title: Safety, immunogenicity and efficacy of subcutaneous biosimilar epoetin-α (HX575) in non-dialysis patients with renal anemia: a multi-center, randomized, double-blind study.
abstract: BACKGROUND
  HX575 is a biosimilar version of epoetin-α that is approved for the treatment of anemia associated with chronic kidney disease (CKD) using the intravenous route of administration. Here we report data from a study of anemic pre-dialysis patients to assess the safety, immunogenicity and efficacy of subcutaneous (s.c.) administration of HX575 vs. Erypo®/Eprex® (Ortho Biotech, Neuss, Germany).
  
  
  METHODS
  This was a randomized, double-blind study in adult patients (n = 337) with Stage III - V CKD and a hemoglobin (Hb) level of 7.5 - 11.0 g/dl. Eligible patients were randomized to 52 weeks of treatment with HX575 or Erypo®/Eprex® at a starting dose of 25 IU/kg body weight 3 times weekly or 75 IU/kg body weight once weekly during Weeks 1 - 5. This could be adjusted after 5 weeks to maintain Hb levels between 10 and 12 g/dl. The primary objective was to assess the safety and immunogenicity of HX575 compared with Erypo®/Eprex®. Efficacy endpoints were mean absolute change in Hb from baseline to end of Week 13 and mean weekly epoetin dosage in Weeks 11 - 13.
  
  
  RESULTS
  HX575 was equivalent to Erypo®/Eprex® in terms of maintaining Hb levels and epoetin dose requirements. Two patients in the HX575 group developed neutralizing antibodies (NAbs) to erythropoietin, which resulted in the study being terminated prematurely. Aside from these two events, reported adverse events were as expected for patients with Stage III - V CKD and similar in both treatment groups.
  
  
  CONCLUSIONS
  This study demonstrated the efficacy and therapeutic equivalence of s.c. HX575 compared with the reference epoetin-α, but 2 patients developed NAbs during treatment with s.c. HX575 in this study. Results of a thorough root-cause analysis reported elsewhere indicate that increased tungsten exposure in pre-filled syringes precipitated immunogenic reactions.
authors.affiliation: Department of Nephrology and Hypertension, University of Erlangen-Nürnberg, Erlangen,Germany.
authors.forename: Marianne
authors.initials: M
authors.lastname: Haag-Weber
authors.forename: Kai-Uwe
authors.initials: KU
authors.lastname: Eckardt
authors.forename: Walter H
authors.initials: WH
authors.lastname: Hörl
authors.forename: Simon D
authors.initials: SD
authors.lastname: Roger
authors.forename: Andrea
authors.initials: A
authors.lastname: Vetter
authors.forename: Karsten
authors.initials: K
authors.lastname: Roth
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D000906:Antibodies / Q000276:immunology*; D004311:Double-Blind Method; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D006397:Hematinics / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D051436:Renal Insufficiency, Chronic / Q000150:complications*; D055815:Young Adult
chemical_list: D000906:Antibodies; D006397:Hematinics; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa