Encicarb (ferric carboxymaltose) / Emcure - LARVOL DELTA

Hypophosphatemia after High Dosage Iron Substitution with Ferric Carboxymaltose (FCM) and Iron Isomaltoside (IM) – the Randomised Controlled Home Afers 1 Trial (ASH 2018) - "No severe adverse events occurred in either group. In conclusion, while both FCM and IM provide efficient iron substitution in iron deficiency anaemia, FCM induced a substantially higher incidence of hypophosphatemia."

Clinical • Biosimilar • Hematological Disorders • Renal Disease

Randomized, Double-Blind Trial of Ferumoxytol Compared to Ferric Carboxymaltose for Treatment of Iron Deficiency Anemia: Safety and Efficacy (ASH 2017) - P3; "While there is little debate as to the efficacy of IV irons on increasing hemoglobin concentrations in patients with IDA, the occurrence of rare but potentially serious acute HSRs continues to be a focus of concern. Very few well conducted trials have compared two or more IV iron formulations by evaluating HSR and hypotension as primary endpoints. In this study there was no significant difference between FCM and ferumoxytol in the composite endpoints of moderate to severe HSR, including anaphylaxis, or moderate to severe hypotension, serious cardiovascular events or all-cause mortality."

Clinical • Biosimilar • Chronic Kidney Disease • Hematological Malignancies • Immunology

Prospsective phase II pilot study to evaluate the use of intravenous iron in the treatment of anemia in cancer patients. (ASCO 2018) - P2; "...Patients received Ferinject (ferric carboxymaltose) 1000mg injection on the first day of chemotherapy... IV iron supplementation alone showed promising result in improving anemia in cancer patients. Hepcidin may predict response to IV iron in cancer and chemotherapy induced anemia, and is superior to TSAT or ferritin for this purpose."

Clinical • P2 data • Oncology

Reducing the rate of acute adverse reactions during rapid intravenous infusion of iron in pregnancy - a prospective comparative audit of Iron Carboxymaltose and Iron Polymaltose at Auckland City Hospital, New Zealand (HAA 2016) - "Treatment for IDA using intravenous (IV) Iron ferric carboxymaltose (IFC) via a rapid infusion delivers a higher concentration at a greater rate compared with a rapid infusion protocol of iron polymaltose (IP). Conclusions IFC in pregnancy in our institution has a reduced side effect profile and provides a more time efficient way of administering iron in pregnancy and IV iron can be available to more women with no increase in staff resources. We have now adopted IFC as the standard iron formulation in pregnancy."

Clinical • Biosimilar • Hematological Malignancies • Oncology

Open-label study of the efficacy and safety of intravenous ferric carboxymaltose in pregnant women with restless legs syndrome. (PubMed) - "These data provide promising evidence on the safety and efficacy of FCM for moderate-to-severe RLS in pregnant women with iron deficiency or anemia. Therefore, a future placebo-controlled study is warranted."

Journal • Biosimilar

A fast-track anaemia clinic in the Emergency Department: feasibility and efficacy of intravenous iron administration for treating sub-acute iron deficiency anaemia. (PubMed) - Blood Transfus - "Our data support the feasibility of a clinical protocol for management of sub-acute anaemia with IV iron in the ED. IV iron was efficacious, safe and well tolerated. Early management of anaemia will improve the use of blood products in the ED."

Journal • Biosimilar • Complement-mediated Rare Disorders

Iron Deficiency Increases Platelet Procoagulant Capacity in a Ferric Chloride Model of Arterial Thrombosis (ISTH-SSC 2018) - "...Resultant alterations in thrombotic tendency have not been extensively studied.Aims: To evaluate thrombotic tendency in a rat model of iron deficiency. Sprague-Dawley rats were fed control (Con, 196mg iron/kg) or iron deficient chow (Def, < 10mg iron/kg) for 7 weeks and additionally received 3 doses of either 20mg ferric carboxymaltose/kg BW i.p. (Def+Fe) or placebo (Pl)... ID leads to thrombocytosis with increased procoagulant capacity. In this model of ferric chloride-induced arterial thrombosis, ID is associated with increased thrombus size. This is likely attributable to increased platelet aggregability and contribution to clot formation, despite reduced adhesion."

Biosimilar • Hematological Malignancies • Venous Thromboembolism

Iron substitution in the treatment of chronic heart failure. (PubMed, Swiss Med Wkly) - "In addition, screening for iron deficiency is recommended. Intravenous ferric carboxymaltose should be considered for treating iron deficiency in ambulatory symptomatic patients with reduced left ventricular ejection fraction in order to alleviate heart failure symptoms, and to improve exercise capacity and quality of life."

Journal • Biosimilar • Cardiovascular • Gene Therapies • Heart Failure

Ferric carboxymaltose therapy in IBD patients with iron deficient anaemia: Real-life data from Germany (ECCO-IBD 2018) - "Conclusion Ferinject therapy was proven to be safe and effective in a large cohort of patients with IBD-associated anaemia in routine practice. Rapid, high-dose application is convenient for physicians and reduces patients time lost from work."

Clinical • Inflammatory Bowel Disease

A Case of Hypophosphatemia Due to Ferric Carboxymaltose Induced Renal Phosphate Wasting (KIDNEY WEEK 2017) - "FCM is a convenient treatment option for iron deficiency as it only requires a single infusion. Clinicians should be aware of the association between FCM and hypophosphatemia, and consider this diagnosis in patients who present with symptoms consistent with hypophosphatemia after infusion."

Clinical • Renal Disease

Intravenous ferric carboxymaltose for heart failure with iron deficiency. (PubMed, Eur J Heart Fail) - No abstract available.

Journal • Biosimilar • Cardiovascular • Heart Failure

Beneficial effect of intravenous iron, ferric carboxymaltose, in heart failure (HEART FAILURE 2018) - "Although we did not find any evidence of anemia or iron deficiency in the rat model of post-MI HF, we observed positive effect of iron supplementation in such setting and we confirmed that such supplementation is safe."

Acute Coronary Syndrome • Biosimilar • Cardiovascular • Heart Failure

Iron Deficiency Anemia (IDA) in Patients with Heart Failure (HFSA 2018) - "Description The program will address the following: Types of patients who can have iron deficiency anemia (IDA) and its prevalence Pathophysiology, causes and consequences of IDA Impact of IDA in patients with heart failure Differential diagnosis of IDA using laboratory assessments, signs and symptoms The treatment goals and available treatments for IDA Efficacy and safety of Injectafer® (ferric carboxymaltose injection) in patients with IDA. Sponsored by Daiichi Sankyo "

Clinical • Heart Failure

"In pts w acute isovolemic #anemia after #gastrectomy, ferric carboxymaltose may improve #hemoglobin response https://t.co/UxNlK3da9E"

Biosimilar

Effect of Ferric Carboxymaltose on Exercise Capacity in Patients with Chronic Heart Failure and Iron Deficiency. (PubMed, Circulation) - P3; "Treatment with intravenous FCM in patients with HF and iron deficiency improves iron stores. Although a favorable effect on peak VO2 was observed on FCM, compared with standard of care in the primary analysis, this effect was highly sensitive to the imputation strategy for peak VO2 among patients who died. Whether FCM is associated with an improved outcome in these high-risk patients needs further study."

Biomarker • Journal • Biosimilar • Heart Failure

Iron-regulatory proteins secure iron availability in cardiomyocytes to prevent heart failure. (PubMed) - "ID in cardiomyocytes impairs mitochondrial respiration and adaptation to acute and chronic increases in workload. Iron supplementation restores cardiac energy reserve and function in iron-deficient hearts."

Journal • Acute Coronary Syndrome • Biosimilar • Heart Failure

Renal function in patients with non-dialysis chronic kidney disease receiving intravenous ferric carboxymaltose: an analysis of the randomized FIND-CKD trial. (PubMed) - BMC Nephrol - P3; "Intravenous FCM at doses that maintained ferritin levels of 100-200 μg/L or 400-600 μg/L did not negatively impact renal function (eGFR) in patients with ND-CKD over 12 months versus oral iron, and eGFR remained stable. These findings show no evidence of renal toxicity following intravenous FCM over a 1-year period."

Journal • Biosimilar • Chronic Kidney Disease • Renal Disease

Treating Anemia in the Preanesthesia Assessment Clinic: Results of a Retrospective Evaluation. (PubMed, Anesth Analg) - "An anemia clinic within the preanesthesia assessment clinic is a feasible and effective approach to treat preoperative anemia. The IVI supplementation was safe but was associated with decreased RBC transfusions in gynecology/obstetric patients only. The conclusions from this retrospective analysis have to be tested in prospective, controlled trials."

Journal • Retrospective data

Preoperative Epoetin-α with Intravenous or Oral Iron for Major Orthopedic Surgery: A Randomized Controlled Trial. (PubMed, Anesthesiology) - "After preoperative administration of erythropoietin, body iron stores and stimulation of the erythropoiesis were greater with intravenous ferric carboxymaltose than with oral ferrous sulfate supplementation."

Clinical • Journal

Differences between intravenous iron products: focus on treatment of iron deficiency in chronic heart failure patients. (PubMed, ESC Heart Fail) - "Evaluation of published clinical and non-clinical studies with different i.v. iron products in this review suggests that study results obtained with one i.v. iron product should not be assumed to be equivalent to other i.v. iron products that lack comparable study data in CHF. Without head-to-head clinical studies proving the therapeutic equivalence of other i.v. iron products with ferric carboxymaltose, in the highly vulnerable population of heart failure patients, extrapolation of results and substitution with a different i.v. iron product is not recommended."

Clinical • Journal • Review

Persistent Isolated Hypophosphatemia after Intravenous Ferric Carboxymaltose Infusion in a Patient with Total Gastrectomy/Roux-en-Y (ENDO 2019) - "Although gastrectomy with poor nutrition may cause hypophosphatemia, it is worth considering other etiologies in the setting of persistently low phosphorus levels. With correlative evidence of high urinary phosphorus excretion in the setting of low serum phosphorus and elevated FGF23, we believe that IV ferric carboxymaltose infusion may have been a major contributor to hypophosphatemia in our patient. FGF23 is known to be a “phosphatonin” and ferric carboxymaltose may inhibit FGF23 degradation in osteocytes leading to an increase in its levels."

Clinical

Effects of Iron Isomaltoside versus Ferric Carboxymaltose on Hormonal Control of Phosphate Homeostasis: The PHOSPHARE-IDA04/05 Randomized Controlled Trials (ENDO 2019) - "FCM but not IIM also induced changes in vitamin D and calcium homeostasis that triggered secondary hyperparathyroidism, which likely contributed to persistence of hypophosphatemia. Consistent with case reports of pathological fractures following FCM use, FCM also induced significant elevations of biomarkers of bone turnover that are associated with osteomalacia."

Clinical

Incidence of hypophosphatemia in patients with inflammatory bowel disease treated with iron isomaltoside or ferric carboxymaltose: Results of a prospective cluster randomised cohort study (ECCO-IBD 2019) - "The presence of moderate to severe hypophosphatemia beyond 6 weeks is a clinical concern that needs further investigation. The Results were significant compared with IIM."

Clinical

Update of a network meta-analysis of efficacy and safety of different intravenous iron compounds in patients with IBD and anaemia (ECCO-IBD 2019) - "Here, we searched for new data to augment a first network metaanalysis (NMA) and systematic review of IV iron preparations [ferric carboxymaltose (FCM), ferumoxytol (FOX), iron sucrose/saccharate (IS), iron isomaltoside (ISM) and iron dextran (IDX)] approved in IBD, carried out in 2016.1 MethodsUsing the same methodology, we searched PUBMED, SCOPUS, Web of Science and Cochrane databases to identify articles published from Jul 2016 to August 2018. The totality of evidence showed that further studies are unlikely to overturn this result. Nevertheless, evidence from comprehensive head-to-head studies is needed to establish the comparative efficacy of different IV iron compounds in IBD patients with IDA."

Retrospective data

The comparative safety of different intravenous iron preparations in inflammatory bowel disease: a systematic review and network meta-analysis (ECCO-IBD 2019) - "We compared the tolerability of different IV iron therapies for IDA in IBD [ferric carboxymaltose (FCM), ferumoxytol (FOX), iron sucrose (IS), iron isomaltoside (ISM) and iron dextran (IDX)] in a systematic review and network meta-analysis (NMA). No severe hypophosphatemia-related bone manifestations occurred in the RCTs or other prospective studies. Further comprehensive trials are needed for head-to-head comparison of the safety of different IV iron substances."

Retrospective data • Review