 12 g/dL.
ESAs shortened overall survival and/or time-to-tumor progression in
clinical studies in patients with breast, non-small cell lung, head
and neck, lymphoid, and cervical cancers when dosed to target a
hemoglobin of greater than or equal to 12 g/dL.
The risks of shortened survival and tumor progression have not been
excluded when ESAs are dosed to target a hemoglobin of less than 12
To minimize these risks, as well as the risk of serious cardio- and
thrombovascular events, use the lowest dose needed to avoid red blood
Use only for treatment of anemia due to concomitant
Discontinue following the completion of a chemotherapy course.
Perisurgery: EPOGEN(R) increased the rate of deep venous thromboses in
patients not receiving prophylactic anticoagulation. Consider deep
venous thrombosis prophylaxis.
Aranesp and EPOGEN are contraindicated in patients with
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