Safety, immunogenicity and efficacy of subcutaneous biosimilar epoetin-α (HX575) in non-dialysis patients with renal anemia: a multi-center, randomized, double-blind study

Haag–Weber, Marianne; Eckardt, Kai Uwe; Hörl, Walter H.; Roger, Simon D.; Vetter, Andrea; Roth, Karsten

doi:10.5414/cn107304

Cited by 86 publications

(76 citation statements)

References 18 publications

(19 reference statements)

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“…The product was subcutaneously administered to CKD patients, Detailed analyses found that contamination by tsungsten during the manufacturing of the syringes used for the primary packaging was the most likely cause of protein denaturation and aggregation, which may have led to the occurrence of toxicity in these two patients. 57,58 After the relationships with the drugs were reported, voluntary changes by physicians in prescribing gadodiamide and epoetin alfa and by physicians and parents in changing aspirin use in children resulted in declines in PRCA/NSF and RS reports, respectively. Publication was important, given that several groups were investigating causal relationships at the same time.…”

Section: Discussionmentioning

confidence: 99%

Linking Drugs to Obscure Illnesses: Lessons from Pure Red Cell Aplasia, Nephrogenic Systemic Fibrosis, and Reye’s Syndrome. A Report From the Southern Network on Adverse Reactions (SONAR)

et al. 2012

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Identification of serious adverse drug reactions (sADRS) associated with commonly used drugs can elude detection for years. Reye’s syndrome (RS), nephrogenic systemic fibrosis (NSF), and pure red cell aplasia (PRCA) among chronic kidney disease (CKD) patients were recognized in 1951, 2000, and 1998, respectively. Reports associating these syndromes with aspirin, gadodiamide, and epoetin, were published 29, 6, and 4 years later, respectively. We obtained primary information from clinicians who identified causes of these sADRs and reviewed factors contributing to delayed identification of these toxicities. Overall, 3,500 aspirin-associated RS cases in the United States, 1,605 gadolinium-associated NSF cases, and 181 epoetin-associated PRCA cases were reported. Delays in FDA regulation of over-the- counter medications and administration of aspirin to children contributed to development of RS. For NSF, in 1996, the Danish Medicine Agency approved high-dose gadodiamide administration to chronic kidney disease (CKD) patients undergoing MR scans. Overall, 88 % of Danish NSF cases were from two hospitals and 97 % of United States’ NSF cases were from 60 hospitals. These hospitals frequently administered high-doses of gadodiamide to CKD patients. Another factor was the decision to administer linear chelated contrast agents versus lower risk macrocyclic chelated agents. For PRCA, increased use of subcutaneous epoetin formulations to CKD patients, in part due to convenience and cost-savings considerations, and a European regulatory requirement requiring removal of albumin as a stabilizer, led to toxicity. Overall, 81, 13, and 17 years elapsed between drug introduction into practice and identification of a causal relationship for aspirin, erythropoietin, and gadodiamide, respectively. A substantial decline in new cases of these sADRs occurred within two years of identification of the offending drug. Clinicians should be vigilant for sADRs, even for frequently-prescribed pharmaceuticals, particularly in settings where formulation or regulatory changes have occurred, or when over-the-counter, off-label, or pediatric use is common

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Section: Discussionmentioning

confidence: 99%

Linking Drugs to Obscure Illnesses: Lessons from Pure Red Cell Aplasia, Nephrogenic Systemic Fibrosis, and Reye’s Syndrome. A Report From the Southern Network on Adverse Reactions (SONAR)

et al. 2012

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“…With the exception of a report on unexpected immunogenicity of the biosimilar erythropoietin alpha HX575 [9], these products seem to be of equal or perhaps better quality compared with the originator products [10].…”

Section: Introductionmentioning

confidence: 94%

Immunogenicity of biosimilar monoclonal antibodies

Brinks¹

2013

GaBI J

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Biosimilar monoclonal antibodies (mAbs) are making their way onto the drug market. Because these are complex molecules in terms of structure and function, assessing similarity between originator and biosimilar mAb is challenging. This review discusses the hallmarks of similarity testing between originator products and mAb biosimilars in terms of product quality attributes, non-clinical and clinical studies, with a focus on immunogenicity. Sparse data on immunogenicity of biosimilar mAb products is given.

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“…18 In addition, one article presented the findings of a trial in 337 renal anemia patients not yet receiving renal replacement therapy (INJ-17), 19 another summarized the findings of a retrospective clinical audit of 152 patients in the oncology setting (for convenience, hereafter RCA), 20 while another reported the results of a post-approval EMA-mandated safety commitment study (EPO-PASS). 21 One paper described the background and methodology of a pharmaco-epidemiological study of HX575 in the hemodialysis setting that is still in the recruitment phase (MONITOR-CKD5).…”

Section: Clinical Studies Overviewmentioning

confidence: 99%

“…Additional safety data are summarized in the study's publication. 19 Study RCA: Patients with chronic kidney disease not receiving dialysis…”

Section: Safetymentioning

confidence: 99%

“…Additional safety data have been summarized elsewhere. 4,6 Study INJ-17: patients with chronic kidney disease not receiving dialysis 19 Methods Study INJ-17 was designed to evaluate the safety and immunogenicity of HX575 relative to Eprex/Erypo during long-term SC administration in patients with chronic kidney disease (CKD) stages 3 through 5 not yet on dialysis. This study was conducted because the SC license for Eprex/Erypo had been withdrawn following a rise in the incidence of PRCA in many patients treated with this agent; hence, studies such as INJ-9 and INJ-11 could not evaluate SC regimens.…”

Section: Safetymentioning

confidence: 99%

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Clinical efficacy and safety of HX575, a biosimilar recombinant human erythropoietin, in the management of anemia

Abraham¹,

MacDonald²

2012

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Abstract:Since the expiration of the patent for epoetin alfa in Europe in 2004, the European Medicines Agency has approved three biosimilar erythropoietins. Using the European Medicines Agency's European Public Assessment Reports and scientific publications, we review the evidence regarding the clinical efficacy and safety of HX575 (Sandoz/Novartis) relative to the originator product Eprex/Erypo (Johnson & Johnson). Clinical efficacy is assessed as a function of therapeutic equivalence of a biosimilar and originator product, while safety is evaluated in terms of immunogenicity, venous thromboembolism, and mortality. Five studies that examined chronic renal failure and oncology populations are reviewed. In the renal setting, these studies include a randomized controlled trial on Hb maintenance in patients receiving long-term hemodialysis, a randomized safety trial in patients with chronic kidney disease not yet requiring renal replacement therapy, and a post-approval saftey commitment study. Studies in the cancer setting include a clinical validation study in patients with solid tumors receiving antineoplastic chemotherapy and a retrospective clinical audit of Binocrit in routine clinical practice. Based on available therapeutic equivalence and safety data, the clinical and safety outcomes of treatment with HX575 are likely to be similar to those of the originator product Eprex/Erypo. Both products can be considered interchangeable in the management of anemia in the approved indications, and patients transferred from the reference product to the biosimilar product are expected to show the same efficacy and safety outcomes. There is no evidence of the interchangeability of HX575 with other biosimilar or originator erythropoietins other than Eprex/Erypo. In keeping with European Medicines Agency guidance about traceability, it is recommended that clinicians document the product prescribed by its commercial name, especially when switching patients from an originator to a biosimilar or vice versa.

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Safety, immunogenicity and efficacy of subcutaneous biosimilar epoetin-α (HX575) in non-dialysis patients with renal anemia: a multi-center, randomized, double-blind study

Cited by 86 publications

References 18 publications

Linking Drugs to Obscure Illnesses: Lessons from Pure Red Cell Aplasia, Nephrogenic Systemic Fibrosis, and Reye’s Syndrome. A Report From the Southern Network on Adverse Reactions (SONAR)

Linking Drugs to Obscure Illnesses: Lessons from Pure Red Cell Aplasia, Nephrogenic Systemic Fibrosis, and Reye’s Syndrome. A Report From the Southern Network on Adverse Reactions (SONAR)

Immunogenicity of biosimilar monoclonal antibodies

Clinical efficacy and safety of HX575, a biosimilar recombinant human erythropoietin, in the management of anemia

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