Epoetin Delta Research Articles

Short-acting erythropoiesis-stimulating agents for anaemia in predialysis patients.

The benefits of erythropoiesis-stimulating agents (ESA) for chronic kidney disease (CKD) patients have been previously demonstrated. However, the efficacy and safety of short-acting epoetins administered at larger doses and reduced frequency as well as of new epoetins and biosimilars remains uncertain. This review aimed to evaluate the benefits and harms of different routes, frequencies and doses of epoetins (epoetin alpha, epoetin beta and other short-acting epoetins) for anaemia in adults and children with CKD not receiving dialysis. We searched the Cochrane Kidney and Transplant Specialised Register to 12 September 2016 through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. We included randomised control trials (RCTs) comparing different frequencies, routes, doses and types of short-acting ESAs in CKD patients. Two authors independently assessed study eligibility and four authors assessed risk of bias and extracted data. Results were expressed as risk ratio (RR) or risk differences (RD) with 95% confidence intervals (CI) for dichotomous outcomes. For continuous outcomes the mean difference (MD) with 95% confidence intervals (CI) was used. Statistical analyses were performed using the random-effects model. We identified 14 RCTs (2616 participants); nine studies were multi-centre and two studies involved children. The risk of bias was high in most studies; only three studies demonstrated adequate random sequence generation and only two studies were at low risk of bias for allocation concealment. Blinding of participants and personnel was at low risk of bias in one study. Blinding of outcome assessment was judged at low risk in 13 studies as the outcome measures were reported as laboratory results and therefore unlikely to be influenced by blinding. Attrition bias was at low risk of bias in eight studies while selective reporting was at low risk in six included studies.Four interventions were compared: epoetin alpha or beta at different frequencies using the same total dose (six studies); epoetin alpha at the same frequency and different total doses (two studies); epoetin alpha administered intravenously versus subcutaneous administration (one study); epoetin alpha or beta versus other epoetins or biosimilars (five studies). One study compared both different frequencies of epoetin alpha at the same total dose and at the same frequency using different total doses.Data from only 7/14 studies could be included in our meta-analyses. There were no significant differences in final haemoglobin (Hb) levels when dosing every two weeks was compared with weekly dosing (4 studies, 785 participants: MD -0.20 g/dL, 95% CI -0.33 to -0.07), when four weekly dosing was compared with two weekly dosing (three studies, 671 participants: MD -0.16 g/dL, 95% CI -0.43 to 0.10) or when different total doses were administered at the same frequency (four weekly administration: one study, 144 participants: MD 0.17 g/dL 95% CI -0.19 to 0.53).Five studies evaluated different interventions. One study compared epoetin theta with epoetin alpha and found no significant differences in Hb levels (288 participants: MD -0.02 g/dL, 95% CI -0.25 to 0.21). One study found significantly higher pain scores with subcutaneous epoetin alpha compared with epoetin beta. Two studies (165 participants) compared epoetin delta with epoetin alpha, with no results available since the pharmaceutical company withdrew epoetin delta for commercial reasons. The fifth study comparing the biosimilar HX575 with epoetin alpha was stopped after patients receiving HX575 subcutaneously developed anti-epoetin antibodies and no results were available.Adverse events were poorly reported in all studies and did not differ significantly within comparisons. Mortality was only detailed adequately in four studies and only one study included quality of life data. Epoetin alpha given at higher doses for extended intervals (two or four weekly) is non-inferior to more frequent dosing intervals in maintaining final Hb levels with no significant differences in adverse effects in non-dialysed CKD patients. However the data are of low methodological quality so that differences in efficacy and safety cannot be excluded. Further large, well designed, RCTs with patient-centred outcomes are required to assess the safety and efficacy of large doses of the shorter acting ESAs, including biosimilars of epoetin alpha, administered less frequently compared with more frequent administration of smaller doses in children and adults with CKD not on dialysis.

Developing glycoproteomic analysis of erythropoietin: towards discovering biomarkers for drug abuse

IntroductionErythropoietin is a glycoprotein hormone that is responsible for regulating the synthesis of red blood cells. Unfortunately, the ability of recombinant human EPO (rhEPO) to enhance haematopoiesis which increases the tissue oxygenation has led to its abuse in sports. The identification of rhEPO is very challenging due to its high similarity with endogenous EPO. EPO and rhEPO have high diversity of glycoforms that have different but overlapped pI. Currently, the standard procedure to detect EPO abuse in urine and blood samples is still utilising gel-based tools which have consistency and sensitivity issues. Glycoproteomic mass spectrometry on the other hand is the new approach in the search for biomarkers to differentiate recombinant EPO from the endogenous one. However, there is still a big gap of knowledge on the glycosylations of EPO that requires extensive profiling. ObjectiveTo perform glycoproteomic profiling of endogenous and recombinant EPO. MethodsNanoLC-Orbitrap-MS/MS was performed on endogenous (uEPO) and several rhEPO (BRP, Mircera, NESP, and Epoetin Delta). The liquid chromatogram was used to illustrate the variations between the molecules in their glycopeptides/peptide retention patterns. Mass spectral data was submitted to a bioinformatic platform for peptide and glycosylation de novo sequencing.MALDI-qTOF-MS/MS was also employed in parallel for glycosylation profiling. Results & DiscussionBRP showed a similar chromatographic pattern as uEPO except for a few distinct peaks. PEGlylated EPO Mircera showed two different regions of chromatographic peaks because the hydrophobic PEGylated peptides were retained longer than the non-PEGlyated peptides. Epoetin Delta and NESP showed even greater variation in the chromatographic pattern compared to uEPO believed to be due to differences in glycosylations and peptide sequence, respectively. Meanwhile, MALDI mass spectrum differential analysis enables the determination of sugar residues attachment to BRP. ConclusionGlycoproteomic mass spectrometric profiling holds the key to better discrimination between endogenous and recombinant EPO for anti-doping purposes.

Effect of single doses of methoxypolyethylene glycol‐epoetin beta (CERA, Mircera™) and epoetin delta (Dynepo™) on isoelectric erythropoietin profiles and haematological parameters

Erythropoietin (EPO) has been misused in sports for many years due to its performance-enhancing effect. In the last decade, detection of abuse has been possible with isoelectric focusing (IEF) based on the different isoform profiles of endogenous and recombinant EPO. The release of new EPOs on the market, such as the recombinant erythropoietin epoetin delta (Dynepo™) and the chemically modified EPO, CERA (Mircera™) potentially represents analytical challenges to the fight against doping. This study set out to investigate the possibility of and the time window for detecting the administration of a single dose of Dynepo™ and CERA. Our results are in agreement with earlier findings that detection of Dynepo™ is best achieved by combining IEF with SDS-PAGE. Haematological parameters were monitored for possible effects due to the long half-life (130 hours) of CERA in blood. Interestingly, although several haematological parameters were significantly changed after the injection of CERA, the endogenous EPO signal was still present in all collected samples. Due to the long half-life and the large size of the CERA molecule (about 60 kDa), it was uncertain whether CERA would be excreted into urine in detectable amounts unless urine collection was preceded by strenuous physical exercise. We find that CERA can be detected in urine without prior exercise in several, but not all, subjects. CERA is nevertheless best detected in serum with regard to both probability and length of detection, in addition to stability in matrix over time.

Defending Dynepo detection

Doping analysis as the detection of prohibited substances in an athlete's bodily specimen is not solely a scientific task; anti-doping scientists are challenged by the athlete's experts and have to defend their results in front of arbitration panels such as the Court of Arbitration in Sports (CAS). Compliance with the internationally accepted standards issued by the World Anti-Doping Agency (WADA) is commonly the main aspect to prove and demonstrate. Taking the example of four cases of doping with Epoetin delta (Dynepo) in endurance disciplines like marathon, triathlon, and cycling, the challenges and experiences in court and the argumentation lines of the defence experts are discussed. In all cases, doping with Epoetin delta was detected by two methods: isoelectric focusing (IEF) and SDS-PAGE. Epoetin delta is known to be produced in a human fibrosoma cell line. The slightly more abundant bands alpha and beta result in a short detection window using IEF analysis alone. With the additional complementary information obtained by SDS-PAGE analysis, data interpretation and defence in court is facilitated.

Quality of Original and Biosimilar Epoetin Products

PurposeTo compare the quality of therapeutic erythropoietin (EPO) products, including two biosimilars, with respect to content, aggregation, isoform profile and potency.MethodsTwo original products, Eprex (epoetin alfa) and Dynepo (epoetin delta), and two biosimilar products, Binocrit (epoetin alfa) and Retacrit (epoetin zeta), were compared using (1) high performance size exclusion chromatography, (2) ELISA, (3) SDS-PAGE, (4) capillary zone electrophoresis and (5) in-vivo potency.ResultsTested EPO products differed in content, isoform composition, and potency.ConclusionOf the tested products, the biosimilars have the same or even better quality as the originals. Especially, the potency of originals may significantly differ from the value on the label.

Differential Modulation of Angiogenesis by Erythropoiesis-Stimulating Agents in a Mouse Model of Ischaemic Retinopathy

BackgroundErythropoiesis stimulating agents (ESAs) are widely used to treat anaemia but concerns exist about their potential to promote pathological angiogenesis in some clinical scenarios. In the current study we have assessed the angiogenic potential of three ESAs; epoetin delta, darbepoetin alfa and epoetin beta using in vitro and in vivo models.Methodology/Principal FindingsThe epoetins induced angiogenesis in human microvascular endothelial cells at high doses, although darbepoetin alfa was pro-angiogenic at low-doses (1–20 IU/ml). ESA-induced angiogenesis was VEGF-mediated. In a mouse model of ischaemia-induced retinopathy, all ESAs induced generation of reticulocytes but only epoetin beta exacerbated pathological (pre-retinal) neovascularisation in comparison to controls (p<0.05). Only epoetin delta induced a significant revascularisation response which enhanced normality of the vasculature (p<0.05). This was associated with mobilisation of haematopoietic stem cells and their localisation to the retinal vasculature. Darbepoetin alfa also increased the number of active microglia in the ischaemic retina relative to other ESAs (p<0.05). Darbepoetin alfa induced retinal TNFα and VEGF mRNA expression which were up to 4 fold higher than with epoetin delta (p<0.001).ConclusionsThis study has implications for treatment of patients as there are clear differences in the angiogenic potential of the different ESAs.

Sciatic Nerve of Diabetic Rat Treated With Epoetin Delta: Effects on C-Fibers and Blood Vessels Including Pericytes

In diabetes mellitus (DM) reduced motor and sensory properties of peripheral nerves are linked with the dysfunction of neural vasculature. We investigated C-fibers and microvessels of sciatic nerve of normal, DM, and DM + epoetin delta-treated rats. C-fibers immunoreactive for calcitonin gene-related peptide (CGRP), tyrosine hydroxylase (TH), epoetin receptor (EpoR), and common beta receptor subunit of the interleukin 3 receptor (IL-3Rbeta) were present in all rats, whereas in DM and epoetin-treated rats C-fibers also showed neuronal (nNOS) and inducible (iNOS) nitric oxide synthases. The cross-sectional area of CGRP-positive C-fibers was decreased in DM, but it recovered after epoetin treatment. In all conditions, vascular endothelium showed scarce immunolabeling for endothelial nitric oxide synthase (eNOS); the profound immunoreactivity for eNOS, EpoR, and IL-3Rbeta was in pericytes. Some perivascular autonomic nerves were damaged and IL-3Rbeta positive. Findings are discussed in terms of declined sensory conduction velocity in DM, its improvement after epoetin treatment, and the possible vascular contribution to these phenomena.

Epoetin Delta as an Antifibrotic Agent in the Remnant Kidney Rat: A Possible Role for Transforming Growth Factor Beta and Hepatocyte Growth Factor

Background/Aims:Erythropoiesis-stimulating agents (ESAs) may have therapeutic benefits beyond ameliorating anemia. Although ESAs have renoprotective effects in acute/chronic renal injury models, their effects on blood pressure could also worsen chronic renal failure (CRF). The development of human cell-derived erythropoietin analogue epoetin delta prompted us (1) to investigate whether in a 5/6th nephrectomy-induced CRF rat model, epoetin delta-mediated renoprotective effects occur independently of its hematopoietic effects and (2) to unravel the involvement of particular factors herein. Methods: After induction of CRF in Wistar rats, epoetin delta was administered for 8 weeks at different doses: 0 IU/kg (uremic control); 48, 100 or 300 IU/kg 1×/week, and 16 or 100 IU/kg 3×/week. During this period hematopoietic and renal functional parameters as well as systolic blood pressure (SBP) were monitored. Results: After 8 weeks, control CRF rats showed reduced hematocrit (Hct)/hemoglobin (Hb) levels and increased SBP. Epoetin delta dose-dependently attenuated the reduction in Hct/Hb. Furthermore, epoetin delta treatment resulted in reduced deterioration of renal function in CRF rats after 8 weeks which was accompanied by decreased collagen deposition, renal fibrosis and interstitial macrophage infiltration. Remarkably, these renoprotective effects did not show the same dose dependency as compared to that seen for the hematopoietic response and were also seen at subhematopoietic doses. Interestingly, epoetin delta treatment resulted in a dose-dependent decrease of profibrotic (TGF-β) and proapoptotic (Bcl-2-associated X protein) genes together with a significant dose-dependent increase of antifibrotic (hepatocyte growth factor) and antiapoptotic (Bcl-2) genes. Epoetin delta treatment had no effect on VEGF expression. Conclusion: Epoetin delta treatment could delay the progression of CRF through antiapoptotic and antifibrotic mechanisms. This protective action of epoetin delta on the kidney probably is not directly related to its hematopoietic effects.

2009

The recombinant human erythropoietins and allied proteins (epoetin alfa, attempted copies and biosimilar variants of epoetin alfa, epoetin beta, epoetin delta, epoetin zeta, epoetin theta, epoetin omega, darbepoetin alfa, and methoxy-polyethylene glycol-epoetin beta) are among the most successful and earliest examples of biotechnologically manufactured products to be used in clinical medicine. This article charts a brief history of their use in clinical medicine, mainly dealing with chronic kidney disease, paying special attention to how these agents were introduced into clinical medicine and what has happened subsequently; in 2009, there were several developments that could be regarded as a "perfect storm" in terms of the long-term use of these compounds in chronic kidney disease and oncology and, likely, elsewhere. We are now very much at a "crossroads," where mature reflection is required, because with the latest trials and meta-analyses, these therapies seem not only expensive but also very much a clinical tradeoff (increased risk of adverse effects versus a small gain in fatigue scores). How we arrived at this crossroads is a useful illustration of how easy it is, without properly designed randomized, controlled trials, to assume that clinical benefit must follow therapeutic interventions.

Low-dose erythropoietin inhibits oxidative stress and early vascular changes in the experimental diabetic retina

Diabetic retinopathy is the result of increased oxidative and nitrosative stress induced by chronic hyperglycaemia, and affects the vasculature and the neuroglia. Erythropoietin is a neuroprotective and an endothelial survival factor. We assessed the effect of suberythropoietic epoetin delta doses on variables of oxidative stress in target tissues of diabetic complications and on pericyte loss in the diabetic retina. We administered epoetin delta to streptozotocin-induced diabetic Wistar rats at doses of 384 IU/kg body weight once weekly or 128 IU/kg body weight three times a week. The treatment lasted for 3 months. Oxidative stress and formation of AGEs were assessed by immunoblotting, expression of Ang-2 (also known as Angpt2) by RT-PCR, activation of protein kinase B (AKT) and heat shock protein (HSP)-27 levels by immunofluorescence, and incipient retinal vascular changes by quantitative morphometry of retinal digest preparations. Diabetes increased variables of oxidative stress and nitrosative stress (N(epsilon)-carboxymethyl-lysine, nitrotyrosine and methylglyoxal-type AGEs) in retina, kidney and heart of diabetic rats. Epoetin delta reduced oxidative and nitrosative stress in all tissues, and AGEs in the retina. It also reduced increased retinal Ang-2 expression and pericyte loss, and ameliorated p-AKT and HSP-27 levels. Epoetin delta has antioxidative properties in organs affected by diabetes and may prevent incipient microvascular damage in the diabetic retina.

Epoetin Delta Reduces Oxidative Stress in Primary Human Renal Tubular Cells

Erythropoietin (EPO) exerts (renal) tissue protective effects. Since it is unclear whether this is a direct effect of EPO on the kidney or not, we investigated whether EPO is able to protect human renal tubular epithelial cells (hTECs) from oxidative stress and if so which pathways are involved. EPO (epoetin delta) could protect hTECs against oxidative stress by a dose-dependent inhibition of reactive oxygen species formation. This protective effect is possibly related to the membranous expression of the EPO receptor (EPOR) since our data point to the membranous EPOR expression as a prerequisite for this protective effect. Oxidative stress reduction went along with the upregulation of renoprotective genes. Whilst three of these, heme oxygenase-1 (HO-1), aquaporin-1 (AQP-1), and B-cell CLL/lymphoma 2 (Bcl-2) have already been associated with EPO-induced renoprotection, this study for the first time suggests carboxypeptidase M (CPM), dipeptidyl peptidase IV (DPPIV), and cytoglobin (Cygb) to play a role in this process.

The Endothelium of Basilar Artery of Diabetic Rat Treated With Epoetin Delta

Erythropoiesis-stimulating agents (ESAs) are used to treat anemia associated with renal failure. It is now known that these agents also show a broad range of cell- and tissue-protective effects. In the current study, we explored whether an ESA, epoetin delta, affects vascular pathology linked to diabetes mellitus (DM). In a rat model of streptozotocin-induced DM, we investigated, by pre-embedding electron-immunocytochemistry, whether epoetin delta affects DM-induced structural changes in cerebrovascular endothelium of the rat basilar artery and influences the subcellular distribution of endothelial nitric oxide synthase (eNOS). Epoetin delta treatment influenced DM-induced changes to the distribution of eNOS in, and the structure of, the endothelial cell. This may indicate potential beneficial effects of epoetin delta on cerebrovascular endothelium and suggests eNOS as a possible target molecule of epoetin delta in DM.

Rx Report

Rx Report

Erythropoiesis Stimulating Agents and Techniques: A Challenge for Doping Analysts

Recombinant human erythropoietin (rHuEPO) engineered in Chinese hamster ovary (CHO) cell cultures (Epoetin alfa and Epoetin beta) and its hyperglycosylated analogue Darbepoetin alfa are known to be misused by athletes. The drugs can be detected by isoelectric focusing (IEF) and immunoblotting of urine samples, because "EPO" is in reality a mixture of isoforms and the N-glycans of the recombinant products differ from those of the endogenous hormone. However, there is a plethora of novel erythropoiesis stimulating agents (ESAs). Since the originator Epoetins alfa and beta are no longer protected by patent in the European Union, rHuEPO biosimilars have entered the market. In addition, several companies in Asia, Africa and Latin America produce copied rHuEPOs for clinical purposes. While the amino acid sequence of all Epoetins is identical, the structure of their glycans differs depending on the mode of production. Some products contain more acidic and others more basic EPO isoforms. Epoetin delta is special, as it was engineered by homologous recombination in human fibrosarcoma cells (HT-1080), thus lacking N-glycolylneuraminic acid like native human EPO. ESAs under development include EPO fusion proteins, synthetic erythropoiesis stimulating protein (SEP) and peptidic (Hematide(), CNTO 528) as well as non-peptidic EPO mimetics. Furthermore, preclinical respectively clinical trials have been performed with small orally active drugs that stimulate endogenous EPO production by activating the EPO promoter ("GATA-inhibitors": diazepane derivatives) or enhancer ("HIF-stabilizers": 2-oxoglutarate analogues). The prohibited direct EPO gene transfer may become a problem in sports only in the future.

Anaemia management with subcutaneous epoetin delta in patients with chronic kidney disease (predialysis, haemodialysis, peritoneal dialysis): results of an open-label, 1-year study

BackgroundAnaemia is common in patients with chronic kidney disease (CKD) and can be managed by therapy with erythropoiesis-stimulating agents (ESAs). Epoetin delta (DYNEPO®, Shire plc) is the only epoetin produced in a human cell line. The aim of this study was to demonstrate the safety and efficacy of subcutaneously administered epoetin delta for the management of anaemia in CKD patients (predialysis, peritoneal dialysis or haemodialysis)MethodsThis was a 1-year, multicentre, open-label study. Patients had previously received epoetin subcutaneously and were switched to epoetin delta at an identical dose to their previous therapy. Dose was titrated to maintain haemoglobin at 10.0–12.0 g/dL. The primary endpoint was mean haemoglobin over Weeks 12–24. Secondary analyses included long-term haemoglobin, haematocrit and dosing levels. Safety was assessed by monitoring adverse events, laboratory parameters and physical examinations.ResultsIn total 478 patients received epoetin delta, forming the safety-evaluable population. Efficacy analyses were performed on data from 411 of these patients. Mean ± SD haemoglobin over Weeks 12–24 was 11.3 ± 1.1 g/dL. Mean ± SD weekly dose over Weeks 12–24 was 84.4 ± 72.7 IU/kg. Haemoglobin levels were maintained for the duration of the study. Epoetin delta was well tolerated, with adverse events occurring at rates expected for a CKD patient population; no patient developed anti-erythropoietin antibodies.ConclusionSubcutaneously administered epoetin delta is an effective and well-tolerated agent for the management of anaemia in CKD patients, irrespective of dialysis status.Trial registrationhttp://www.controlled-trials.com ISRCTN68321818

Current and Upcoming Erythropoiesis-Stimulating Agents, Iron Products, and Other Novel Anemia Medications

Treatment for anemia has come a long way in the last 20 years since the first recombinant human erythropoietins were licensed for the management of anemia in chronic kidney disease. The first-generation epoetins were succeeded by the development and production of a longer-acting erythropoietin (EPO) analog, darbepoetin alpha, which allowed less frequent dosing, usually once weekly or once every 2 weeks. More recently, another EPO-related molecule has been manufactured called Continuous Erythropoietin Receptor Activator with an even longer half-life, and although for patent reasons this is not available in the United States, it is licensed and is already being used in Europe. Other molecules are in development or are becoming licensed in Europe, including biosimilar epoetin products/follow-on biologics, and elsewhere in the world there are cheaper-production "copy" epoetins. Indeed, it is estimated that up to 80 such products may be sold in countries with less stringent regulatory control of pharmaceutical products. Two different biosimilar epoetins have already been licensed in Europe, one under 2 different brand names and one under 3 different brand names, and others may follow. Hematide is a synthetic peptide-based EPO receptor agonist that, interestingly, has no structural homology with EPO, and yet is still able to activate the EPO receptor and stimulate erythropoiesis. This agent is currently in phase III clinical trials. Research continues for orally active antianemic therapies, and several strategies are being investigated, although none is imminently available. Two new intravenous iron preparations have recently been developed, one in the United States (Ferumoxytol; AMAG Pharmaceuticals, Inc., Cambridge, MA) and one recently licensed in Europe (ferric carboxymaltose [Ferinject; Vifor Pharma, Zurich, Switzerland]). In conclusion, the development of effective therapies for the treatment of anemia has been a highly active field, both scientifically and economically, over the last two decades.

Comments on Lundby et al.'s “Testing for recombinant human erythropoietin in urine: problems associated with current anti-doping testing”

to the editor: Ideally, anti-doping testing is designed to ensure fair competition and prevent athletes' harm from unfair practices. While the former issue is questionable, since fairness in sports is mostly a chimera, the latter is foremost and theoretically viable ([1][1]–[3][2]). The recent

Structural analysis of the glycosylation of gene-activated erythropoietin (epoetin delta, Dynepo)

Recently, a novel recombinant human erythropoietin (epoetin delta, Dynepo) has been marketed in the European Union for the treatment of chronic kidney disease, cancer patients receiving chemotherapy, and so forth. Epoetin delta is engineered in cultures of the human fibrosarcoma cell line HT-1080 by homologous recombination and “gene activation.” Unlike recombinant erythropoietins produced in other mammalian cells, epoetin delta is supposed to have a human-type glycosylation profile. However, the isoelectric focusing profile of epoetin delta differs from that of endogenous erythropoietin (both urinary and plasmatic). In this work, structural and quantitative analysis of the O- and N-glycans of epoetin delta was performed and compared with glycosylation from recombinant erythropoietin produced in Chinese hamster ovary (CHO) cells. From the comparison, significant differences in the sialylation of O-glycans were found. Furthermore, the N-glycan analysis indicated a lower heterogeneity from epoetin delta when compared with its CHO homologue, being predominantly tetraantennary without N-acetyllactosamine repeats in the former. The sialic acid characterization revealed the absence of N-glycolylneuraminic acid. The overall sugar profiles of both glycoproteins appeared to be significantly different and could be useful for maintaining pharmaceutical quality control, detecting the misuse of erythropoietin in sports, and establishing new avenues to link glycosylation with biological activity of glycoproteins.

Epoetin Delta: Efficacy in the Treatment of Anaemia in Cancer Patients Receiving Chemotherapy

Aims To assess the effect of epoetin delta on anaemia in patients with cancer who were receiving chemotherapy. Materials and methods This report includes data from two 12-week studies of epoetin delta: a randomised, double-blind, placebo-controlled study of three times weekly epoetin delta (150 or 300 IU/kg) and an open-label extension collecting further efficacy and safety information, in which patients initially received epoetin delta 150IU/kg. Co-primary end points for the double-blind study were an increase in haemoglobin levels and a reduction in the requirement for red blood cell transfusions compared with placebo. Results Double-blind study: 313 cancer patients were randomised to epoetin delta or placebo. Epoetin delta was associated with a significantly greater increase in haemoglobin levels from baseline compared with placebo (epoetin delta 150 and 300 IU/kg vs placebo: 2.5 and 2.5 g/dl vs 0.6 g/dl; P < 0.0001 for both comparisons), meeting one co-primary end point. However, there were no significant differences between groups in the proportion of patients requiring red blood cell transfusions (epoetin delta 150 and 300 IU/kg vs placebo: 26.0 and 21.9% vs 26.9%), the second co-primary end point. Open-label study: 149 patients entered the extension study. During the extension, haemoglobin levels were maintained and a higher proportion of patients who previously received placebo required transfusions than those who had previously received epoetin delta (previous epoetin delta 150 and 300 IU/kg: 7.1 and 11.4% vs previous placebo: 15.9%). Adverse events were as expected for this population in both studies. Conclusion Epoetin delta shows potential as a treatment for anaemia in cancer patients receiving chemotherapy.

On the detection of newer Epo forms in serum and urine using isoelectric focusing

American Journal of HematologyVolume 83, Issue 9 p. 754-755 LetterFree Access On the detection of newer Epo forms in serum and urine using isoelectric focusing Joris Delanghe, Corresponding Author Joris Delanghe [email protected] Department of Clinical Chemistry, University Hospital Ghent, BelgiumDepartment of Clinical Chemistry, University Hospital Ghent, BelgiumSearch for more papers by this authorMathieu Bollen, Mathieu Bollen Laboratory of Biosignaling and Therapeutics, Department of Molecular Cell Biology, KU Leuven, Leuven, BelgiumSearch for more papers by this authorMonique Beullens, Monique Beullens Laboratory of Biosignaling and Therapeutics, Department of Molecular Cell Biology, KU Leuven, Leuven, BelgiumSearch for more papers by this author Joris Delanghe, Corresponding Author Joris Delanghe [email protected] Department of Clinical Chemistry, University Hospital Ghent, BelgiumDepartment of Clinical Chemistry, University Hospital Ghent, BelgiumSearch for more papers by this authorMathieu Bollen, Mathieu Bollen Laboratory of Biosignaling and Therapeutics, Department of Molecular Cell Biology, KU Leuven, Leuven, BelgiumSearch for more papers by this authorMonique Beullens, Monique Beullens Laboratory of Biosignaling and Therapeutics, Department of Molecular Cell Biology, KU Leuven, Leuven, BelgiumSearch for more papers by this author First published: 27 May 2008 https://doi.org/10.1002/ajh.21228Citations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL References 1 Delanghe JR,Bollen M,Beullens M. Testing for recombinant erythropoietin. Am J Hematol 2008; 83: 237– 241. 2 Kwan JT,Pratt RD. The Epoeitin delta study group. Epoetin delta, erythropoietin produced in a human cell line, in the management of anaemia in predialysis chronic kidney disease patients. Curr Med Res Opin 2007; 23: 307– 311. 3 Peltre G,Thormann W. Evaluation Report of the Urine EPO Test. Paris: Council of the World Anti-Doping Agency (WADA); 2003. 4 Ketterer F. Die gehen da gezielt ran. Die Tageszeitung 2002. 5 Kohler M,Ayotte C,Desharnais P, et al. Discrimination of recombinant and endogenous urinary erythropoietin by calculating relative mobility values from SDS gels. Int J Sports Med 2008; 29: 1– 6. 6 Reicheil C. SDS-PAGE of recombinant and endogeneous erythropoietins: benefits and limitations of the method for application in doping control. Manfred Donike Workshop. 26th Cologne Workshop on Dope Analysis, 2008. Abstract. 7 Lamon S,Robinson N,Sottas PE, et al. Possible origins of undetectable EPO in urine samples. Clin Chim Acta 2007; 385: 61– 66. 8 Franke WW,Heid H. Pitfalls errors and risks of false-positive results in urinary EPO drug tests. Clin Chim Acta 2006; 373: 189– 190. 9 Lasne F,Martin L,Martin JA,de Ceaurriz J. Isoelectric profiles of human erythropoietin are different in serum and urine. Int J Biol Macromol 2007; 41: 354– 357. 10 Mallorqui J,Segura J,de Bolos C, et al. Recombinant erythropoietin found in seized blood bags from sportsmen. Haemotologica 2008; 93: 313– 314. 11 Skibeli V,Nissen-Lie G,Torjesen P. Sugar profiling proves that human serum erythropoietin differs from recombinant human erythropoietin. Blood 2001; 98: 3626– 3634. 12 Kung CK,Goldwasser E. A probable conformational difference between recombinant and urinary erythropoietins. Proteins 1997; 28: 94– 98. 13 Wide L,Bengtsson C,Berglund B,Ekblom B. Detection in blood and urine of recombinant erythropoietin administered to healthy men. Med Sci Sports Exerc 1995; 27: 1569– 1576. Citing Literature Volume83, Issue9September 2008Pages 754-755 ReferencesRelatedInformation