Amgen Announces Top-Line Results of Trial to Reduce Cardiovascular Events With Aranesp(R) Therapy (TREAT) in CKD Patients With T
26 August 2009 - 6:12AM
PR Newswire (US)
No Statistically Significant Difference in Cardiovascular and Renal
Composite Endpoints Between Aranesp and Placebo THOUSAND OAKS,
Calif., Aug. 25 /PRNewswire-FirstCall/ -- Amgen (NASDAQ: AMGN)
today announced that in a large, randomized, double-blind,
placebo-controlled, Phase 3 study of patients with chronic kidney
disease (CKD) (not requiring dialysis), anemia and type-2 diabetes
(the Trial to Reduce Cardiovascular Endpoints with Aranesp Therapy,
or TREAT), treatment of anemia with Aranesp (darbepoetin alfa) to a
hemoglobin target of 13 g/dL had no statistically significant
effect on either of two primary endpoints compared with placebo
treatment. The two primary endpoints were a composite of time to
all-cause mortality or cardiovascular morbidity (including heart
failure, heart attack, stroke, or hospitalization for myocardial
ischemia) and a composite of time to all-cause mortality or chronic
renal replacement therapy. Among the elements that formed these
composite endpoints, an excess of stroke events (a labeled risk of
Aranesp therapy) occurred in the Aranesp-treated patients compared
to those receiving placebo. These summary results will be followed
by full efficacy and safety analyses, which will be shared with
global regulatory authorities and presented at an upcoming medical
meeting later this year. "TREAT was designed to answer important
questions about the effects of erythropoiesis-stimulating agents
(ESAs) on cardiovascular and renal outcomes in patients with renal
insufficiency and type-2 diabetes. It is by any measure the most
comprehensive analysis that has ever been performed to examine the
impact of anemia therapy in patients who do not yet require
dialysis. The trial will provide nephrologists with important
information as they endeavor to improve renal care," said Roger M.
Perlmutter, M.D., Ph.D., executive vice president of Research and
Development at Amgen. "In contrast to a recent, smaller study of
ESAs in a similar patient population, TREAT did not show a
statistically significant adverse effect on all-cause mortality or
cardiovascular morbidity when patients were treated to a hemoglobin
target of 13 g/dL. We continue to believe that ESAs have a
favorable benefit:risk profile when used according to the approved
label." Currently, Aranesp is indicated for the treatment of anemia
in patients with chronic renal failure (CRF), including patients on
dialysis and patients not on dialysis. The approved label for
Aranesp recommends individualizing dosing to achieve and maintain
hemoglobin levels within the range of 10 to 12 g/dL. TREAT studied
uses for Aranesp in which it is not approved. TREAT Study Design
TREAT was an international, Phase 3, randomized, double-blind,
placebo-controlled study of 4,038 chronic kidney disease (CKD)
patients with type-2 diabetes and anemia. It is the largest study
of ESA use in CKD patients to date. Patients enrolled in the study
were randomized in a one-to-one ratio to receive either treatment
with Aranesp to a target hemoglobin of 13 g/dL or placebo. Due to
the increased risk of negative outcomes associated with low
hemoglobin levels, patients in the control arm whose hemoglobin
fell below 9 g/dL were given Aranesp until their hemoglobin level
was 9 g/dL. Investigators were blinded to this intervention. TREAT
had two primary endpoints. The first evaluated time to all-cause
mortality or cardiovascular morbidity including heart attack
(myocardial infarction), congestive heart failure, hospitalization
for angina (myocardial ischemia), or stroke (cerebrovascular
accident). The second primary endpoint evaluated time to all-cause
mortality or chronic dialysis. TREAT was not designed to determine
the appropriate hemoglobin target in this patient population. For
patients randomized to the Aranesp group, the starting dose was
0.75 mcg/kg administered subcutaneously every two weeks; subsequent
doses were titrated to achieve hemoglobin target of 13.0 g/dL. Once
the target hemoglobin was reached, the frequency of administration
was extended to once-monthly. Chronic Kidney Disease: Impact and
Prevalence CKD affects more than 26 million Americans and millions
more worldwide. The disease is characterized by progressive kidney
damage and impaired kidney function and is most often caused by
type-2 diabetes or high blood pressure. When CKD progresses to
kidney failure, chronic dialysis or a kidney transplant are
required to sustain life. Approximately 350,000 people in the
United States are on dialysis today. Anemia is a common
complication of CKD that may begin in the early stages of the
disease and becomes more common and severe as kidney function
declines. Studies have shown that anemia is associated with an
increased risk of mortality and cardiovascular morbidity in CKD
patients. About Aranesp Aranesp was approved by the U.S. Food and
Drug Administration in 2001 for the treatment of anemia associated
with CRF for patients on dialysis and patients not on dialysis. The
European Commission granted marketing authorization for the same
indication in 2001 and subsequently updated it for CRF patients
with symptomatic anemia in 2008. In 2002, the FDA approved the
treatment of anemia caused by concomitantly administered
chemotherapy in patients with nonmyeloid malignancies. The European
Commission authorized the treatment of anemia caused by
concomitantly administered chemotherapy in patients with
non-haemological malignancies in 2002 and extended it to include
non-myeloid malignancies in patients receiving chemotherapy in
2003. Important Aranesp 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. Cancer: --
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. -- To minimize
these risks, as well as the risk of serious cardio- and
thrombovascular events, use the lowest dose needed to avoid red
blood cell transfusions. -- Use only for treatment of anemia due to
concomitant myelosuppressive chemotherapy. -- ESAs are not
indicated for patients receiving myelosuppressive therapy when the
anticipated outcome is cure. (This information is specific to the
U.S. prescribing information) -- Discontinue following the
completion of a chemotherapy course. Aranesp is contraindicated in
patients with uncontrolled hypertension. All patients, including
patients with cancer or chronic kidney failure: -- You may get
serious heart problems such as heart attack, stroke, heart failure,
and may die sooner if you are treated with Aranesp to a hemoglobin
level above 12 g/dL. -- You may get blood clots at any time while
taking Aranesp. If you are receiving Aranesp and you are going to
have surgery, talk to your healthcare provider about whether or not
you need to take a blood thinner to lessen the chance of blood
clots during or following surgery. Clots can form in blood vessels
(veins), especially in your leg (deep venous thrombosis or DVT).
Pieces of a blood clot may travel to the lungs and block the blood
circulation in the lungs (pulmonary embolus). About Amgen 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
http://www.amgen.com/. Forward-Looking Statements This news release
contains forward-looking statements that are based on management's
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Hurley: 805-447-7845 (media) Arvind Sood: 805-447-1060 (investors)
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