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

ABSTRACT: 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.

SUBMITTER: Patsialas S

PROVIDER: S-EPMC10112001 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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

Patsialas Stavros S Fowler Heather H Guilatco Ruffy R Salts Stephanie S Xia Feng Richard FR Gomez Perez Sonja S Iwanowitsch Andreas A Kohnle Matthias M

Clinical nephrology 20230501 5

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 Silap ...[more]

PMID: 36871229

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Project description:Background and objectivesThis 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, & measurementsIn 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 end points 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.ResultsThe 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.ConclusionsThis 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.

Project description:Rationale & objectiveEpoetin alfa-epbx is a biosimilar to the reference product, epoetin alfa. We compare the safety of epoetin alfa-epbx versus epoetin alfa based on a pooled analysis of findings from 2 randomized, double-blind, comparative clinical studies, and report new data for the long-term safety of epoetin alfa-epbx.Study designPooled analyses of previously conducted studies.Setting & participantsHemodialysis patients with anemia.InterventionsData from patients who received 1 or more subcutaneous or intravenous doses of study drug were integrated across route of administration in combined randomized groups (epoetin alfa-epbx, n = 423; epoetin alfa, n = 426). Data from patients who received 1 or more doses of epoetin alfa-epbx in either open-label extension trial were integrated across route of administration in a combined long-term safety studies group (n = 576).OutcomesAdverse events (AEs), immunogenicity, and other outcomes were assessed.ResultsIncidences of treatment-emergent AEs, serious AEs, and discontinuation of study drug treatment because of treatment-emergent AEs were similar between combined randomized epoetin alfa-epbx and epoetin alfa, which had mean treatment durations of 18.1 and 17.7 weeks, respectively. Incidences of treatment-emergent AEs, serious AEs, and discontinuation of study drug treatment because of treatment-emergent AEs were 86.5%, 39.4%, and 6.6%, respectively, for the combined long-term safety studies group, which had a mean treatment duration of 40.0 weeks. In total, 12 patients across the combined randomized groups (epoetin alfa-epbx, n = 5; epoetin alfa, n = 7) and 9 patients in the combined long-term safety studies group tested anti-recombinant human erythropoietin antibody positive in 1 or more visits during study conduct. No patient in any group developed neutralizing antibodies or pure red blood cell aplasia.LimitationsEpoetin alfa comparator not included in the long-term safety studies, greater cumulative exposure to study drug for epoetin alfa-epbx, shorter follow-up in the randomized studies, and potential for selection bias among patients in the open-label long-term safety studies.ConclusionsThis analysis reinforces previous conclusions of similar safety profiles between epoetin alfa-epbx and epoetin alfa. Furthermore, epoetin alfa-epbx had no unexpected safety signals during long-term treatment.FundingThis study was funded by Hospira Inc, which was acquired by Pfizer Inc in September 2015.Trial registrationClinicalTrials.gov EPOE-10-13 (NCT01473420); EPOE-10-01 (NCT01473407); EPOE-11-04 (NCT01628120); EPOE-11-03 (NCT01628107).

Dataset Information

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

Publications

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

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