The FDA requested that Retacrit's maker provide data on subcutaneous administration, given that immunogenicity of a protein can be impacted by route of administration. Results from that study, newly published in Kidney International Reports, show that the subcutaneous administration of the biosimilar has similar safety and efficacy to subcutaneous administration of the reference (Epogen, Procrit).
When Pfizer’s biosimilar epoetin alfa, Retacrit, was approved in 2018, the FDA authorized the product on the basis of a comprehensive data package that included structural and functional characterization, pharmacokinetic and pharmacodynamic data, and data from a study of the drug administered intravenously to patients with anemia.
The FDA also requested that the drug maker provide data on subcutaneous administration, given that immunogenicity of a protein can be impacted by route of administration. Results from that study, newly published in Kidney International Reports, show that the subcutaneous administration of the biosimilar has similar safety and efficacy to subcutaneous administration of the reference (Epogen, Procrit).
In the study, 320 adult patients at 68 US sites, all of whom had end-stage kidney disease and anemia and were stable on intravenous or subcutaneous epoetin alfa, were randomized 1:1 to receive either the biosimilar or the reference product subcutaneously. Those who were receiving intravenous therapy were started at a dose of 20% to 30% lower than those who had been receiving the subcutaneous drug and were treated for 12 to 18 weeks in the titration phase.
The 246 patients who demonstrated stable subcutaneous dosing were rerandomized to receive subcutaneous biosimilar (n = 124) or reference epoetin alfa (n = 122) 1 to 3 times per week in a 16-week maintenance phase. Coprimary end points were least squares (LS) mean difference between treatments in mean weekly hemoglobin concentration and mean weekly epoetin dose per kilogram body weight during the last 4 weeks of treatment in the maintenance phase.
For the primary analysis conducted among the intent-to-treat population, the LS mean difference (95% CI) between treatment groups in mean weekly hemoglobin levels during the last 4 weeks of treatment was 0.04 g/dL (−0.17 to 0.24 g/dL) and the difference in mean weekly epoetin dose per kg of body weight was −2.34 U/kg per week (−14.51 to 9.82 U/kg per week).
The 95% CIs were contained within the prespecified equivalence margins of ±0.5 g/dL for weekly hemoglobin and ±45 U/kg per week for weekly epoetin dose per kg of body weight.
For the safety population in the titration phase, 59.6% of patients in both the biosimilar and reference groups reported at least 1 adverse event (AE), with headache representing the most commonly reported AE. There were 4 and 6 AEs leading to study discontinuation in the biosimilar and reference groups, respectively. In the maintenance phase, approximately 70% of patients in each group reported at least 1 AE, with nausea being the most commonly reported.
Three patients receiving the biosimilar and 2 receiving the reference died during the maintenance phase. The patients’ deaths were all considered not related or probably not related to the study drug.
In total, 2 patients in the biosimilar arm and 3 patients in the reference arm tested positive for antidrug antibodies, and 1 patient in each group tested positive at baseline before the first dose of study drug in the maintenance phase. No patients had neutralizing antibodies.
According to the authors, this clinical trial demonstrated the equivalent efficacy and similar safety of subcutaneous Retacrit versus the reference product and support the opportunity to provide patients with equivalent therapy at a potentially reduced cost.
Fishbane S, Spinowitz BS, Wisemandle WA, Martin NE. Randomized controlled trial of subcutaneous epoetin alfa-epbx versus epoetin alfa in end-stage kidney disease. Kidney Int Rep. 2019;4(9):1235-1247. doi: 10.1016/j.ekir.2019.05.010.