Safety and Efficacy of Intravenous Ferric Derisomaltose Compared to Iron Sucrose for Iron Deficiency Anemia in Patients with Chronic Kidney Disease With and Without Heart Failure

John G.F Cleland,Theresa Mcdonagh,Stephan Von Haehling,Paul R Kalra,Andrew P Ambrosy,Sunil Bhandari,Emma Court

doi:10.1016/j.amjcard.2021.04.042

Abstract

Ferric derisomaltose (FDI) is an intravenous (IV) high-dose iron formulation approved in the US for the treatment of iron deficiency anemia in adults who are intolerant of/have had an unsatisfactory response to oral iron, or who have non-dialysis-dependent chronic kidney disease (NDD-CKD). FERWON-NEPHRO was a randomized, open-label, multicenter clinical trial evaluating the safety and efficacy of a single infusion of FDI 1,000 mg versus up to 5 doses of iron sucrose (IS) 200 mg (recommended cumulative dose, 1,000 mg) over 8 weeks in patients with NDD-CKD and iron deficiency anemia. Of 1,525 patients included in the safety analysis, 244 (16%) had a history of heart failure (HF). Overall, the rate of serious or severe hypersensitivity reactions was low and did not differ between treatment groups. Cardiovascular adverse events (AEs) were reported for 9.4% of patients who had HF and 4.2% who did not. Time to first cardiovascular AE was longer following administration of FDI compared with IS (hazard ratio: 0.59 [95% CI: 0.37, 0.92]; p=0.0185), a difference that was similar in patients with or without HF (p=0.908 for interaction). Patients achieved a faster hematological response (assessed by changes in hemoglobin and ferritin concentrations, and increase in transferrin saturation) with FDI versus IS. In conclusion, in patients with NDD-CKD, a single infusion of FDI was safe, well tolerated, and was associated with fewer cardiovascular AEs and a faster hematological response, compared to multiple doses of IS. These effects were similar for patients with and without HF.

Highlights

Prime Global Agency’, Cambridge, UK, and funded by Pharmacosmos A/S, Holbæk, Denmark
Time to first cardiovascular adverse events (AEs) was longer following administration of Ferric derisomaltose (FDI) compared with iron sucrose (IS) (Figure 1)
The effect was similar in patients with heart failure (HF) or without HF and driven by fewer hospitalizations for HF (Table 2)

Summary

Introduction

Prime Global Agency’, Cambridge, UK, and funded by Pharmacosmos A/S, Holbæk, Denmark. In 2020, the US Food and Drug Administration (FDA) approved FDI for the treatment of iron deficiency anemia in adults who are either intolerant of or have had an unsatisfactory response to oral iron, or who have non-dialysisdependent chronic kidney disease (NDD-CKD). FDA approval was based on two randomized, open-label, multicenter trials, FERWON-IDA1 and FERWON-NEPHRO.[2] FERWON-IDA included younger patients (mean age 44 years) with iron deficiency anemia, mainly women (89%),[1] and only 16 had heart failure (HF) (unpublished data). For patients with HF, iron deficiency and anemia are common and associated with more severe symptoms, poorer quality of life, reduced exercise capacity, impaired renal function and a worse prognosis.[3,4,5,6,7,8,9] Randomized controlled trials conducted in patients with HF

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