AT KIDNEY WEEK 2016
CHICAGO (FRONTLINE MEDICAL NEWS) – Ferric citrate was safe and effective for treatment of iron-deficiency anemia in patients who had non–dialysis-dependent chronic kidney disease (NDD-CKD), based on data from a phase III, randomized, double-blind study.
The responses were durable, and none of the patients received erythropoiesis-stimulating agents (ESAs), presenter Pablo Pergola, MD, PhD, of Renal Associates, San Antonio, said in an interview at a meeting sponsored by the American Society of Nephrology.
The trial involved 234 anemic adults who had NDD-CKD and had not responded to oral iron supplements. The subjects were randomized to receive oral ferric citrate (n = 117) or placebo (n = 115) with meals (one patient did not receive placebo and laboratory data were lacking for one patient). The mean dose in the treatment arm was 5 pills per day.
The primary endpoint was the proportion of patients with hemoglobin (Hgb) greater than or equal to 1.0 g/dL anytime from baseline through week 16. Secondary endpoints included mean changes from baseline in Hgb, transferrin saturation, ferritin, and serum phosphate and evidence of sustained treatment effect based on target changes in Hgb with time.
Both arms were comparable at baseline for demographic and clinical characteristics, including phosphorus and hemoglobin levels and estimated glomerular filtration rate.
The primary endpoint was met by 51.2% of patients receiving ferric citrate and 19.1% of patients receiving placebo (P less than .001). All secondary efficacy endpoints were met, with statistically significant differences between the treatment and placebo arms, Dr. Pergola reported.
Serum phosphate level was significantly reduced from baseline at week 16 (–0.21 mg/dL; 95% confidence interval, –0.39 to –0.03 mg/dL; P equal to .02) in the active treatment group, and the levels remained in the normal range, he said.
During the 16-week treatment period and subsequent 8-week, open-label safety extension period, ferric citrate was well tolerated. Treatment-emergent adverse events (AEs), most commonly diarrhea, occurred in 93 (79.5%) and 75 (64.7%) patients in the treatment and placebo arms, respectively. Serious AEs developed in 14 (12.0%) and 13 (11.2%) of patients in the same respective order. Two deaths occurred, both in the treatment group. The deaths and serious AEs were not considered drug related.
Ferric citrate binds with dietary phosphate in the gastrointestinal tract. The resulting ferric phosphate is insoluble and is excreted. The remaining unbound ferric citrate increases serum iron parameters, including ferritin and transferrin saturation.
The findings potentially extend the therapeutic reach of the drug beyond its Food and Drug Administration–approved use for control of phosphorus levels in CKD patients on dialysis, Dr. Pergola said. The trial data will be used to seek approval for the oral iron medication as a treatment for iron-deficiency anemia in adults with NDD-CKD.
The study was sponsored by Keryx Biopharmaceuticals. Dr. Pergola is supported by honoraria and lecture fees from Akebia Therapeutics, Keryx, Relypsa, Vifor/Fresenius Pharma, and ZS Pharma.