Three-year safety observation of subcutaneous administration of epoetin-zeta in patients with chronic renal anemia: Results from PASCO II study.

Epoetin has been used to treat patients with renal anemia since 1988. -Anti-erythropoietin antibody-mediated pure red cell aplasia (PRCA) has been associated with epoetin usage, and a PRCA incidence of 4.5 per 10,000 patient-years was observed for epoetin-α (Eprex) in 2002. The PASCO II study (post-authorization safety cohort observation of Retacrit and Silapo (epoetin-ζ) administered subcutaneously for the treatment of renal anemia) followed 6,346 patients (4,501 Retacrit (group R); 1,845 Silapo (group S)) for up to 3 years of subcutaneous treatment with the biosimilar epoetin-ζ. One PRCA in 1 (0.02%) patient in group R who tested positive for neutralizing antibodies was reported. Overall, 527 adverse events of special interest (AESI) including PRCA occurred in 418 (6.60%) patients, lack of efficacy occurred in 34 (0.54%), and thromboembolic events in 389 (6.14%) patients. 41 adverse drug reactions other than AESIs were reported in 28 (0.44%) patients. The exposure-adjusted incident rate of PRCA was 0.84 per 10,000 patient-years. This real-world study showed that among patients with renal anemia receiving subcutaneous administration of the biosimilar product epoetin-ζ, the incidence rate of PRCA was substantially below the risk observed in 2002 for Eprex and that there was no immunogenicity concern or other new safety concern.

Results from a safety cohort of patients with renal anemia receiving the biosimilar epoetinzeta: The PASCO I study.

BACKGROUND: Epoetin-zeta (epoetin-ζ) (sold as Retacrit™/Silapo™) is a biologic product that was approved by the European Medicines Agency in 2007 after demonstrating biosimilarity to its reference product epoetin-α (Eprex™), based on a comprehensive comparability exercise including extensive biophysical characterization and three double-blind randomized controlled trials. Since 2008, epoetin-ζ has been prescribed by physicians across Europe to treat anemia of renal disease in many thousands of patients. METHODS: Provided here are results of the PASCO I study (post-authorization safety cohort observation of silapo/retacrit (epoetin-ζ) administered intravenously for the treatment of renal anemia). The primary study endpoint was the frequency of adverse events of special interest (AESI) occurring in patients receiving epoetin-ζ over a 1-year study observation period. RESULTS: The safety set included 1,634 patients who received at least 1 dose of epoetin-ζ during the study period. These patients experienced AESI at these frequencies: clotting of artificial kidney 9.8%, lack of efficacy 2.3%, cerebrovascular events (including cerebrovascular accident, cerebral infarction, cerebral hemorrhage, and transient ischemic attack) 1.8%, myocardial infarction 1.7%, acute myocardial infarction 1.2%, clinically relevant hyperkalemia 0.4%, deep vein thrombosis 0.2%, convulsion 0.2%, hypertensive encephalopathy 0.1%, and pulmonary embolism 0.1%. No patients were reported as having anaphylactoid reactions, angioedema, erythropoietinneutralizing antibodies, or pure red cell aplasia. The median weekly follow-up dose of epoetin-ζ was 158.6 IU/kg. Mean hemoglobin concentration ranged between 11.3 and 11.7 g/dL. From the safety set, 228 patients died (14.0%), while 1,135 patients (74.9%; excluding 119 with data missing) continued treatment with epoetin-ζ following the 12-month observation. CONCLUSION: The PASCO I study contributes significantly to current knowledge about the frequency of adverse events associated with the use of epoetin-ζ for the treatment of renal anemia and demonstrates a pattern of adverse events comparable with data for other existing epoetin products in Europe.