Erysaa

Erysaa Mechanism of Action

epoetin alfa

Manufacturer:

Duopharma (M)

Distributor:

DKSH
Full Prescribing Info
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Pharmacology: Pharmacodynamics: ERYSAA stimulates erythropoiesis by the same mechanism as endogenous erythropoietin.
ERYSAA (Epoetin alfa) obtained by gene technology is glycosylated and is identical in its amino acid and carbohydrate composition to endogenous human erythropoietin that has been isolated from the urine of anaemic patients.
ERYSAA has the highest possible purity according to the latest state of the art technology. In particular, no residues of the cell line used for the production are detectable at the concentrations of the active ingredient that are used in humans.
Healthy volunteers: After single I.V. bolus (100 IU/kg) of ERYSAA, the pharmacodynamic marker reticulocyte was investigated. ERYSAA increases the reticulocyte count within 7 days of initiation as similar to the pharmacodynamic profile of reference medicinal product Eprex.
Phase I study (PG-EPO-Ph1) in healthy subjects provided comparative pharmacodynamic data on ERYSAA versus Eprex. For 27 subjects who completed the study per protocol, the blood levels of RBC, haemoglobin, haematocrit and reticulocyte were determined up to 28 days following single-dose intravenous administration of Eprex or ERYSAA at an IV bolus dose of 100 IU/kg. The key PD parameters of absolute reticulocyte count were calculated as follows: median Tmax was 7 days for both Eprex and ERYSAA. Emax was 95.4(±21.7)*103/μL and 93.4(±24.2) *103/μL for Eprex and ERYSAA, respectively and AUEClast was 1773.6(±404.0) *103/μL*day and 1832.6(±414.4) *103/μL*day for Eprex and ERYSAA, respectively. The point-estimates and 90% CIs for both Emax GMR (test/reference) and AUEClast GMR (test/reference) lie within the equivalence margin of 0.8~1.25 and thus fulfill the criteria for PD comparability between ERYSAA and Eprex.
Clinical Trials: The multi-center, multi-national, double-blind, randomized, active controlled, parallel-group Phase III study (PG-EPO-Ph3) was conducted in a total of 298 Malaysian and Korean subjects where both populations were exposed to treatment of the product. The 2000 IU/0.5ml strength was tested during the study and showed therapeutic equivalence with the reference product Eprex so similar clinical effect can be expected on the hemoglobin levels of patients. The study design also includes exposure to the ERYSAA of up to 12-months during the open label phase to assess the long-term immunogenicity safety (see Adverse Reactions).
Pharmacokinetics: Healthy volunteers: After single I.V. bolus (100 IU/kg) of ERYSAA was observed for their plasma erythropoietin concentrations determined up to 24 hours. Measurement of epoetin alfa following single dose intravenous administration revealed a half-life of approximately 7 hours in normal volunteers.
A Phase I study (PG-EPO-Ph1) in healthy subjects provided pharmacokinetic (PK) data on ERYSAA in comparison to Eprex. In that study, 27 individual subjects completed the study per protocol and had their plasma erythropoietin concentrations determined up to 24 hours following single-dose intravenous administration of Eprex or ERYSAA at an IV bolus dose of 100 IU/kg. The key PK parameters of plasma erythropoietin concentration were calculated as follows: Tmax was 0.083 hours for both Eprex and ERYSAA treatment groups. Cmax was 2518.50(±269.30) mIU/mL and 2531.21(±272.50) mIU/mL for Eprex and ERYSAA, respectively, and AUClast was 17094.51(±2141.31) hr*mIU/mL, and 16464.51(±1872.40) hr*mIU/mL for Eprex and ERYSAA, respectively. In addition, respective CL values for Eprex and ERYSAA were 0.41(±0.06) L/hr and 0.42(±0.04) L/hr. The point-estimates and 90% CIs for both Cmax geometric mean ratio (GMR) (test/reference) and AUClast GMR (test/reference) lie within the equivalence margin of 0.8~1.25 and thus fulfill the criteria for PK comparability between ERYSAA and Eprex.
Toxicology: Preclinical Safety Data: Single Dose Toxicity: No single dose toxicity studies were performed. According to literature data, the highest epoetin alfa dose tested was > 40 times the highest human dose administered clinical today (600 IU/kg).
Repeated Dose Toxicity: In accordance with the guidelines on the evaluation of biosimilar products, a repeat-dose toxicity study with 2-week recovery was conducted in one animal species with 2 different dosages (100 IU/kg and 500 IU/kg) administered daily for 28 days to examine and compare the safety of study drug ERYSAA and comparator drug Eprex. The results demonstrated that two drugs were not different in terms of toxicity. And during the test period, no death occurred in either males or females.
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