Comparison of two epoetin brands in anemic hemodialysis patients: results of two efficacy trials and a single‐dose pharmacokinetic study

Abstract

Epoetin alpha is recombinant human erythropoietin with established efficacy and safety in the treatment of renal anemia. Epoetin omega is recombinant erythropoietin that differs from epoetin alpha in the sugar moiety. We compared the two epoetins in two 12-week efficacy studies (S1, S2) with twice-weekly dosing, and a single-dose crossover pharmacokinetic (PK) study in severely anemic hemodialysis patients. Epoetins were delivered subcutaneously in all studies. S1 was randomized (omega n = 39, alpha n = 38), while S2 included the patients from S1 (omega n = 32, alpha n = 24) with 'switched' treatments (omegaleft arrow over right arrowalpha). In the intent-to-treat analysis, average weekly difference in hemoglobin vs. the baseline value was higher in omega-treated patients in both studies: 1.94 +/- 0.81 vs. 1.23 +/- 0.62 g/dL in S1 and 1.44 +/- 0.72 vs. 0.95 +/- 0.62 g/dL in S2. The unadjusted and adjusted omega-alpha differences in S1 were 0.71 g/dL (95% CI 0.38-1.04; P < 0.001) and 0.78 g/dL (95% CI 0.49-1.08; P < 0.001), respectively. Differences in S2 were 0.48 g/dL (95% CI 0.11-0.86; P = 0.012) and 0.46 g/dL (95% CI 0.1-0.82; P = 0.025), unadjusted and adjusted, respectively. Average weekly epoetin dose was lower in the omega groups in both studies: 87 +/- 25 vs. 108 +/- 21 IU/kg in S1 and 106 +/- 25 vs. 125 +/- 20 IU/kg in S2. The unadjusted and adjusted omega-alpha differences in S1 were -21 IU/kg (95% CI -32 to -11; P < 0.001) and -24 IU/kg (95% CI -35 to -13; P < 0.001), respectively. Differences in S2 were -19 IU/kg (95% CI -31 to -6; P = 0.006) and -15 IU/kg (95% CI -28 to -2; P = 0.04), unadjusted and adjusted, respectively. In the PK study (n = 17), the peak and total exposure to epoetin after 50 IU/kg of either drug was approximately twice greater for epoetin omega: C(max) omega/alpha 2.19 (95% CI 1.55-3.11), AUC omega/alpha 2.24 (95% CI 1.64-3.06). Epoetins were comparably well tolerated. In hemodialysis patients, subcutaneous epoetin omega apparently provides greater bioavailability and anti-anemic effect per administered dose (IU) than epoetin alpha.

Comparative effectiveness and safety of erythropoiesis-stimulating agents (biosimilars vs originators) in clinical practice: a population-based cohort study in Italy

“…Similar results were obtained from the meta-analysis of seven studies with a sample of 2220 patients comparing epoetin α originator with biosimilar on all-cause mortality (OR 1.04, 0.53 to 2.01) 2425 27–31 Risk estimates on MACE come from only one study (462 patients) comparing epoetin α originator versus biosimilars and was inconclusive (OR 0.49, 0.17 to 1.47) 24…”

Emerging erythropoiesis-stimulating agents

“…52 Although only a small number of patients with CKD treated with epoetin omega have been evaluated within long-term controlled trials, the experience to date suggests that epoetin omega is as effective in correcting anemia as epoetin alfa and epoetin beta. [53][54][55] recombinant human erythropoietin isoforms with a greater number of sialic residues have longer half-lives and greater biological activity in vivo than those with fewer resi dues. 56 Most sialic acid residues are attached to the three N-linked glycosylation chains; thus, site-directed mutagenesis targeting amino acids not involved in erythropoietin receptor binding has been used to synthesize analogues with increased amounts of sialic acid.…”