Matthew R Weir1, Pablo E Pergola2, Rajiv Agarwal3, Jeffrey C Fink1, Nelson P Kopyt4, Ajay K Singh5, Jayant Kumar6, Susanne Schmitt7, Gregor Schaffar7, Anita Rudy7, Jim P McKay8, Radmila Kanceva7. 1. Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA. 2. Renal Associates PA and UT Health, San Antonio, Texas, USA. 3. Indiana University School of Medicine, Indianapolis, Indiana, USA. 4. Lehigh Valley Hospital, Allentown, Pennsylvania, USA. 5. Harvard Medical School, Boston, Massachusetts, USA. 6. Renal Medicine Associates, Albuquerque, New Mexico, USA. 7. Hexal AG, Holzkirchen, Germany. 8. Sandoz Inc., Princeton, New Jersey, USA.
Abstract
BACKGROUND:HX575 (biosimilar epoetin alfa) was approved in Europe in 2007 for the treatment of chronic kidney disease (CKD)-related anemia. This study assessed the clinical equivalence of HX575 with the US-licensed reference epoetin alfa (Epogen®/Procrit®, Amgen/Janssen) following subcutaneous (SC) administration in dialysis patients with CKD-related anemia. METHODS: This randomized, double-blind, parallel-group, multicenter study (NCT01693029) was conducted at 49 US clinical sites. Eligible patients were aged ≥18 years, had end-stage renal disease, were on hemodialysis or peritoneal dialysis for ≥6 months (or ≥12 months in the case of a failed kidney transplant), and were receiving treatment with stable SC doses of epoetin alfa. Eligible patients also had mean hemoglobin (Hb) concentration between 9.0 and 11.5 g/dL during the screening period. The primary endpoint was the mean absolute change in Hb concentration between the screening/baseline period (week-4 to week-1) and the evaluation period (weeks 21 to 28). RESULTS: Hb values at the end of the evaluation period and the Hb change from baseline to evaluation period were similar between treatment groups. The estimated difference between groups in mean absolute change in Hb concentration was -0.093 g/dL, with 90% CI (-0.23 to 0.04) entirely within the pre-specified equivalence limits (-0.5 to 0.5 g/dL). The safety profile of each medicine was similar and as expected in dialysis patients, and neither method of treatment led to the development of neutralizing, clinically relevant antibodies. CONCLUSIONS:SC HX575 in dialysis patients with renal anemia was therapeutically equivalent to the reference medicine in terms of maintaining stable Hb levels and safety.
RCT Entities:
BACKGROUND: HX575 (biosimilar epoetin alfa) was approved in Europe in 2007 for the treatment of chronic kidney disease (CKD)-related anemia. This study assessed the clinical equivalence of HX575 with the US-licensed reference epoetin alfa (Epogen®/Procrit®, Amgen/Janssen) following subcutaneous (SC) administration in dialysis patients with CKD-related anemia. METHODS: This randomized, double-blind, parallel-group, multicenter study (NCT01693029) was conducted at 49 US clinical sites. Eligible patients were aged ≥18 years, had end-stage renal disease, were on hemodialysis or peritoneal dialysis for ≥6 months (or ≥12 months in the case of a failed kidney transplant), and were receiving treatment with stable SC doses of epoetin alfa. Eligible patients also had mean hemoglobin (Hb) concentration between 9.0 and 11.5 g/dL during the screening period. The primary endpoint was the mean absolute change in Hb concentration between the screening/baseline period (week-4 to week-1) and the evaluation period (weeks 21 to 28). RESULTS: Hb values at the end of the evaluation period and the Hb change from baseline to evaluation period were similar between treatment groups. The estimated difference between groups in mean absolute change in Hb concentration was -0.093 g/dL, with 90% CI (-0.23 to 0.04) entirely within the pre-specified equivalence limits (-0.5 to 0.5 g/dL). The safety profile of each medicine was similar and as expected in dialysis patients, and neither method of treatment led to the development of neutralizing, clinically relevant antibodies. CONCLUSIONS: SC HX575 in dialysis patients with renal anemia was therapeutically equivalent to the reference medicine in terms of maintaining stable Hb levels and safety.
Authors: Frank Dellanna; David Goldsmith; Andriy Krendyukov; Andreas Seidl; Nadja Höbel; Christian Combe Journal: Drug Des Devel Ther Date: 2017-12-18 Impact factor: 4.162
Authors: Jay B Wish; Marcelo G Rocha; Nancy E Martin; Christian Russel D Reyes; Steven Fishbane; Mark T Smith; George Nassar Journal: Kidney Med Date: 2019-08-28