Randomized Controlled Trial of Subcutaneous Epoetin Alfa-epbx Versus Epoetin Alfa in End-Stage Kidney Disease

© 2019 Introduction: This double-blind, randomized controlled trial compared the safety and efficacy of subcutaneous epoetin alfa-epbx, an epoetin alfa biosimilar, with the reference product, epoetin alfa, in hemodialysis patients with end-stage kidney disease (ESKD) and anemia who were receiving epoetin alfa maintenance treatment. Methods: Eligible patients (n = 320) were randomized (1:1) to subcutaneous epoetin alfa-epbx or epoetin alfa in a titration phase; patients who demonstrated stable subcutaneous dosing (n = 246) were re-randomized to receive subcutaneous epoetin alfa-epbx or epoetin alfa 1 to 3 times per week in a 16-week maintenance phase. Co-primary endpoints were least-squares mean difference between treatments in mean weekly hemoglobin concentration and mean weekly epoetin dose per kilogram body weight (BW) during the last 4 weeks of treatment in the maintenance phase. Results: The least-squares mean difference (95% confidence interval [CI]) between treatments in weekly hemoglobin was 0.04 g/dl (−0.17 to 0.24 g/dl) and weekly epoetin dose/kg BW 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 (weekly hemoglobin) and ±45 U/kg per week (weekly epoetin dose/kg BW). In the epoetin alfa-epbx and epoetin alfa groups, respectively, 4.0% and 4.1% of patients required blood transfusions, 69.7% and 70.5% reported adverse events, 18.9% and 27.0% reported serious adverse events, and 3 and 2 deaths were reported. Five patients were confirmed positive for anti-recombinant human erythropoietin antibody, 2 of whom tested positive at baseline. All patients tested negative for neutralizing antibodies. Conclusions: This comparative clinical trial demonstrated equivalence in efficacy and similar safety of subcutaneously administered epoetin alfa-epbx to epoetin alfa

Steady-State Pharmacokinetics of Micafungin and Voriconazole after Separate and Concomitant Dosing in Healthy Adults

We assessed the pharmacokinetics and interactions of steady-state micafungin (Mycamine) or placebo with steady-state voriconazole in 35 volunteers. The 90% confidence intervals around the least-squares mean ratios for micafungin pharmacokinetic parameters and placebo-corrected voriconazole pharmacokinetic parameters were within the 80%-to-125% limits, indicating an absence of drug interaction

Intravenous epoetin Alfa-epbx versus epoetin alfa for treatment of anemia in end-stage kidney disease

© 2018 by the American Society of Nephrology. Background and objectives This study was conducted to compare the safety and efficacy of intravenous epoetin alfa-epbx, an epoetin alfa biosimilar, to epoetin alfa in patients on hemodialysis with ESKD and anemia. Design, setting, participants, & measurements In this 24-week, multicenter, double-blind comparative efficacy and safety study, 612 patients on hemodialysis with ESKD and anemia who had stable hemoglobin and were receiving stable doses of intravenous epoetin alfa were randomized (1:1) to intravenous epoetin alfa or epoetin alfa-epbx. Dosing was adjusted according to the epoetin alfa prescribing information. The coprimary efficacy endpoints were the least squares mean difference between the two treatments in mean weekly hemoglobin level and mean weekly epoetin dose per kilogram of body weight during the last 4 weeks of treatment. Results The least squares mean difference between epoetin alfa-epbx and epoetin alfa in weekly hemoglobin was –0.12 g/dl and the 95% confidence interval (–0.25 to 0.01) was contained within the prespecified equivalence margin (–0.5 to 0.5 g/dl). The least squares mean difference between epoetin alfa-epbx and epoetin alfa in weekly epoetin dose per kilogram of body weight was 0.37 U/kg per week, and the 95% confidence interval (–10.40 to 11.13) was contained within the prespecified equivalence margin (–45 to 45 U/kg per week). Incidences of adverse events (77.1% versus 75.3%), serious adverse events (24.9% versus 27.0%), and deaths (n=5 versus 6) were similar between the epoetin alfa-epbx and epoetin alfa groups, respectively. Five patients tested positive for anti-recombinant human erythropoietin antibodies at baseline, and two additional patients (n=1 per group) developed anti-recombinant human erythropoietin antibodies while on study treatment. All patients tested negative for neutralizing antibodies, and no patient in either group experienced an event of pure red cell aplasia. Conclusions This 24-week, comparative, clinical trial in patients on hemodialysis with ESKD and anemia demonstrated there is no clinically meaningful difference in efficacy or safety between epoetin alfa-epbx and epoetin alfa