Pharmacology Update: Peginesatide Injection (Omontys®)
Pharmacology Update
Peginesatide Injection (Omontys®)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Elliott and Chan report no financial relationships relevant to this field of study.
A completely synthetic, once-monthly, erythropoiesis-stimulating agent has been approved for the treatment of anemia in dialysis patients. Peginesatide is a pegylated dimeric peptide that does not share any sequence homology to the endogenous human erythropoietin but shares a similar mechanism of stimulating erythropoiesis.1 It marketed by Affymax, Inc. and Takeda Pharmaceuticals U.S.A. as Omontys.
Indications
Peginesatide is indicated for the treatment of anemia due to chronic kidney disease (CKD) in adult patients on dialysis.2
Dosage
The initial recommended dose is 0.04 mg/kg body weight given once monthly. The dose may be given as a single intravenous or subcutaneous injection. The subcutaneous and intravenous routes of administration appear similar in effectiveness.3 For patients already taking epoetin, peginesatide should be started 1 week after the last dose of epoetin. For those on darbepoetin, peginesatide can be started at the next schedule.
Peginesatide is available as 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, and 6 mg single-dose preservative-free vials/syringes and as 10 mg/mL multiple use vials with preservative.
Potential Advantages
Peginesatides is administered once monthly, compared to weekly or every other week with epoetin alfa or darbepoetin alfa. There is no apparent cross reactivity between antierythropoietin antibodies and peginesatides.4 The drug has been reported to be effective in red-cell aplasia caused by antierythropoietin antibodies.
Potential Disadvantages
An increase in composite cardiovascular safety endpoints (all-cause mortality, myocardial infarction, stroke, or serious cardiovascular adverse events of congestive heart failure, unstable angina, or arrhythmia) compared to darbepoetin has been reported in non-dialysis CKD patients.2,5 A small percentage of patients develop peginesatides-specific binding antibodies (1.2%).2 The incidence was higher when the drug was given subcutaneously (1.9%) compared to intravenous administration (0.7%). Peginesatide shares the class warning for erythropoiesis-stimulating agents, namely increased risk of death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access, and tumor progression or recurrence.1
Comments
Peginesatide was studied in four Phase 3 studies. Two studies (PEARL 1 and PEARL 2) compared the efficacy and safety to darbepoietin in patients with CKD not on dialysis. Two studies (EMERALD 1 and EMERALD 2) compared the efficacy and safety with epoetin alfa in patients on dialysis. Subgroup analysis of non-dialysis patients in the PEARL trials showed significant increased risk of composite cardiovascular events and all-cause mortality in the peginesatide group.5 The upper limit of the 90% confidence interval (CI) of the hazard ratio was 1.73, exceeding the acceptable limit of 1.3. Analysis of the EMERALD data (1066 peginesatide, 542 epoetin) showed similar rates of cardiovascular events and mortality.6 The upper limit of the 90% CI was 1.13. The FDA approval for use in dialysis patients was based on these data. Peginesatide met the criteria for noninferiority in maintaining hemoglobin levels compared to epoetin assessed at week 29-36 of treatment.2 Peginesatide has not been shown to improve symptoms of anemia or quality of life.
Clinical Implications
Peginesatide is the first synthetic erythropoiesis-stimulating drug approved. Its only advantage appears to be the convenience of once-monthly dosing. However, this advantage may not be truly significant in patients who require dialysis three times a week. Evidence suggests an increased cardiovascular/mortality risk in nondialysis patients, which raises concern for long-term safety of peginesatide.
References
1. Green JM, et al. Exp Hematol 2012; March 6. [Epub ahead of print.]
2. Omontys Prescribing Information. Palo Alto, CA: Affymax, Inc.; March 2012.
3. Macdougall IC, et al. Dose-finding study of peginesatide for anemia correction in chronic kidney disease patients. Clin J Am Soc Nephrol 2011;6:2579-2586.
4. Macdougall IC, et al. A peptide-based erythropoietin-receptor agonist for pure red-cell aplasia. N Engl J Med 2009;361:1848-1855.
5. AFFY Affymax – Peginesatide's Risk/Benefit Ratio Does Not Support Approval. FDA Tracker. Available at: http://www.fdatracker.com/2011/11/14/affy-affymax-peginesatides-riskbenefit-ratio-does-not-support-approval/. Accessed April 24, 2012.
6. Affymax and Takeda report additional phase 3 clinical trial data for peginesatide in dialysis patients at the National Kidney Foundation spring clinical meetings. Available at: http://www.takeda.com/press/ article_40784.html. Accessed April 28, 2012.
A completely synthetic, once-monthly, erythropoiesis-stimulating agent has been approved for the treatment of anemia in dialysis patients.Subscribe Now for Access
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