New molecular entity: FDA approved the synthetic, pegylated erythropoiesis-stimulating agent (ESA) peginesatide (Omontys, Affymax) for the treatment of anemia due to chronic kidney disease (CKD) in adult patients on dialysis.
On March 27, 2012, FDA approved the synthetic, pegylated erythropoiesis-stimulating agent (ESA) peginesatide (Omontys, Affymax) for the treatment of anemia due to chronic kidney disease (CKD) in adult patients on dialysis. Peginesatide is the first ESA to gain FDA approval for this indication since 2001.
Efficacy. Peginesatide's efficacy was evaluated as part of 2 randomized, active-controlled, open-label, multicenter clinical trials in patients with CKD who were on dialysis. In total, these trials randomized a total of 1,608 patients with hemoglobin levels initially stabilized on epoetin 1 to 3 times weekly to receive either peginesatide administered once monthly or to continue their epoetin therapy. In both studies, peginesatide was found to be non-inferior to epoetin in maintaining hemoglobin concentrations within the pre-specified hemoglobin range of 10 to 12 g/dL. Additionally, the proportion of patients receiving transfusions was similar between treatment groups in both studies. No difference in cardiovascular event rates were observed with peginesatide compared to epoetin in a pooled analysis of these clinical trials (HR=0.95; 95% CI, 0.77–1.17).
Safety. The most common side effects observed in ≥10% of dialysis patients treated with peginesatide during clinical trials included diarrhea, vomiting, hypertension, and joint, back, leg, or arm pain. Myocardial infarction, stroke, and thromboembolism are known serious adverse effects of ESAs, and targeting hemoglobin levels >11 g/dL when using ESAs is known to increase patients' risk of these cardiovascular adverse events. Consequently, the lowest dose of peginesatide sufficient to reduce the need for red blood cell (RBC) transfusions should always be used. Peginesatide is not indicated or recommended for the treatment of anemia in patients with CKD who are not on dialysis because trials demonstrated a higher risk of cardiovascular adverse events when compared to darbepoetin (HR=1.32; 95% CI, 0.97–1.81). Peginesatide and other ESAs should not be used in patients receiving treatment for cancer as they may cause tumor progression or recurrence. Peginesatide is contraindicated in uncontrolled hypertension.