Biosimilar erythropoietin in anemia treatment (BEAT)—Efficacy and safety of a 1:1 dose conversion from EPREX® to EPIAO® in patients with end-stage renal disease on hemodialysis: A prospective, randomized, double blind, parallel group study

Abstract

Background: EPREX®/ERYPO®/PROCRIT® (epoetin alfa, Janssen-Cilag GmbH) was the first available recombinant human erythropoietin (rHuEPO) and was universally reference product as per the recommendation provided by European Medicines Agency. EPIAO® is a biosimilar formulation of EPREX®, and making it a 1:1 dose conversion from EPREX® according to recommendation of European Medicines Agency. This study evaluated the clinical efficacy and safety of EPIAO® in subjects with end-stage renal disease receiving hemodialysis after intravenous administration. Methods: This study was a multicenter, prospective, randomized, double-blind, parallel-group, 2-cohort, maintenance phase, therapeutic equivalence study to evaluate a 1:1 dose conversion from EPREX® to EPIAO® in terms of clinical efficacy and safety that was conducted at 20 sites in 2 countries in patients with end-stage renal disease on hemodialysis. Eligible subjects were treated with EPREX® (reference product of epoetin) for a period of at least 3 months before the treatment period, and then were randomly assigned to the group of EPREX® or EPIAO®. Primary endpoints were mean absolute change in hemoglobin level and mean absolute change in weekly epoetin dosage from baseline to 6 months after treatment with EPIAO®/EPREX® in parallel groups. Results: A total of 200 people received the random intervention and were included in the safety set. After 6, 9, and 12 months of treatment with EPIAO® or EPREX®, there were no significant differences in the hemoglobin levels of the 2 groups compared with baseline. The 95% confidence interval for the treatment difference was within the predetermined acceptable range: ±0.5 g/dL. There were no significant differences in the epoetin dosage of the 2 groups compared with the baseline. The 95% confidence interval for the treatment difference was within the predetermined acceptable range: ± 45 IU/kg. There were no significant differences in the incidence of adverse events between the EPIAO® and EPREX® groups. Most adverse events were mild to moderate and were reverted/resolved. Conclusion: EPIAO® demonstrated promising effectiveness and manageable safety in patients with end-stage renal disease on hemodialysis.

Development and qualification of a high-yield recombinant human Erythropoietin biosimilar

“…(5) Several clinical studies did not find any significant differences between pharmacokinetic and pharmacodynamic properties for different rhEPO [60][61][62][63][64][65][66]. ( 6) Confident glycoform analysis is a very critical process, and multiple parallel methods are preferred for obtaining confident PTM profiles using mass spectrometry analysis [67,68], which might not be supportive for cost-benefit perspective.…”

Satisfying QTPP of Erythropoietin Biosimilar by QbD through DoE-Derived Downstream Process Engineering

“…Despite having differences in sugar profile, there were no significant differences reported for in vivo biofunctionality for several preparations (12 different sources) of rhEPO [ 49 ]. Several clinical studies also did not reveal any significant differences between pharmacokinetic and pharmacodynamic properties for different rhEPO [ 50 , 51 , 52 , 53 , 54 , 55 , 56 ]. Secondly, confident glycoform analysis is a very critical process, and multiple parallel methods are preferred for obtaining confident PTM profiles using mass spectrometry analysis [ 56 , 57 , 58 ].…”