Amgen (NASDAQ:AMGN) today announced the analysis of the Aranesp(R)
(darbepoetin alfa) Danish Head and Neck Cancer (DAHANCA) 10 study
presented by investigators from the DAHANCA study group in the
Presidential Session at the 14th European Cancer Conference (ECCO) in
Barcelona, Spain. As previously communicated, the trial was stopped on
Nov. 28, 2006, due to futility following an interim analysis, which
showed low likelihood that the Aranesp arm would demonstrate improved
outcomes.
This independent, investigator-sponsored study is a component of
Amgen's ongoing Aranesp pharmacovigilance program and was designed to
evaluate the experimental circumstance of whether using Aranesp to
maintain hemoglobin (Hb) levels between 14.0 to 15.5 g/dL results in
better outcomes for patients with squamous cell carcinoma of the head
and neck (HNSCC) by allowing more oxygen to reach the tumor, making it
more sensitive to radiotherapy. Aranesp is not indicated for
concomitant treatment with radiotherapy alone and the Hb targets in
this study exceeded the current approved labeling in both Europe and
the U.S.
The study investigators completed their analysis of the data in
July 2007 and have concluded that patients with primary HNSCC who were
treated with Aranesp had significantly poorer tumor control after
radiotherapy. Of 515 patients eligible for analysis, the results
demonstrated a poorer outcome with Aranesp treatment in 5-year
loco-regional control (56 percent with Aranesp versus 69 percent for
the control group; RR: 1.44 (1.06-1.96), p=0.02), the primary endpoint
for the study.
There were no significant differences in overall survival (RR:
1.28 (0.98-1.68), p=0.08), the risk of developing distant metastases
or in non-cancer related deaths. There was also no enhanced risk of
cardiovascular events observed in the Aranesp arm. Systematic imaging
was not applied in this study. Instead, the study relied on clinical
methodology for detection of disease persistence or recurrence. This
method is not the U.S. or European regulatory standard for assessing
disease progression in HNSCC.
The study was conducted by the independent DAHANCA study group,
and thus Amgen did not have control over the study conduct or data
analysis. Amgen has not had the opportunity to validate the assessment
of the raw data. In early December 2006, Amgen shared with regulatory
agencies, including the European Agency for the Evaluation of
Medicinal Products (EMEA) and the U.S. Food and Drug Administration
(FDA), the preliminary interim data report that was posted on the
DAHANCA study group's Web site.
The boxed warning section of the U.S. labeling for
erythropoiesis-stimulating agents (ESAs) was updated in March 2007 to
include information about the DAHANCA 10 preliminary results.
"Aranesp is approved to treat anemic patients receiving
chemotherapy, and is not approved for use by the FDA or EMEA for the
experimental indication investigated in this trial," said Willard
Dere, M.D., Amgen senior vice president and international chief
medical officer. "Amgen continues to recommend the use of Aranesp to
treat patients with anemia only in accordance with its approved
product labeling, and remains committed to providing patients and
their physicians with the most accurate information to make informed
treatment decisions."
About Aranesp
Aranesp is a recombinant erythropoietic protein (a protein that
stimulates production of red blood cells, which carry oxygen). Amgen
revolutionized the treatment of anemia 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 molecule and remains in the
bloodstream longer than epoetin alfa as demonstrated by its longer
half-life.
Aranesp was granted marketing authorization by the European
Commission in 2001 for the treatment of anemia associated with chronic
renal failure (CRF), also known as chronic kidney disease (CKD), in
adults and pediatric 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 anemia 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 anemia associated with CRF, in all European
pediatric 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 thromboembolic 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.
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