Cohort Prospective Study to Evaluate Immunogenicity of Epodion® (Biosimilar Epoetin-α) in Anemia Associated with Chronic Kidney Disease (CKD) Patients

Nova Angginy, Chang Woo Suh, Jonny Jonny, Nuly Juariah Mahnulia, Suhardjono Suhardjono


Background: Anemia due to chronic kidney disease (CKD) is often associated with decreased erythropoietin (EPO) levels in the blood. Treatments available are improving blood iron levels and administration of exogenous EPO (rhEPO). This study aims to assess the safety and immunogenicity of Epodion, a biosimilar rhEPO product, in haemodialysis patients with CKD-associated anaemia in three Indonesian hospitals.
Methods: This prospective, open label, single arm, and multicenter study enrolled patients with anemia associated with CKD under hemodialysis treatment. Patient eligibility was assessed within the 4-week screening period. Blood samples for determination of erythropoietin antibody (Anti-Drug Antibody) were taken at week-0, 24, and 52 using a validated and highly sensitive bridging ELISA method. Evaluation of Neutralizing Antibody (NAb) was carried out to confirm the impact of the antibody to pharmacological activity (e.g., antibody-mediated PRCA) when the ADA detection of patients was positive after screening and confirmatory assay. Results: Results from all tested patients show that Epodion could maintain hemoglobin and hematocrit levels. ADA detection using ELISA assay yielded negative results for all plasma samples of week-24 and week-52, so the evaluation of NAb was not carried out. No adverse events were considered relevant to tested product. Conclusion: This study proves no immunogenic effect of Epodion on stimulating immune system’s antibodies in Indonesian patients with CKD-associated anemia.


Anemia; anti-drug antibody; anti-rhEPO; chronic kidney disease; erythropoietin


Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3:1–150.

Kementerian Kesehatan RI. Situasi penyakit ginjal kronis. Jakarta: Pusat Data dan Informasi Kementrian Kesehatan RI; 2017.

Luyckx VA, Tonelli M, Stanifer JW. The global burden of kidney disease and the sustainable development goals. Bull World Health Organ. 2018;96(6):414-22.

Indonesian Ministry of Health. Basic health research report (In Bahasa: Riset Kesehatan Dasar). Jakarta; 2013.

Kalantar-Zadeh K. History of erythropoiesis-stimulating agents, the development of biosimilars, and the future of anemia treatment in nephrology. Am J Nephrol. 2017;45(3):235–47.

European Medicines Agency (EMA). Biosimilars in the EU: information guide for healthcare professionals. European Medicines Agency; 2017.

World Health Organization (WHO). Guidelines On evaluation of similar biotherapeutic products (SBPs). Geneva; 2009.

Food and Drug Administration (FDA). Immunogenicity testing of therapeutic protein products - developing and validating assays for anti-drug antibody detection. 2019.

Chow, SC. Biosimilars: design and analysis of follow-on biologics. CRC Press; 2013.

Krishna M, Nadler SG. Immunogenicity to biotherapeutics - The role of anti-drug immune complexes. Front Immunol. 2016;7(Feb).

Chirmule N, Jawa V, Meibohm B. Immunogenicity to therapeutic proteins: Impact on PK/PD and efficacy. AAPS J. 2012;14(2):296–302.

Grams ME, Yang W, Rebholz CM, et al. Risks of adverse events in advanced CKD: the chronic renal insufficiency cohort (CRIC) study. Am J Kidney Dis. 2017;70(3):337-46.

Hörl WH, Locatelli F, Haag-Weber M, Ode M, Roth K. Prospective multicenter study of HX575 (biosimilar epoetin-α) in patients with chronic kidney disease applying a target hemoglobin of 10 - 12 g/dl. Clin Nephrol. 2012;78(1):24–32.

London G, Mann J, Goldsmith D, et al. Long-term treatment with biosimilar epoetin-α (HX575) in hemodialysis patients with renal anemia: Real-world effectiveness and safety in the MONITOR-CKD5 study. Clin Nephrol. 2018;89(1):1–9.

Hustrini NM, Siregar P, Setiawati A, Nugroho P. Clinical comparison of Renogen, a biosimilar Epoetin-a, with the originator, eprex, in chronic kidney disease anemia in Indonesia: A preliminary study. Acta Med Indones. 2019;51(3):230–7.

Haag-Weber M, Eckardt KU, Hörl WH, Roger SD, Vetter A, Roth K. Safety, immunogenicity and efficacy of subcutaneous biosimilar epoetin-α (HX575) in non-dialysis patients with renal anemia: A multi-center, randomized, double-blind study. Clin Nephrol. 2012;77(1):8–17.

Casadevall N. Antibodies against rHuEPO: Native and recombinant. Nephrol Dial Transplant. 2002;17(Suppl. 5):42–7.

Shin SK, Moon SJ, Ha SK, et al. Immunogenicity of recombinant human erythropoietin in Korea: A two-year cross-sectional study. Biologicals [Internet]. 2012;40(4):254–61. Available from:

Phrommintikul A, Haas SJ, Elsik M, Krum H. Mortality and target haemoglobin concentrations in anaemic patients with chronic kidney disease treated with erythropoietin: a meta-analysis. Lancet. 2007;369(9559):381-8.

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