Amgen to Review Benefits, Risks of ESA Therapy in Chronic Renal Failure Patients at FDA Advisory Committee

Business Wire, Sept 11, 2007

Company Recommends Hemoglobin Target of 10-12 g/dL as Risk Management Approach

THOUSAND OAKS, Calif. -- Amgen (NASDAQ:AMGN) is presenting data today on the appropriate use of Erythropoiesis Stimulating Agents (ESAs) in Chronic Renal Failure (CRF) patients to a joint meeting of U.S. Food and Drug Administration (FDA) advisory committees.

Amgen's presentation reviews data demonstrating that ESAs are safe when used appropriately and explains the critical role ESAs play in managing the debilitating effects of anemia in CRF patients. The company's presentation recognizes the potential risks observed in recent experimental trials targeting higher-than-recommended hemoglobin levels, lays out the need for an appropriate hemoglobin target of 10-12 g/dL to guide treatment and manage risk, and highlights the importance of the ongoing Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT) to provide answers on the impact of anemia treatment in CRF patients. The company also identifies areas for future study and presents data that suggests that patient response is a stronger risk factor for poor outcomes than ESA dose.

"ESA treatment changed the lives of CRF patients by filling an unmet medical need for a very sick population of dialysis patients," said Allen R. Nissenson, M.D., professor of medicine, associate dean, and director of the Dialysis Program at the University of California, Los Angeles (UCLA). "ESA treatment reduced the need for potentially problematic blood transfusions and improved patient exercise ability, physical functions and symptoms of anemia. As we continue evaluating the appropriate use of ESA therapy, it's vital to remember the patients. It's hard to overstate how sick these patients are and how vulnerable they can be to changes in treatment."

Amgen's ESA products Aranesp([R]) (darbepoetin alfa) and EPOGEN([R]) (Epoetin alfa) have been used in more than 2.2 million CRF patients.

Target Hemoglobin Range

"Physicians tell us that to optimally treat anemia in CRF patients they need a hemoglobin target range to guide ESA dosing decisions," said Preston Klassen, M.D., executive director, Clinical Development, Amgen. "In response to recent safety signals, Amgen is proposing a conservative hemoglobin target range of 10 to 12 g/dL based on clinical trial data, dialysis population surveillance data and nearly two decades of clinical experience."

In the 1980's, double-blind, randomized, placebo-controlled registrational clinical trials targeting a hemoglobin range between 10.7-12.7 g/dL showed that use of EPOGEN virtually eliminated the need for blood transfusions in dialysis patients. Amgen will discuss with the advisory committee data from these randomized clinical trials that also shows the impact of EPOGEN on improving exercise capacity and patient-reported outcomes.

A hemoglobin target range of 10-12 g/dL was included in the product labeling for EPOGEN from 1992 to 2007. In March 2007, following the publication of clinical trial results that highlighted safety concerns when ESAs are used to target hemoglobin levels of greater than 13 g/dL, the FDA and Amgen announced the addition of a black box safety warning to all ESA labels. The concept of a hemoglobin target range was removed from ESA labeling at this time.

In response to new data the National Kidney Foundation conducted a comprehensive review of all ESA clinical trials in CRF and in August 2007 updated its clinical practice guidelines for Anemia Management to state that "the selected hemoglobin target should generally be in the range 11 to 12 g/dL."

Recent Emphasis on Poorly Responsive Patients

Recent analyses of previous clinical trials has led to a focus on a subset of CRF patients whose changing health status results in transient periods of poor responsiveness to ESA therapy. In clinical trials, worse outcomes have been reported in this subset of patients, who are often described as "hyporesponders."

Poor responders appear to have a greater underlying burden of illness resulting in greater risk of mortality. ESA responsiveness reflects underlying health status and is a better predictor of clinical risk than ESA dose alone.

"Amgen welcomes discussion with FDA on potential study designs to explore approaches to dosing that will provide optimal anemia management in this subset of very ill patients," explained Dr. Klassen.

Questions about higher doses

Some analyses have shown that higher ESA doses are associated with poor outcomes. However, Amgen noted that it is difficult to determine if higher doses cause worse outcomes, or if higher doses are observed in patients who are poor responders because of worse health status.

"Generally patients with poor ESA responsiveness and who receive the highest ESA doses have very poor health status and suffer from multiple co-morbid illnesses," said Dr. Klassen. "It would be expected that these patients would have worse clinical outcomes."

Amgen will discuss with the FDA potential study designs to further explore optimal anemia management in these patients.