Amgen announces top-line results of Phase 3 Aranesp® (darbepoetin alfa) RED-HF® trial

Amgen (NASDAQ:AMGN) today announced top-line results of the Phase 3 Aranesp® (darbepoetin alfa) RED-HF® (Reduction of Events With Darbepoetin Alfa in Heart Failure) Trial. The trial was initiated in 2006, and a total of 2,278 patients with symptomatic systolic heart failure and anemia (hemoglobin levels ranging from 9.0-12.0 g/dL) were randomized to receive either treatment with Aranesp to achieve a target hemoglobin of at least 13.0 g/dL (not to exceed 14.5 g/dL), or placebo. The study did not meet its primary endpoint of reducing the composite endpoint of time to death from any cause or first hospital admission for worsening heart failure (Hazard Ratio 1.01, 95 percent CI 0.90, 1.13).

“The RED-HF Trial was designed and powered to evaluate whether the treatment of anemia could improve morbidity and mortality in systolic heart failure patients,” said Michael Severino, M.D., senior vice president of Global Development and corporate chief medical officer at Amgen. “While the study did not meet its key endpoints, we thank the patients and investigators who participated in RED-HF and helped answer this important question.”

There were no new safety findings identified in the study. The most frequently reported adverse events in the study were cardiac failure, dyspnea, diarrhea, congestive heart failure and dizziness.

These summary results will be followed by full efficacy and safety analyses, which will be shared and discussed with global regulatory agencies and submitted for presentation at an upcoming medical meeting.

Aranesp is indicated for the treatment of anemia due to chronic kidney disease in patients on dialysis and not on dialysis, and for the treatment of anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy. Aranesp has not been shown to improve quality of life, fatigue or patient well-being.

RED-HF Trial Design

The RED-HF Trial is a large, event-driven, global, randomized, double-blind, placebo-controlled, Phase 3 study designed and powered to evaluate the effect of treatment with Aranesp on mortality and heart failure hospitalization. The primary endpoint of the study was the composite of time to death from any cause or first hospital admission for worsening heart failure in patients with symptomatic left ventricular systolic dysfunction and anemia. Secondary endpoints include time to death from any cause; time to cardiovascular death or first hospital admission for worsening heart failure, whichever occurs first; change from baseline to month 6 in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score; and change from baseline in KCCQ Symptom Frequency Score.

Patients with New York Heart Association (NYHA) class II, III or IV heart failure, left ventricular ejection fraction less than or equal to 40 percent, and hemoglobin greater than or equal to 9.0 g/dL and less than or equal to 12.0 g/dL were randomized 1:1 to receive subcutaneous Aranesp or placebo. The dose of Aranesp was titrated to gradually achieve and maintain a hemoglobin concentration of at least 13.0 g/dL, not to exceed 14.5 g/dL. Investigational product was administered initially every two weeks and extended to every month when patients were stable in the hemoglobin target range. The RED-HF Trial was monitored by an independent Data Monitoring Committee, which reviewed the study data on a quarterly basis throughout the duration of the trial.

About Aranesp

Aranesp was approved by the U.S. Food and Drug Administration (FDA) in 2001 for the treatment of anemia associated with chronic renal failure (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 Aranesp for the treatment of anemia caused by concomitantly administered chemotherapy in patients with non-myeloid malignancies.

The European Commission authorized the treatment of anemia caused by concomitantly administered chemotherapy in patients with non-haematological malignancies in 2002 and extended it to include non-myeloid malignancies in patients receiving chemotherapy in 2003.

For full prescribing information outside of the U.S., including important safety information, please refer to local product labeling.

Important U.S. Aranesp Product Safety Information

Aranesp is indicated for the treatment of anemia due to chronic kidney disease in patients on dialysis and not on dialysis, and for the treatment of anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy. Aranesp has not been shown to improve quality of life, fatigue, or patient well-being. It is not indicated in patients with cancer receiving hormonal agents, biologic products, or radiotherapy, unless also receiving concomitant myelosuppressive chemotherapy; in patients with cancer receiving myelosuppressive chemotherapy when the anticipated outcome is cure or as a substitute for RBC transfusions in patients who require immediate correction of anemia.

WARNINGS: ESAs INCREASE THE RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, THROMBOSIS OF VASCULAR ACCESS AND TUMOR PROGRESSION OR RECURRENCE.

Chronic Kidney Disease:

• In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target a hemoglobin level of greater than 11 g/dL.
• No trial has identified a hemoglobin target level, Aranesp® dose, or dosing strategy that does not increase these risks.
• Use the lowest Aranesp® dose sufficient to reduce the need for red blood cell (RBC) transfusions.

Cancer:

• ESAs shortened overall survival and/or increased the risk of tumor progression or recurrence in clinical studies of patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers.
• Because of these risks, prescribers and hospitals must enroll in and comply with the ESA APPRISE Oncology Program to prescribe and/or dispense Aranesp® to patients with cancer. To enroll in the ESA APPRISE Oncology Program, visit www.esa-apprise.com or call 1-866-284-8089 for further assistance.
• To decrease these risks, as well as the risk of serious cardiovascular and thromboembolic reactions, use the lowest dose needed to avoid RBC transfusions.
• Use ESAs only for anemia from myelosuppressive chemotherapy.
• ESAs are not indicated for patients receiving myelosuppressive chemotherapy when the anticipated outcome is cure.
• Discontinue following the completion of a chemotherapy course.

For the full U.S. prescribing information, click here.