what is the difference between erythropoietin and darbepoetin

what is the difference between erythropoietin and darbepoetin
October 28, 2020

This illustrates that structural changes may exist between two similar drugs, however, there is currently little understanding of how these changes may impact safety, efficacy, or immunogenicity and thus, extensive in vivo testing will be necessary to establish comparability. Patients who develop neutralizing anti-erythropoietin antibodies are at risk for pure red cell aplasia (PRCA), which can require red blood cell transfusions.

However, only limited information is available on the economic comparability of epoetin alpha, epoetin beta and darbepoetin alpha, and thus this study was conducted to compare cost per patient of each of these agents for anaemic cancer patients. The first biosimilar rHuEPO to receive EMEA marketing authorization was Binocrit in 2007 (epoetin α, Sandoz GmbH, Austria) and this was developed as a biosimilar form of Eprex (Janssen-Cilag). rHuEPOα forms a four-helix bundle structure linked by two less structured loops and the ternary structure is stabilized by two disulfide bridges.

Epoetin alfa is used to treat nonregenerative anemia.

The finding of a cost difference favouring epoetin alpha over darbepoetin alpha suggests the need for prospective randomized studies comparing efficacy and cost effectiveness of all three agents to obtain more definitive data. Pharmacokinetics of novel erythropoiesis stimulating protein compared with epoetin alfa in dialysis patients. After subcutaneous administration the systemic availability of epoetin is not complete (20%) and lower plasma concentrations are observed than after intravenous administration. epoetin in a population of haemodialysis patients.

Please enable it to take advantage of the complete set of features! Ongkingco JR, Ruley EJ, Turner ME, Fragale MR. Efficacy of once‐ versus thrice‐weekly subcutaneous recombinant human erythropoietin in children receiving continuous cycling peritoneal dialysis.

doi: 10.3310/hta11130. Jones CH, Ridley L, Richardson D. Which EPO dose per week? The BP can usually be controlled with a combination of fluid removal with dialysis and conventional antihypertensive therapy. Provenzano R, Morrison L. Once‐weekly treatment with epoetin alfa in patients with anemia due to chronic kidney disease: preliminary analysis. Biosimilars are therapeutic products exhibiting comparable quality, safety and efficacy to an existing product, the patent of which has typically expired. Patients on twice‐ or thrice‐weekly epoetin were converted to once‐weekly darbepoetin alfa, and patients on once‐weekly epoetin were converted to darbepoetin alfa once every other week [18]. Proposed therapeutic algorithm for the treatment of anemia of chronic renal failure in pre‐dialysis patients with low dose weekly subcutaneous r‐HuEPO. As costs of the three agents in Austria are identical for therapeutically equivalent doses, the higher cost of darbepoetin alpha was believed to be due mainly to longer treatment duration to target haemoglobin level.

Epoetin has a half-life of about 4–6 hours, and is normally given two or three times a week.

Cheung W, Minton N, Gunawardena K. Pharmacokinetics and pharmacodynamics of epoetin alfa once weekly and three times weekly. What we are lacking now is a head‐to‐head study comparing once‐weekly epoetin with darbepoetin alfa. More recently, a European multicentre study showed similar results with both once‐weekly (n=54) and once‐fortnightly (n=74) s.c. administration of epoetin‐beta to peritoneal‐dialysis patients [24].

Cases of PRCA have developed as a consequence of antibody formation against endogenous erythropoietin or while receiving treatment with recombinant erythropoietin. According to the authors “a non-significant trend for decreased mortality in patients treated with darbepoetin with a similar adverse event profile compared to placebo was shown in one study; however, the largest trial to date showed no benefit in all-cause mortality or heart failure-related hospitalizations with the use of ESAs.” Additionally, a statistically significant increase in the number of cerebrovascular events and thrombotic events was found [114R,115r]. Thomas R. Gelzleichter, in Nonclinical Development of Novel Biologics, Biosimilars, Vaccines and Specialty Biologics, 2013. Effectiveness and safety of recombinant human erythropoietin in predialysis patients. Efficacy of recombinant human erythropoietin administered subcutaneously to CAPD patients once weekly.

Yagil Y. They were switched to once‐weekly administration, as in the Weiss study [22], and there was a significant fall in the mean haemoglobin over the subsequent 16 weeks despite a significant increase in epoetin dose. No such study has yet been published, and in the climate of evidence‐based medicine, purists might legitimately suggest that such a study is required to confirm or refute the hypothesis that once‐weekly darbepoetin alfa is more effective than once‐weekly epoetin treatment, due to its longer biological half‐life. Perioperative, high-dose EPO administration does not prevent delayed graft function in deceased donor kidney transplant.

It is possible that higher doses of epoetin may have to be used to obtain the same biological response, and this is of course also dependent on what conversion factor is used to compare epoetin with darbepoetin alfa. A randomized controlled trial comparing the pharmacokinetics and pharmacodynamics of epoetin‐alfa administered subcutaneously once weekly and three times weekly to 36 healthy adults was also reported last year [29], with similar pharmacodynamic responses seen in both groups despite differences in total erythropoietin exposure. The SPC for darbepoetin alfa suggests a conversion factor of 200 U of epoetin to 1 μg of darbepoetin alfa, but this ratio may alter, particularly at higher dosage levels.

Phlebotomy of 500 mL of blood may rapidly lower BP in refractory patients. If these measures are unsuccessful, the dose of r-HuEPO should be lowered or therapy should be held for several weeks. Systemic hypertension has been reported to develop, or to worsen, in 20% to 30% of patients treated with r-HuEPO worldwide.55 The greatest increases in BP affect daytime systolic and nighttime diastolic BP.1,2 Hypertension may develop in some patients as early as 2 weeks and in others as late as 4 months after the start of r-HuEPO treatment.1,2 Hypertension has not proved to be a serious general problem in the r-HuEPO treated patient; however, few cases of hypertensive crisis with encephalopathy have been reported.1,2, Several risk factors for the development, or worsening, of hypertension after r-HuEPO therapy, have been identified. All prescriptions of the agents over 1 year were analysed by two Austrian regional public health insurance associations and cost per patient for each agent was calculated from invoicing data. What has been well established is that modifications in glycosylation can greatly impact both drug clearance and receptor binding. Darbepoetin Alfa. HHS

Geddes C, Worjtzcak V, Adams A, McPherson M, French C. Does erythropoietin requirement increase with reduced frequency of administration? In children undergoing peritoneal dialysis, epoetin is usually given intraperitoneally, resulting in similar systemic availability and dosages compared with subcutaneous administration. Interim analysis has demonstrated that darbepoetin-alfa dosed every 2 or every 4 weeks has been effective for partial correction and/or maintenance of Hb with no indications of safety issues. Currently, three forms are marketed, including epoetin α (Epogen, Epogin, Eprex, and Procrit), epoetin β (NeoRecormon and Recormon), epoetin δ (Dynepo), and epoetin Ω (Epomax). It is certainly less common to start such patients on once‐weekly administration, although a large Austrian multicentre study in pre‐dialysis patients did utilize a treatment regimen of 10 000 U of epoetin once weekly [6]. In addition, darbopoietin is a hyperglycosylated mutant form of epoetin α with five amino acid changes that has been glycoengineered to extend serum half-life. Recombinant human EPOα is a 165-amino-acid single-polypeptide chain that contains three N-linked glycosylation sites at Asn24, Asn38, and Asn83 and one O-linked site at Ser126 [14]. 2007 Apr;11(13):1-202, iii-iv. A second hypothesis has been posed that leachates produced from uncoated rubber stoppers might provide an adjuvant effect and such leachates have been shown to increase antigenicity to ovalbumin in mice.

Conclusion:  |  Nissenson AR, Swan SK, Lindberg JS et al. Recombinant human erythropoietin (rHuEPO) has been shown to exert nephroprotective action in animal models.” A meta-analysis was conducted to explore the impact of rHuEPO on DGF in kidney transplant patients. Novel erythropoiesis stimulating protein. Given these properties, the control of glycosylation is highly critical in maintaining product quality. A similar agent used in animals is erythropoietin (epoetin alpha).

Lui SF, Wong KC, Li PK, Lai KN. Given that sialic acids contain negative charges, a negative electric field will grow as sialic acid content increases and this is thought to negatively impact receptor binding. With i.v. It has been used to treat myelosuppression caused by disease or chemotherapy. Epub 2018 Feb 14. Horl W. IV darbepoetin alfa is more effective than i.v. For this reason, early evaluation of comparative PK may prove a useful tool early on in cell line development and process refinement. Darbepoetin-alfa (Aranesp®, Amgen, Thousand Oaks, CA, USA) is a hyperglycosylated EPO analogue designed for prolonged survival in the circulation and with consequent greater bioavailability than epoetins. As glycan content increases, so too does the hydrodynamic diameter of EPO. Clipboard, Search History, and several other advanced features are temporarily unavailable. Stamm TA, Reichardt B, Zwerina J, Ritschl V, Nell-Duxneuner V. Wien Klin Wochenschr. Epoetin alfa (EPO) and darbepoetin alfa (DPO) are erythropoiesis-stimulating agents (ESAs) that are widely and interchangeably used for the treatment of anemia in patients with advanced chronic kidney disease and end-stage renal disease. In a further uncontrolled study, Simon Roger (personal communication) switched patients from epoetin‐alfa to darbepoetin alfa with a conversion factor of 200 U of epoetin to 1 μg of darbepoetin alfa. This property confers greater metabolic stability and a lower clearance rate in vivo, and the elimination half-life of this compound in humans after a single intravenous administration is three times greater than that of epoetin alfa (25.3 hours versus 8.5 hours). The second study (from Italy) [23] was a therapeutic‐equivalence study again comparing once‐weekly administration of epoetin‐beta with twice‐ or thrice‐weekly administration. Once‐weekly administration of both epoetin and darbepoetin alfa is possible provided the drug is given s.c. Your comment will be reviewed and published at the journal's discretion. therapy in haemodialysis patients and s.c. therapy in peritoneal dialysis patients. Vanrenterghem Y, Barany P, Mann J et al. [3] treated 10 CAPD patients with epoetin 100 U/kg/week either once or twice weekly, and equivalent haemoglobin responses and epoetin dose requirements were seen.

However, the apparent half-life of epoetin is prolonged after subcutaneous injection, and this allows the use of lower doses to obtain an equivalent hemoglobin concentration [38]. TABLE 7.2.

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