Amgen (Nasdaq: AMGN) today announced the publication of results from TREAT (the Trial to Reduce Cardiovascular Events with Aranesp® Therapy), a large, randomized, double-blind, placebo-controlled, Phase 3 pivotal study of patients with chronic kidney disease (CKD) not on dialysis, moderate anemia and type-2 diabetes. The study, published online today in the New England Journal of Medicine and presented at the annual meeting of the American Society of Nephrology (ASN), failed to meet its primary objectives of demonstrating a reduction in all-cause mortality, cardiovascular morbidity, including heart failure, heart attack, stroke, or hospitalization for myocardial ischemia, or end-stage renal disease (ESRD).
The primary endpoints of the study 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 ESRD. Among the components of the primary cardiovascular composite endpoint, the risk of stroke increased by almost two-fold in patients in the Aranesp arm (101 patients [5.0 percent] vs. 53 patients [2.6 percent]; hazard ratio, 1.92; 95 percent confidence interval, 1.38 to 2.68; P<0.001). Although stroke is a recognized risk with erythropoiesis-stimulating agent (ESA) therapy, and has been identified in warnings in United States (U.S.) labeling since 2001, the risk observed in TREAT is of higher magnitude than that seen in previous clinical trials in CKD patients not on dialysis.
A post hoc analysis indicates that there were no significant differences between treatment arms in the incidence of cancer or of all-cause deaths in patients who developed cancer during the trial. However, this analysis also showed an excess in overall mortality among patients in the Aranesp arm with a history of cancer. This finding requires further investigation.
"ESAs were originally approved to raise red blood cell levels and to reduce the need for transfusions. In the TREAT study, we sought to demonstrate that, beyond these benefits, ESA therapy reduces cardiovascular morbidity and mortality. This hypothesis is not supported by the data," said Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen. "As the first, large-scale placebo-controlled study to examine the use of anemia therapy in diabetic CKD patients not on dialysis, the TREAT results demonstrated that in many diabetic CKD patients not on dialysis with moderate anemia, the risk of treatment to a target hemoglobin level of 13 g/dL will exceed the benefit of reducing the need for transfusions."
Amgen has shared this information with global regulatory authorities and anticipates that the TREAT results will be included in labeling once discussions are complete.
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