July 24, 2014
Phosphate Binder Ups Iron in Dialysis Patients
Featuring: Kenar Jhaveri, Physician, North Shore University Hospital
A novel agent cleared phosphate while boosting iron levels in dialysis patients, a phase III study showed.
The investigational ferric citrate (Zerenex) had comparable efficacy in terms of phosphate clearance to two other common phosphate binders in a 52-week study, according to Julia Lewis, MD, of Vanderbilt University Medical Center in Nashville, Tenn., and colleagues.
But those on the new drug had higher mean iron parameters than patients on calcium acetate (Phoslo) or sevelamer carbonate (Renvela) or a combination of the two, they reported in the Journal of the American Society of Nephrology.
The drug -- an oral ferric iron-based phosphate binder -- also bested placebo in phosphorus control in a 4-week extension of the trial, they reported.
"Ferric citrate is an efficacious and safe phosphate binder that increases iron stores and reduces intravenous iron and erythropoietin-stimulating agent (ESA) use while maintaining hemoglobin," the researchers wrote.
Since dialysis patients are typically complicated by both hyperphosphatemia and anemia, ferric citrate was designed to clear phosphate while simultaneously increasing iron levels.
In the 52-week study, the researchers randomized 441 dialysis patients to either ferric citrate (a 1-g tablet with 210 mg of ferric iron) or to an active control of either calcium acetate or sevelamer carbonate alone or in combination. That was followed by a 4-week trial in which 192 patients were re-randomized to either ferric citrate or to placebo.
The primary analysis looked at phosphate control during this 4-week placebo period, and found better results with the drug, with a mean treatment difference of -2.2 mg/dL (P<0.001).
In the 52-week study, the researchers saw similar phosphate control between ferric citrate and active control groups, but those on the novel agents had higher mean iron parameters (P<0.001 for both):
• Ferritin: 899 ng/mL versus 628 mg/dL
• Transferrin saturation: 39% versus 30%
Those on ferric citrate also required less intravenous iron (mean 12.95 mg versus 26.88 mg per week, P<0.001) and fewer ESAs (5,306 units/week versus 6,951 units/week, P=0.04). Hemoglobin levels were also higher with ferric citrate, they added.
More patients did, however, discontinue the study drug compared with the other active controls (33% versus 23%), most commonly in the first week of therapy and because of nonserious gastrointestinal adverse events such as diarrhea and bloating, the researchers said.
And those on the novel agent had fewer serious adverse events than those in the active control group (39% versus 49%).
"No other approved phosphate binder increases iron stores and decreases IV iron and ESA usage," the researchers concluded.
Kenar Jhaveri, MD, a nephrologist at Hofstra North Shore-LIJ School of Medicine in Great Neck, N.Y., noted the benefits of having a single oral medication to help with two effects of chronic kidney disease, but noted some caveats.
"The study was mainly done to [assess] this agent as a phosphate binder and not solely for anemia," said Jhaveri, who was not involved in the study. "In addition, citrate has properties of anticoagulation and lowering serum calcium levels. It was good to see that the calcium levels stayed relatively stable in the study. Long-term effects on calcium and anticoagulation might be important to look at."
An earlier phase II study looked at ferric citrate in iron-deficiency anemia and found significant increases in transferrin saturation. The drug also lowered phosphate levels in that trial. A spokesperson for Keryx said the drug is being studied for both indications in parallel tracks of development.
Drugmaker Keryx biopharmaceuticals has filed a new drug application for Zerenex with the FDA. The Prescription Drug User Fee Act (PDUFA) date was recently extended to Sept. 7.
The study was supported by Keryx Biopharmaceuticals.
The authors disclosed relevant relationships with Keryx Biopharmaceuticals