Peginesatide in Patients Undergoing Hemodialysis

Posted by Sara Fazio • January 25th, 2013

In two new randomized, controlled studies involving patients undergoing long-term hemodialysis, peginesatide, a synthetic peptide-based erythropoiesis-stimulating agent, was compared with epoetin for the treatment of anemia. The two agents were similarly effective.  Read both the EMERALD study and the PEARL study here.

Partial correction of anemia with erythropoiesis-stimulating agents (ESAs) is a cornerstone of therapy for patients undergoing hemodialysis, because these agents increase hemoglobin levels, which results in a reduction in blood-transfusion rates. Partial correction of anemia has also been reported to enhance quality of life.

Clinical Pearls

What is the mechanism of action of peginesatide, and how does it differ from other agents in this class?

Peginesatide is a synthetic, pegylated, peptide-based ESA that was approved by the Food and Drug Administration in March 2012 for the treatment of anemia due to chronic kidney disease in adults undergoing hemodialysis. Peginesatide has no sequence homology to, or immunologic cross-reactivity with, erythropoietin. It stimulates the erythropoietin receptor in vivo, thereby acting as an “epomimetic” agent. Previous studies have suggested that peginesatide may be effective in raising and maintaining hemoglobin levels. Peginesatide is administered monthly. Until recently, the ESAs that were available were erythropoietin analogues manufactured with the use of recombinant DNA technology. Most patients undergoing hemodialysis receive epoetin alfa up to three times a week, whereas fewer patients receive darbepoetin alfa once a week or every 2 weeks.

• What were the primary results of this study comparing peginesatide to epoetin in patients with anemia undergoing hemodialysis?

The authors studied the efficacy of peginesatide as compared with other ESAs, using the target hemoglobin level (10 to 12 g per  deciliter in the EMERALD studies) that was the standard when the trials were conducted. Among patients undergoing hemodialysis (those in the EMERALD 1 and EMERALD 2 studies), peginesatide administered once a month was as effective as epoetin administered one to three times a week in maintaining hemoglobin levels.

Figure 2. Mean Hemoglobin Level, According to Study Week.

Morning Report Questions

Q: What were secondary end points in this study?

A: The proportion of patients who received at least one transfusion during the dose-adjustment and evaluation periods was similar in the two treatment groups: 10.3% in the peginesatide group and 8.6% in the epoetin group in the EMERALD 1 study (relative risk with peginesatide, 1.21; 95% CI, 0.76 to 1.92) and 7.7% and 9.9% in the two groups, respectively, in the EMERALD 2 study (relative risk, 0.79; 95% CI, 0.50 to 1.24). The proportion of patients in whom the mean hemoglobin concentration was maintained within the target range during the evaluation period was also similar in the two groups: 63.0% and 71.7%, respectively, in the EMERALD 1 study (relative response rate with peginesatide, 0.88; 95% CI, 0.79 to 0.97) and 63.5% and 65.9% in the EMERALD 2 study (relative response rate with peginesatide, 0.96; 95% CI, 0.87 to 1.07). In both studies, the iron status at the end of the evaluation period and the percentage of patients receiving iron supplementation during the study were generally similar in the two groups.

Q: Did adverse events differ between the two groups studied?

A: Adverse (including serious adverse) events in the EMERALD studies were similar in the peginesatide and epoetin groups and were consistent with expected adverse events in patients undergoing hemodialysis. No between-group differences were observed in the rate of events associated with the erythropoiesis-stimulating class of drugs, including venous thromboembolic events, complications related to hemodialysis access, hypertension-related events, and cancer. Peginesatide-specific neutralizing antibodies developed in 12 patients; antierythropoietin antibodies did not develop in any patients, and no pure red-cell aplasia cases were reported. Longer-term follow-up of patients is warranted to determine the immunogenicity profile of peginesatide, including the incidence of antibody formation and potential clinical consequences.

Table 2. Component Events of the Composite Safety End Point, Most Common Serious Adverse Events, and Adverse Events Associated with the Erythropoiesis-Stimulating Agent (ESA) Class of Drugs. 

 

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