Study Demonstrates Real-World Safety, Effectiveness of Biosimilar Epoetin Alfa for Renal Anemia

Patients with renal anemia undergoing hemodialysis who were treated for up to 24 months with the intravenous biosimilar epoetin alfa HX575 (Binocrit) showed hemoglobin (Hb) outcomes equivalent to reference epoetin alfa, according to a study published in the January 2018 issue of Clinical Nephrology.

The study (MONITOR-CKD5) is the largest and longest study of a biosimilar epoetin alfa in the hemodialysis setting. It was funded by Hexal AG (Sandoz, Novartis). Binocrit, a product of Sandoz, was approved in the European Union in 2007 for the treatment of chemotherapy-induced anemia and anemia associated with chronic renal failure, and is a biosimilar of Epogen (Amgen) and Procrit (Janssen).

Gérard London, MD, and colleagues reported that the majority of treated patients in their study were maintained within guideline-recommended target Hb ranges, and no previously unknown safety signals, including immunogenicity, were detected.

The study was carried out in 114 centers in 10 European countries; of 2086 patients enrolled in the study, 1000 completed all follow-up visits and comprised the evaluable enrollment sample. The sample was predominantly male (median age of 68 years), and almost exclusively Caucasian. The most prevalent primary chronic kidney disease etiologies included diabetic nephropathy, chronic glomerulonephritis, and renal vascular disease. Median time on dialysis was 2.1 years.

At enrollment, most patients (82.5%) had been treated with an erythropoiesis-stimulating agent, and 73.0% had adequate iron stores. At baseline, mean (± standard deviation) baseline Hb was 11.09 (±1.14) g/dL and HX575 dose 106.5 (±78.7) International Units (IU)/kg/week; at month 24, Hb was 11.25 (±1.19) g/dL and HX575 dose was 113.0 (±102.5) IU/kg/week. Variations in mean HX575 dose and Hb over the study period were not statistically significant.

With respect to safety, 140 patients (6.7%) experienced 1 or more adverse event (AE); of these, 19 AEs (16 patients; 0.8%) were related to treatment with HX575; 148 AEs (108 patients; 5.2%) were reported as serious, including 12 events in 11 patients (0.5%) that were stated by the researchers as related to the drug. No cases of anti-epoetin antibodies or pure red cell aplasia were reported.

The researchers note that the current study demonstrates that the efficacy of intravenous HX575 in managing renal anemia in patients undergoing hemodialysis, which was established in earlier pivotal trials and validated in follow-on studies, translates into real-world effectiveness, with safety evidence extending up to 2 years. The study shows that Hb concentrations and treatment-response indicators converged across 3 critical HX575 studies, and under similar dosing regimens.

“Importantly, what our study adds is that this pattern of stable dosing and stable Hb effectiveness outcomes can be achieved sustainably for up to 24 months with HX575 under conditions of greater heterogeneity in patients, clinicians, and settings compared to the relative homogeneity that characterizes efficacy trials,” the authors said.

With the relative effectiveness and safety of HX575 established, the investigators conclude that policy, financing, and access to care issues related to the biosimilar can be addressed. “In an era of payment constraints to dialysis providers, the use of biosimilar epoetin alfa can generate significant savings.”