Biosimilarity of HX575 (human recombinant epoetin alfa) and epoetin beta after multiple subcutaneous administration

“…The higher dose requirements for the alfa preparation were supported by Halstenson and colleagues 7 who found in healthy volunteers that alpha epoetin had a larger volume of distribution than the beta preparation (16.9% vs. 7.7%), but that beta epoetin had a 20% longer half-life. More recent work by Sorgel and colleagues 8 has shown both products to be bioequivalent. They concluded that both are equally efficacious and could be used interchangeably.…”

Section: Discussionmentioning

confidence: 98%

“…The longitudinal and retrospective design of our study does not eliminate natural changes seen in disease progression and epoetin responsiveness. However, all previous work comparing these epoetin products have used cohorts of no larger than 80 individuals, 7,8 which makes our study one of the largest. As there are currently no large-scale randomized studies comparing these products on renal failure patients, we believe our findings support the need for these to be carried out.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Therapeutic Efficacy of Epoetin Beta and Epoetin Alfa in Maintenance Phase Hemodialysis Patients

2011

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In May 2009 for financial reasons, the epoetin product used for hemoglobin (Hb) maintenance in our renal dialysis unit was changed from epoetin beta to epoetin alfa. Although widely believed that the dosage requirements are the same, we undertook a retrospective analysis to investigate whether the dosage requirements in chronic renal failure patients were comparable for both preparations. We studied 128 stable end-stage renal failure patients on hemodialysis (three times per week) receiving erythropoietin therapy to maintain their Hb at 11-12.5 g/dL. Patients were excluded if within the study period they developed signs of infection, bleeding, required blood transfusion, were under-dialyzed, or required hospital admission. Regular monthly Hb concentrations and hematocrit (Hct) levels were measured for each patient. The weekly EPO index (defined as weekly epoetin dose/mean monthly Hct) was derived for each patient, before and after regime change. Of the 128 patients in end-stage renal failure, 79 were included in the study. There was no significant difference between the two preparations in terms of Hct level achieved (p = 0.15). However, the median weekly epoetin dose requirement increased from 6733 (range 750-30,000) IU/week to 9000 (250-30,667) IU/week (p < 0.001). EPO index similarly increased from 20,465 (2500-130,846) IU/week/% to 27,073 (729-98,937) IU/week/% (p < 0.001). Our study showed that a higher dose of epoetin alfa was needed to maintain target Hb concentration.

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“…Clinical studies compared the pharmacokinetic and pharmacodynamic properties of different strengths and administration routes of HX575 and Erypo®/Eprex® in healthy volunteers. [8,14,15] The efficacy and safety of HX575 in the treatment of patients with chronic kidney disease was assessed in comparison with Erypo®/Eprex®,[16] and further safety data were provided in a comparative study in patients experiencing chemotherapy-induced anemia. [17]…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Pharmacokinetic and Pharmacodynamic Profiles of One US-Marketed and Two European-Marketed Epoetin Alfas

2011

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Objectives: The aim of this study was to investigate the bioequivalence and potency of registered epoetin alfa products that have not been compared before in a randomized controlled clinical study.Methods: The study was conducted in two parts: part A compared the European-marketed HX575 and the US-marketed Epogen®; part B compared the European-marketed Erypo®/Eprex® and HX575 manufactured at two different drug substance production sites (HX575-TT denoting the already-approved technology-transfer product from an additional manufacturing site). In analyses across both study parts, Epogen® was exploratorily compared with Erypo®/Eprex®.A dense-sampling 48-hour pharmacokinetic profile was recorded at steady state after 11 doses of 100 IU epoetin alfa per kg of bodyweight. The hemoglobin response over 4 weeks of study medication administration was analyzed as the primary efficacy surrogate parameter using an ANCOVA model with the baseline value as co-variate.The per-protocol population comprised a total of 268 subjects, 76 in part A (equally randomized to HX575 or Epogen®) and 192 in part B (equally randomized to HX575, HX575-TT, or Erypo®/Eprex®). Pairs of study arms were compared in terms of the ratio of the mean epoetin alfa area under the curve (AUC) and the ratio of the mean hemoglobin area under the effect curve (AUEC).Results: Bioequivalence was shown in all pair-wise comparisons with the 90% confidence intervals of the AUC ratios falling within the standard bioequivalence limits of 80–125%. Moreover, an equivalent pharmacodynamic response was achieved with all compared epoetin alfa products, as confirmed by the hemoglobin AUEC ratio’s 90% CI falling within the predefined acceptance margins of 96.8–103.2%. Thus, bioequivalence and equivalent potency was demonstrated for HX575 and Epogen® in part A of the study, as well as for HX575, HX575-TT and Erypo®/Eprex® in part B of the study. Pair-wise comparison across study parts indicated similar pharmacokinetic and pharmacodynamic profiles of Epogen® and Erypo®/Eprex®.All compared epoetin alfa products were well tolerated and had a similar safety profile. No subject developed anti-erythropoietin antibodies upon administration of study medication.Conclusion: The results show, for the first time in a prospective randomized clinical study, equivalent bioavailability at steady state and similar potency of the US-marketed Epogen® and the European-marketed Binocrit®. Differences in the formulation between the epoetin alfa products had no apparent clinical impact. The high degree of similarity between Epogen® and Erypo®/ Eprex® provides justification for linking and comparing results from clinical studies that were conducted using either US- or European-marketed epoetin alfa products.

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Biosimilarity of HX575 (human recombinant epoetin alfa) and epoetin beta after multiple subcutaneous administration

Cited by 14 publications

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Epoetin Biosimilars in Europe: Five Years On

Epoetin Biosimilars in Europe: Five Years On

Comparison of the Therapeutic Efficacy of Epoetin Beta and Epoetin Alfa in Maintenance Phase Hemodialysis Patients

Comparison of the Pharmacokinetic and Pharmacodynamic Profiles of One US-Marketed and Two European-Marketed Epoetin Alfas

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