New Phase 2 Data Suggest Treatment of Anemia with Aranesp(R) (Darbepoetin Alfa) May Provide Clinical Benefits in Heart Failure Patients
ATLANTA--(BUSINESS WIRE)--March 13, 2006--
Amgen's Phase 3 RED-HF(TM) Trial Will Evaluate the Clinical Effect
of Treating Anemia in Patients with Symptomatic Heart Failure
Amgen (Nasdaq:AMGN), the world's largest biotechnology company,
announced results from a Phase 2 study that showed that treating
anemia with Aranesp(R) (darbepoetin alfa) in patients with symptomatic
heart failure was well-tolerated, effectively raised hemoglobin and
improved patients' symptoms as measured by the Kansas City
Cardiomyopathy Questionnaire (KCCQ). The results were presented today
at the 2006 American College of Cardiology (ACC) Scientific Session.
"There is increasing evidence of a link between anemia and heart
failure, and of the potential that treating anemia in heart failure
patients may be beneficial over time," said Dirk J. van Veldhuisen,
M.D., Ph.D., FESC, FACC, Department of Cardiology/Thoracic Surgery,
University Medical Center, Groningen, Netherlands. "These data are
encouraging and support the need for a large-scale, definitive trial
to determine the effect of treating anemia in heart failure patients."
Based on the evaluation of the results of the Phase 2 program and
observational studies, Amgen has initiated the Phase 3 RED-HF(TM)
(Reduction of Events with Darbepoetin alfa in Heart Failure) Trial, a
randomized, double-blind, placebo-controlled, multicenter,
multinational trial that will evaluate the effect of treatment of
anemia with Aranesp on morbidity and mortality in patients with
symptomatic heart failure.
"Despite medical advances, heart failure and its complications are
a leading cause of death and hospitalization worldwide, and there
remains a significant unmet medical need for effective treatments for
these patients," said Willard Dere, M.D., senior vice president for
Global Development and chief medical officer at Amgen. "Amgen is
committed to investigating Aranesp's potential to help heart failure
patients who also suffer from anemia through the RED-HF Trial."
About the Phase 2 Study
This 26-week study enrolled 165 patients with symptomatic heart
failure (New York Heart Association (NYHA) II-IV; HF duration greater
than or equal to 3 months), left ventricular ejection fraction (LVEF)
less than or equal to 40 percent and hemoglobin (Hb) levels of 9.0 to
12.5 g/dL. Patients were randomized to receive Aranesp subcutaneously
every two weeks at starting doses of 0.75 mcg/kg (n=56) or 50 mcg
(fixed dose; n=54) or placebo (n=55) to achieve and maintain a target
Hb of 14.0 +/- 1.0 g/dL. The primary endpoint was the rate of Hb rise
per week during the titration period. Other endpoints included change
from baseline to month six in six-minute walk distance, Patient's
Global Assessment (PGA), Minnesota Living With Heart Failure
Questionnaire (MLHFQ), KCCQ and safety.
Investigators concluded that in patients with symptomatic heart
failure and anemia, treatment with Aranesp effectively raised Hb
levels, significantly improved KCCQ total symptom score (Aranesp 8.2
vs. placebo 1.5; p = 0.027) and had a similar adverse event profile as
previously seen in clinical trials with Aranesp. Statistically
nonsignificant improvements in PGA (Aranesp 65 percent vs. placebo 49
percent; p = 0.057), MLHFQ total score (Aranesp -10.1 vs. placebo
-7.4; p = 0.413) and 6-minute walk distance (Aranesp 34.2 m vs.
placebo 11.4 m; p = 0.074) were observed. Fixed dosing was as
effective as weight-based dosing in raising Hb levels (difference:
0.05 g/dL/wk; 95 percent CI 0.01, 0.09), and no change was observed in
NYHA class (Aranesp -0.30 vs. placebo -0.23; p = 0.473). The number of
adverse events was similar across treatment groups.
Amgen Cardiovascular Clinical Trials Program
Amgen has initiated an extensive clinical trials program to study
the effect of treating anemia or chronic kidney disease (CKD)
complications on cardiovascular outcomes in different patient
populations. In addition to the RED-HF Trial, Amgen initiated TREAT
(Trial to Reduce Cardiovascular Events with Aranesp Therapy), an
ongoing trial in diabetic patients with chronic kidney disease and
anemia not requiring dialysis and will initiate a trial that will
study the effect of treating the CKD complication, secondary
hyperparathyroidism, with Sensipar(R)/Mimpara(R) (cinacalcet HCl) in
end stage renal disease (ESRD) patients on dialysis on cardiovascular
Anemia and Heart Failure
Heart failure and its complications are a leading cause of death
and hospitalization worldwide, affecting over 23 million people
worldwide and five million people in the U.S. Heart failure alone is
the leading cause of hospitalization for people over the age of 65
years and causes almost one million hospitalizations every year.
Approximately 20 to 30 percent of people diagnosed with heart failure
also suffer from anemia, resulting in increased risk of morbidity and
mortality versus patients who suffer from heart failure without
anemia. Despite current, approved therapies to treat heart failure, a
significant unmet medical need to treat the disease and its
complications still exists.
About Aranesp(R) (darbepoetin alfa)
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 because it has a longer
half-life. Aranesp was approved by the U.S. Food and Drug
Administration (FDA) in September 2001 for the treatment of anemia
associated with chronic renal failure, also known as chronic kidney
disease (CKD), for patients on dialysis and patients not on dialysis.
In July 2002, Aranesp was approved by the FDA for the treatment of
chemotherapy-induced anemia in patients with non-myeloid malignancies.
Important Safety Information
Aranesp is indicated for the treatment of anemia in patients with
nonmyeloid malignancies where anemia is due to the effect of
concomitantly administered chemotherapy.
Aranesp is contraindicated in patients with uncontrolled
hypertension. Erythropoietic therapies may increase the risk of
thrombotic events and other serious events. The target hemoglobin (Hb)
should not exceed 12 g/dL. If the Hb increase exceeds 1.0 g/dL in any
2-week period, dose reductions are recommended. In a study with
another erythropoietic product, where the target Hb was 12 - 14 g/dL,
an increased incidence of thrombotic events, disease progression, and
mortality was seen.
Cases of pure red cell aplasia (PRCA) and of severe anemia, with
or without other cytopenias associated with neutralizing antibodies to
erythropoietin have been reported in patients treated with Aranesp.
This has been reported predominately in patients with chronic renal
failure (CRF) receiving Aranesp by subcutaneous administration. A
sudden loss of response to Aranesp, accompanied by severe anemia and
low reticulocyte count, should be evaluated. If anti-erythropoietin
antibody-associated anemia is suspected, Aranesp and other
erythropoietic proteins should be withheld. Aranesp should be
permanently discontinued in patients with antibody-mediated anemia.
Patients should not be switched to other erythropoietic proteins.
The most commonly reported side effects in clinical trials were
fatigue, edema, nausea, vomiting, diarrhea, fever, and dyspnea.
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