Rockwell Medical’s iron replacement drug Triferic (ferric pyrophosphate citrate) can effectively deliver iron and maintain hemoglobin levels without increasing iron stores, and reduce the need for ESAs, according to a study published online July 8 in Kidney International.

Update: Two studies published recently in Nehrology Dialysis Transplantation also showed the benefits of Triferic.

About the study
The PRIME study, lead by Rockwell’s chief scientific officer Ajay Gupta, was a nine-month, prospective, randomized, placebo-controlled, double-blinded, multi-center study conducted in the United States to determine the safety and efficacy of Triferic as a treatment to reduce ESA while maintaining hemoglobin. Iron-replete chronic hemodialysis patients were randomized to dialysate containing Triferic-iron versus conventional dialysate. A total of 103 patients received blinded study drug (52 Triferic, 51 Placebo).

Toxic effects of IV iron preparations in CKD patients 

Results
The primary objective of the PRIME study was to determine whether regular administration of Triferic via dialysate reduced the need for erythropoiesis stimulating agents by optimizing iron delivery and maintaining iron balance. The primary endpoint was the percent change in ESA dose from baseline to end of treatment (final two weeks of treatment period).

After adjusting for differences in baseline hemoglobin, the Triferic arm required 35% less ESA dose compared to placebo.

“The ESA requirement of the [Triferic] group progressively decreased from six months forward relative to the placebo group, suggesting that the 9-month study duration likely captured a partial effect of the potential of FPC to reduce ESA use,” the study authors wrote.

Interpreting tests of iron sufficiency in ESRD patients 

The ESA sparing effect from Triferic was observed without an increase in serum ferritin or transferrin saturation above the baseline values. In a pre-specified secondary analysis of the 20% of patients who were hyporesponsive to ESA ( > 13,000 epoetin units/week), the Triferic group used 74.4% (p=NS) less ESA than placebo, further confirming the effect on ESA observed in the entire study cohort.

“The ESA-sparing benefit of FPC [Triferic] is likely related to its direct donation of iron to transferrin with every hemodialysis treatment, allowing it to overcome the hepcidin-induced RE-block and functional iron deficiency that occur with uremic inflammation,” the study authors wrote. “The rapid and direct binding of FPC iron to transferrin is in contrast to i.v. iron where the iron-carbohydrate complexes undergo uptake by the RE [reticuloendothelial] system because of their particulate nature and are subject to sequestration in states of inflammation.”