Two more studies have demonstrated that Rockwell Medical's Triferic (ferric pyrophosphate citrate, or FPC) delivered via dialysate during hemodialysis replaces iron loss, maintains hemoglobin, and does not increase iron stores. A smaller study published online July 8 in Kidney International found similar results.
The CRUISE studies, published in Nephrology Dialysis Transplantation, were randomized, single blind, placebo controlled, efficacy and safety studies in chronic hemodialysis patients. Triferic was added to the bicarbonate hemodialysis concentrate while placebo patients received standard hemodialysate without Triferic. A total of 599 patients participated in both studies with 290 randomized to receive Triferic and 295 to placebo. Patients completed the Phase 3 study when they met pre-specified anemia centered criteria or lasted 48 weeks without achieving the criteria. After completing randomized treatment, patients entered open-label treatment.
"Our study is important and should be of interest to the entire renal community, including patients, because it shows Triferic is an effective iron agent that is able to maintain hemoglobin without inducing iron overload," said Steven Fishbane, lead author and Chief of the Division of Kidney Diseases and Hypertension at North Shore University Hospital and Long Island Jewish Medical Center. "Triferic is administered at each dialysis session and its iron is immediately donated to transferrin, very similar to the slower natural way iron is used in the body to maintain hemoglobin."
The primary objective of the CRUISE studies was to determine whether regular administration of Triferic via dialysate could maintain hemoglobin concentrations by optimizing iron delivery and maintaining iron balance. The primary endpoint was the mean change in hemoglobin from baseline to the end-of-treatment (EoT) defined as the average of all hemoglobin values obtained during the last one-sixth (1/6th) of the time spent in the randomized stage of treatment (Stage 2). Both studies successfully met the primary endpoint with a treatment difference of 0.4 g/dL in hemoglobin concentration in favor of Triferic (P=0.011 for individual studies, 95% confidence interval 0.1 to 0.6 g/dL). During the randomized treatment phase, hemoglobin concentrations remained stable in the Triferic treated group while declined in the placebo group. The safety profile of Triferic was similar to placebo treated patients, with both groups experiencing similar proportions of adverse events. The most frequent adverse event was procedural hypotension which was present in 21.6% of Triferic patients and 19.2% of placebo treated patients. No serious adverse events or deaths were attributed to Triferic.
Affects on ESA dosing
"The proportions of patients who required protocol mandated changes in ESA dose were similar in the Triferice group (43.5%) and placebo (46.0%) groups, but the indications for change differed," the authors wrote. "Among these patients, an increase in Hgb to >12.0 g/dL led to protocol mandated decreases in ESA dose in 55.4% of FPC treated patients as compared with 38.4% of placebo-treated patients (P = 0.007), a difference consistent with improved delivery of iron for erythropoiesis by FPC relative to placebo. A decrease in Hgb to <9.0 g/dL led to protocol-mandated increases in ESA dose in 43.5% of patients receiving placebo compared with 30.0% of those receiving FPC (P = 0.02), a divergence suggesting improved delivery of iron for erythropoiesis by FPC relative to placebo." -by Rebecca Zumoff