Amgen Announces Top-Line Results of Trial to Reduce Cardiovascular Events With Aranesp(R) Therapy

AmgenAmgen (Nasdaq: AMGN) 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((R)) Therapy, or TREAT), treatment of anemia with Aranesp((R) )(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.

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 www.amgen.com.

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