Binocrit (epoetin alfa biosimilar) / Medice, Rentschler, Sandoz - LARVOL DELTA

Management of chemotherapy‐induced anemia (CIA) with biosimilar epoetin alfa (Binocrit) in patients with colorectal cancer (CC): An interim analysis of an ongoing French national observational study (The OncoBOS study) (ASCO-GI 2015) - Abstract #742; P=Obs; N=96; “The mean increase in Hb level was 1.2 g/dL after 1 month and 1.7 g/dL after 3 months (p<0.001 vs. BL) of Binocrit treatment. A Hb increase ≥1 g/dL was achieved by 56.8% of patients at week 3-4 and 77.6% at week 12; a Hb increase ≥2 g/dL was achieved by 17.9% and 47.4% of patients at the same time points. Patients received a median dose of 30,000 IU Binocrit once weekly. Four of the 96 patients (4.2%) required a dose increase.”

Observational data • Biosimilar

Management of chemotherapy‐induced anemia (CIA) with biosimilar epoetin alfa (Binocrit) in patients with pancreatic cancer (PC): An interim analysis of an ongoing French national observational study (The OncoBOS study) (ASCO-GI 2015) - Abstract #479; P=Obs, N=59; “The mean increase in Hb level was 1.1 g/dL after 1 month and 1.2 g/dL after 3 months (p<0.001 vs BL) of Binocrit treatment. A Hb increase ≥1 g/dL was achieved by 48.3% of patients at week 3-4 and 54.2% at week 12; a Hb increase ≥2 g/dL was achieved by 25.9% and 35.4% of patients at the same time points. Patients received a median dose of 30,000 IU Binocrit once weekly. Three of the 59 patients (5.1%) required a dose increase.”

Observational data • Biosimilar

Long-Term Real-World Post-approval Safety Data of Multiple Biosimilars from One Marketing-Authorization Holder After More than 18 Years Since Their First Biosimilar Launch. (PubMed, Drug Saf) - "This is one of the largest reviews of post-approval biosimilar pharmacovigilance data to date by one MAH. The real-world experience of all eight marketed Sandoz biosimilars for up to 18 years demonstrates that Sandoz biosimilars can be used as safely as their respective reference biologics. Therefore, patients and healthcare providers can be confident in the clinical benefit and safety of Sandoz biosimilars. It is reasonable to believe that similar conclusions about safety may be reached for other biosimilars developed and approved to the high standards as are already in place by major health authorities such as the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). The long-term safety of biosimilars demonstrated here provides strong support for the concept of biosimilarity."

Biosimilar launch • Journal • Real-world • Real-world evidence

ELEMENT-MDS: A Study to Compare the Efficacy and Safety of Luspatercept in Participants With Myelodysplastic Syndrome (MDS) and Anemia Not Receiving Blood Transfusions (clinicaltrials.gov) - P3 | N=360 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open • Anemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Patient Blood Management in Microsurgical Procedures for Reconstructive Surgery. (PubMed, Diagnostics (Basel)) - " A collaboration between the two departments (Department of Transfusion Medicine and Department of Reconstructive Surgery) resulted in the application of a therapeutic protocol with erythropoietic stimulating agents (ESAs) (Binocrit 6000 UI/week) and intravenous iron every other day, starting the second day after surgery... Preliminary data from our protocol show an optimal therapeutic response, notwithstanding the very limited scientific literature and data available in this specific surgical field. The enrollment of further patients will allow us to validate this therapeutic protocol with statistically sound data."

Journal • Surgery • Hematological Disorders • Infectious Disease • Inflammation • Thermal Injury

ELEMENT-MDS: A Study to Compare the Efficacy and Safety of Luspatercept in Participants With Myelodysplastic Syndrome (MDS) and Anemia Not Receiving Blood Transfusions (clinicaltrials.gov) - P3 | N=360 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

New P3 trial • Anemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Epoetin alfa biosimilar (HX575): a review of 15 years' post-approval clinical experience. (PubMed, Crit Rev Oncol Hematol) - "This review will outline the safety results collected from key studies that have added to the extensive HX575 (Binocrit® unless otherwise stated) clinical experience. With a focus on all approved indications, we will review the safety data collected across a range of study types, to further consolidate the reassurance for the use of HX575 in these indications."

Journal • Review • Chronic Kidney Disease • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Nephrology • Renal Disease

EPO-TRAUMA: ErythroPOietin Alfa to Prevent Mortality and Reduce Severe Disability in Critically Ill TRAUMA Patients (clinicaltrials.gov) - P3 | N=2500 | Recruiting | Sponsor: Australian and New Zealand Intensive Care Research Centre | Trial completion date: Mar 2025 ➔ Dec 2025 | Trial primary completion date: Mar 2025 ➔ Dec 2025

Trial completion date • Trial primary completion date • CNS Disorders • Mood Disorders • Vascular Neurology

Glycan analysis of erythropoiesis-stimulating agents. (PubMed, J Pharm Biomed Anal) - "In this study, a combination of chromatography and mass spectrometry analysis has been used to characterise and compare the glycosylation profiles of five ESA products; Eprex® (epoetin alfa), NeoRecormon® (epoetin beta), Binocrit® (epoetin alfa biosimilar), Silapo (epoetin alfa biosimilar) and Aranesp® (darbepoetin alfa). The products exhibit notable differences in N- and O-glycosylation, including attributes such as sialic acid occupation, O-acetylation, N-acetyllactosamine extended antennae and sulphated/penta-sialylated N-glycans, which have the potential to cause divergence of therapeutic potencies. The study highlights the need for continued monitoring of ESA product glycosylation, ideally allied to pharmacological data, in order to ensure consistency and therapeutic equivalence between products and enhance our understanding of ESA structure-activity-relationships."

Journal • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

EPO-TRAUMA: ErythroPOietin Alfa to Prevent Mortality and Reduce Severe Disability in Critically Ill TRAUMA Patients (clinicaltrials.gov) - P3; N=2500; Recruiting; Sponsor: Australian and New Zealand Intensive Care Research Centre; Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Mood Disorders • Vascular Neurology

EPO-TRAUMA: ErythroPOietin Alfa to Prevent Mortality and Reduce Severe Disability in Critically Ill TRAUMA Patients (clinicaltrials.gov) - P3; N=2500; Not yet recruiting; Sponsor: Australian and New Zealand Intensive Care Research Centre

Clinical • New P3 trial • CNS Disorders • Mood Disorders • Vascular Neurology

Epoetin alfa Hexal: breakdown product out of specification [Google translation] (Apotheke Adhoc) - "Hexal recalls individual batches of Epoetin alfa Hexal. As part of the ongoing stability program, specification deviations for a known degradation product of the active ingredient were identified. Patient safety is not at risk."

Commercial • Anemia

Epoetin alfa for the treatment of myelodysplastic syndrome-related anemia: A review of clinical data, clinical guidelines, and treatment protocols. (PubMed, Leuk Res) - "The effectiveness of biosimilar epoetin alfa (Binocrit, Sandoz) to correct anemia in lower-risk MDS patients has also been demonstrated in a retrospective, single-center, observational study. The recent approval of epoetin alfa by the EMA in this setting will provide clinicians with a welcome, approved treatment option for lower-risk MDS."

Clinical data • Clinical guideline • Journal • Review • Anemia • Fatigue • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

HX575 epoetin alfa subcutaneously (S.C.) in chronic kidney disease (CKD) (SENSE) (clinicaltrials.gov) - P3, N=360; Sponsor: Sandoz; Recruiting -> Active, not recruiting.

Enrollment closed • Biosimilar

Biosimilar epoetin alfa (HX575) for the treatment of chemotherapy-induced anaemia: Development, approval and 10 years’ clinical experience (ESMO 2017) - "...HX575 (Binocrit®, epoetin alfa biosimilar) was approved in Europe in 2007 for the treatment of chemotherapy-induced anaemia (CIA)...As of Feb 2017, HX575 has generated >252,000 patient years’ experience in CIA worldwide. Accumulated data and experience over a decade are reassuring that HX575 is effective and well tolerated for the treatment of CIA in patients with different cancer types."

Observational data • Real-World Evidence • Retrospective data • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Epoetin alfa biosimilar increases hemoglobin levels in anemic patients undergoing chemotherapy for a lymphoid malignancy (HCPLive) - P=NA, N=563; OncoBOS study; "In an abstract presented at the American Society of Hematology Annual Meeting...results from the OncoBOS study,  a prospective non-interventional study of the drug in a routine clinical practice setting...'in real-life clinical conditions, Binocrit increases effectively Hb without any adverse drug reaction in anemic patients with lymphoid malignancies, whatever chemotherapy [they] received.'"

Clinical data • Biosimilar

Binocrit: Anticipated regulatory filing in US for anemia in 2017 (Novartis) - Q4 FY 2016 Results

Anticipated BLA • Biosimilar

A comparison of the safety and efficacy of HX575 (epoetin alfa proposed biosimilar) with epoetin alfa in patients with end-stage renal disease (Am J Nephrol) - P3, N=435; NCT01693029; Sponsor: Sandoz; "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."

P3 data • Biosimilar

Sandoz receives EC approval for subcutaneous route of administration in biosimilar Binocrit's nephrology indication (Novartis Press Release) - "Sandoz...announced today that the European Commission (EC) has approved a type II variation for the addition of a subcutaneous (s.c.) route of administration in Binocrit's (epoetin alfa) nephrology indication...The EU approval was based on data from the SENSE clinical study...to evaluate the safety and immunogenicity of HX575 epoetin alfa in the treatment of anemia associated with chronic kidney disease in pre-dialysis and dialysis patients."

European regulatory • Biosimilar

Real-world evidence shows switching among ESAs in CKD is not associated with risks to safety, efficacy (Center for Biosimilars) - P=NA, N=14,400; "Overall, the investigators say lack of efficacy or safety issues occurred in 7.7% and 4.5%, respectively, of patients in the reference group. In the biosimilar group, the corresponding percentages of patients were 7.8% and 4.0%."

Clinical data

Binocrit (EMEA) - "...the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending a change to the terms of the marketing authorisation for the medicinal product Binocrit....Binocrit is indicated for the treatment of symptomatic anaemia (haemoglobin concentration of≤ 10 g/dl) in adults with low- or intermediate-1-risk primary myelodysplastic syndromes (MDS) who have low serum erythropoietin (< 200 mU/ml)."

European regulatory

NO DIFFERENCES IN HEMOGLOBIN LEVELS OR CLINICAL OUTCOMES DURING THE SWITCH TO BIOSIMILAR ERYTHROPOIETIN IN LOWER-RISK MYELODYSPLASTIC SYNDROMES (MDS 2019) - "...We analyzed hemoglobin (Hb) levels during the switch Darbepoetin alfa (Aranesp®) to biosimilar Epoetin alfa (Binocrit®).From January to September of 2018, in our hospital we have initiated the treatment with biosimilar Epoetin alfa...These patients with lower-risk myelodysplastic syndromes who were under treatment with erythropoiesis-stimulating agents did not have statistically differences in hemoglobin level, clinical relevance nor clinical results with the equivalences and settings proposed with the switch between Darbepoetin alfa to biosimilar Epoetin alfa."

Clinical • Clinical data