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Aranesp Combined Patient Level Analyses Provide
Additional Evidence of Efficacy and Safety
Amgen (NASDAQ:AMGN) today
announced data from a Phase 2, randomized,
multicenter, open-label study that suggest
extended dosing of Aranesp(R) (darbepoetin alfa)
paired with chemotherapy treatment (every two or
every three weeks depending on chemotherapy
regimen) appeared to be efficacious with respect
to changes in hemoglobin (Hb), with no
unexpected adverse events observed when compared
to weekly dosing.
Additionally, results from two combined patient
level analyses suggest that patients treated
with Aranesp experienced a decrease in blood
transfusions and improvement in hematologic
response. These analyses do not suggest a
negative impact on overall survival or
progression-free survival between patients
receiving chemotherapy treatment with Aranesp
and those that did not receive Aranesp
treatment. These data were presented at the 14th
European Cancer Conference (ECCO) in Barcelona, Spain
(Abstract # 1.141, 1.120, 1.104).
About the Phase 2 Study
This Phase 2 study is the first prospective
trial illustrating how various Aranesp dosing
regimens can be paired with chemotherapy
administered across a range of dosing schedules.
"Flexibility in dosing is important for
physicians to optimize anemia management and
meet patient needs," said Timothy Rearden, M.D.,
Hematology Oncology Consultant, Inc. "In this
study, Aranesp was consistently effective
regardless of dosing frequency, providing
healthcare professionals with the ability to
adapt Aranesp treatment as required."
The mean change in Hb from baseline to week 13
was comparable between extended dosing (every
two or every three weeks depending on
chemotherapy regimen) and weekly dosing. The
percentage of patients who achieved a Hb greater
than or equal to 11 g/dL by Kaplan-Meier
estimates was also similar (76 percent for
weekly dosing and 71 percent for extended
dosing).
The trial was a Phase 2, 25-week open-label
study to evaluate non-inferiority of Aranesp in
patients with anemia as a result of chemotherapy
treatment who were randomized 1:1 to either an
extended dosing schedule (n=378) or a weekly
schedule (n=374).
Patients in the arm receiving an extended dose
schedule of Aranesp received 300 mcg Q2W if
chemotherapy treatment (CTX) was QW, Q2W, or Q4W
or 500 mcg Q3W if CTX was Q3W. Patients in the
arm receiving a weekly schedule of Aranesp
(DA-QW) received 150 mcg QW regardless of CTX
schedule. The QW and Q2W fixed dosing schedules
utilized in this study are not approved dosing
options. Q3W 500 mcg fixed dosing is the
recommended initial dose with alternate weight
based dosing options available at QW and Q3W.
Stratification factors were chemotherapy cycle
length, screening Hb (less than 10 g/dL versus
greater than or equal to 10 g/dL) and type of
cancer (lung/gynecological versus other
cancers). The primary endpoint was change in Hb
from baseline to week 13. Demographics between
the two groups were broadly similar.
Aranesp Combined Patient Level Analyses
Results
Two combined analyses reported patient level
data from six Amgen-sponsored,
placebo-controlled, randomized trials of Aranesp
to treat anemia as a result of chemotherapy in
patients with screening Hb less than or equal to
11 - 13 g/dL, nonmyeloid malignancies, greater
than or equal to one prior chemotherapy cycle,
and additional planned chemotherapy cycles.
Amgen presented the results of these combined
patient level analyses at the U.S. Food and Drug
Administration's Oncologic Drugs Advisory Committee meeting in May
2007.
While preserving initial randomization, patient
level data from 2,112 patients was analyzed to
determine differences between Aranesp (n=1,200)
treatment and placebo (n=912). The results
suggest that patients treated with Aranesp
experienced a decrease in blood transfusions,
improvement in hematologic response, and an
expected increased risk of thromboembolic events
(TE). No differences in risks of death, disease
progression or progression-free survival were
observed between the two groups.
"The results of these combined patient level
analyses further add to the large scientific
body of evidence that ESAs are safe and
effective when used according to their approved
label. The increased risk of TEs has long been
observed and appropriately represented for in
class labeling for ESAs," said Heinz Ludwig,
M.D., Center for Oncology and Haematology,
Wilhelminen
Hospital, Vienna, Austria.
The Aranesp group had an approximate 54 percent
relative risk reduction for transfusions (HR:
0.46, 95 percent CI: 0.39, 0.55) and also were
approximately more than twice as likely to
achieve a hematopoietic response (HR: 2.40, 95
percent CI: 2.10, 2.75). The relative risk for
TEs was approximately 50 percent higher in the
Aranesp group (HR: 1.57, 95 percent CI: 1.10,
2.26). The rates of TEs were eight percent in
patients treated with Aranesp and five percent
in placebo patients. These rates are similar to
what has been reported in current product
labeling.
A second combined analysis evaluated the
association between achieved Hb levels or rates
of Hb increase and safety outcomes in anemic
cancer patients undergoing chemotherapy. The
analysis included 1,200 patients treated with
Aranesp. Achieving a Hb greater than 12 or 13 g/dL
or a Hb increase of greater than 1 g/dL in 14
days or greater than 2 g in 28 days did not
appear to be associated with an increased risk
of death or disease progression. Risk of TEs was
not clearly related to achieving Hb of greater
than 12 or greater than 13, although rates of
rise greater than 1g in 14 days and greater than
2 g in 28 days were associated with a trend
towards increased risk. These risks of TEs are
consistent with those already noted in ESA
product labels.
A similar pattern was seen when deaths were
identified during a study's
follow-up period. No increased risk of disease
progression and progression-free survival was
seen in patients who achieved a Hb greater than
12 g/dL, Hb greater than 13 g/dL, a Hb increase
of greater than 1 g/dL in 14 days or greater
than 2 g in 28 days. It should be recognized
that in this combined analysis, the patients
ability to respond is an important potential
confounder.
The results of the combined analyses presented
at ECCO appear to suggest that patients
receiving chemotherapy who are able to reach a
Hb level of above 12 g/dL do not experience an
increased risk of on-study death and disease
progression. A higher rate of TEs was associated
with increased rates of Hb increase, which is a
recognized risk in this patient population
treated with ESAs. These data provide further
information regarding the relationship of
achieved Hb and safety outcomes for Aranesp.
About Aranesp
Aranesp is a recombinant erythropoiesis-stimulating
protein (a protein that stimulates production of
red blood cells, which carry oxygen). Amgen
revolutionised the treatment of anaemia with the
development of recombinant erythropoietin,
Epoetin alfa. Building on this heritage, Amgen
developed Aranesp, a unique erythropoiesis
stimulating protein, which contains two
additional sialic acid-containing carbohydrate
chains compared to the epoetin alfa and epoetin
beta molecule and remains in the bloodstream
longer than epoetin alfa and epoetin beta as
demonstrated by its longer half-life.
Aranesp was granted marketing authorisation by
the European Commission in 2001 for the
treatment of anaemia associated with chronic
renal failure (CRF), also known as chronic
kidney disease (CKD), in adults and paediatric
subjects 11 years of age or older. In 2002, the
European Commission approved Aranesp for the
treatment of anemia in adult cancer patients
receiving chemotherapy with solid tumors. This
patient population was subsequently expanded in
2003 to include treatment of symptomatic anaemia
in adult cancer patients with non-myeloid
malignancies receiving chemotherapy. Approval
was granted in 2004 for extended dosing
intervals of once-every-three-weeks in the
treatment of anemia in adult cancer patients
with non-myeloid malignancies who are receiving
chemotherapy and up to once-per-month Aranesp
administration in the treatment of anemia in CKD
patients not on dialysis. In 2006, the Aranesp
label was updated to allow CKD patients on
dialysis to switch from rHuEPO one to three
times a week to Aranesp every two weeks. In
2007, the Aranesp label was updated to allow for
treatment of anaemia associated with CRF, in all
European paediatric patients on dialysis or not
on dialysis.
Aranesp was approved by the U.S. Food and Drug
Administration (FDA) in September 2001 for the
treatment of anemia associated with 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.
Important EU Aranesp Safety Information
Aranesp is contraindicated in patients with
uncontrolled hypertension. Erythropoietic
therapies may increase the risk of thrombotic
and other serious events; regional guidelines
should be referred to for target and maximum
hemoglobin levels, and dose adjustment rules
should be performed in line with regional
prescribing information.
The most commonly reported side effects in
clinical trials were arthralgia, edema,
injection site pain and thromembolic event
reactions. Prescribers are recommended to
consult regional prescribing information before
prescribing Aranesp, including side-effects,
precautions and contra-indications.
Important U.S. Aranesp
Safety Information
Use the lowest dose of Aranesp(R) that will
gradually increase the hemoglobin concentration
to the lowest level sufficient to avoid the need
for red blood cell transfusion.
Aranesp(R) and other erythropoiesis-stimulating
agents (ESAs) increased the risk for death and
for serious cardiovascular events when
administered to target a hemoglobin of greater
than 12 g/dL
Cancer
Patients: Use of ESAs
-
Shortened
the time to tumor progression in patients
with advanced head and neck cancer receiving
radiation therapy when administered to
target a hemoglobin of greater than 12 g/dL,
-
Shortened overall survival and increased
deaths attributed to disease progression at
4 months in patients with metastatic breast
cancer receiving chemotherapy when
administered to target a hemoglobin of
greater than 12 g/dL,
-
Increased the risk of death when
administered to target a hemoglobin of 12 g/dL
in patients with active malignant disease
receiving neither chemotherapy or radiation
therapy. ESAs are not indicated for this
population.
Patients receiving ESAs pre-operatively for
reduction of allogeneic red blood cell
transfusions: A higher incidence of deep venous
thrombosis was documented in patients receiving
Epoetin alfa who were not receiving prophylactic
anticoagulation. Aranesp(R) is not approved for
this indication.
Aranesp is contraindicated in patients with
uncontrolled hypertension.
About Amgen
Amgen discovers, develops 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.
Forward-Looking Statements
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news release contains forward-looking statements
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CONTACT: Amgen
Sabeena Ahmad, +41 41 3692 530 (EU media,
oncology)
Ashleigh Koss, 805-313-6151 (US media, oncology)
Arvind Sood, 805-447-1060 (investors)
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