Auryxia (ferric citrate) - 2 Indications

Scroll down for more information on each indication:

• for the treatment of hyperphosphatemia in patients with chronic kidney disease; approved September 2014
• for iron deficiency anemia in adult patients with chronic kidney disease not on dialysis; approved November 2017

General Information

Auryxia is a phosphate binder indicated for the control of serum phosphorus levels in adult patients with chronic kidney disease on dialysis.

Auryxia is an iron replacement product indicated for the treatment of iron deficiency anemia in adult patients with chronic kidney disease not on dialysis

Scroll down for information on dosing/administration for each indication.

Mechanism of Action

Hyperphosphatemia in Chronic Kidney Disease on Dialysis: Ferric iron binds dietary phosphate in the GI tract and precipitates as ferric phosphate. This compound is insoluble and is excreted in the stool. By binding phosphate in the GI tract and decreasing absorption, ferric citrate lowers the phosphate concentration in the serum.

Iron Deficiency Anemia in Chronic Kidney Disease Not on Dialysis: Ferric iron is reduced from the ferric to the ferrous form by ferric reductase in the GI tract. After transport through the enterocytes into the blood, oxidized ferric iron circulates bound to the plasma protein transferrin, and can be incorporated into hemoglobin

Side Effects

Adverse effects associated with the use of ferric citrate may include, but are not limited to, the following:

• Diarrhea
• Discolored feces
• Constipation
• Nausea
• Vomiting

Indication 1 - for the treatment of hyperphosphatemia in patients with chronic kidney disease

approved September 2014

Dosing/Administration

Ferric citrate is supplied as a tablet for oral administration. The recommended starting dose is two tablets orally three times per day with meals. Serum phosphorus levels should be monitored and the dose of ferric citrate titrated in decrements or increments of one to two tablets per day as needed to maintain serum phosphorus at target levels, up to a maximum dose of 12 tablets daily. Dose can be titrated at one-week or longer intervals. 

Clinical Trial Results

Fixed-Dose Trial: Following a one- to two-week washout from all phosphate-binding agents, 154 patients with hyperphosphatemia (mean serum phosphorus of 7.5 mg/dL) and chronic kidney disease on dialysis were randomized in a 1:1:1 ratio to 1, 6 or 8 tablets/day of ferric citrate for four weeks. Ferric citrate was administered with meals. Subjects receiving one tablet/day were instructed to take it with their largest meal of the day, and subjects on six or eight tablets/day took divided doses in any distribution with meals. Dose-dependent decreases in serum phosphorus were observed by day seven and remained relatively stable for the duration of treatment. The demonstrated reductions from baseline to week four in mean serum phosphorus were significantly greater with six and eight tablets/day than with one tablet/day (p<0.0001). Mean reduction in serum phosphorus at week four was 0.1 mg/dL with one tablet/day, 1.9 mg/dL with six tablets/day and 2.1 mg/dL with eight tablets/day. 

Long-term, Randomized, Controlled, Safety and Efficacy Trial: After the two-week washout period during which phosphate binders were held, patients with a mean serum phosphorus of 7.5 mg/dL during washout were randomized 2:1 to ferric citrate (N=292) or active control (calcium acetate and/or sevelamer carbonate; N=149). The majority of subjects were on hemodialysis. The starting dose of ferric citrate was six tablets/day with meals. The starting dose of active control was the patient’s dose prior to the washout period. The dose of phosphate binder was increased or decreased as needed to maintain serum phosphorus levels between 3.5 and 5.5 mg/dL, to a maximum of 12 tablets/day. Following completion of the 52-week active-controlled phase, ferric citrate-treated patients were eligible to enter a four-week placebo-controlled randomized withdrawal phase, in which patients were re-randomized in a 1:1 ratio to receive ferric citrate (N=96) or placebo (N=96). The study met the primary endpoint by demonstrating a highly statistically significant change in serum phosphorus vs. placebo over the four-week placebo-control period. During the placebo-control period, the serum phosphorus concentration rose by 2.2 mg/dL in the placebo arm relative to the ferric citrate arm. Ferric citrate also demonstrated statistically significant increases in serum ferritin and transferrin saturation (TSAT) and significant reductions in the use of IV iron and erythropoietin stimulating agents vs. an active control of sevelamer carbonate and/or calcium acetate over the 52-week active control period of the study. In addition, mean hemoglobin levels were higher in subjects treated with Zerenex as compared to subjects treated with active control.

Indication 2 - for iron deficiency anemia in adult patients with chronic kidney disease not on dialysis

approved November 2017

Dosing/Administration

Starting dose is 1 tablet orally 3 times per day with meals. Adjust dose as needed to achieve and maintain hemoglobin goal, up to a maximum of 12 tablets daily.

Clinical Trial Results

The efficacy of Auryxia for the treatment of iron deficiency anemia in adult patients with CKD not on dialysis was demonstrated in a 24-week study consisting of a 16-week, randomized, double-blind, placebo-controlled, efficacy period followed by an 8-week open-label safety extension period in which all patients remaining in the study, including the placebo group, received Auryxia. Patients with eGFR <60 mL/min/1.73m2 , who were intolerant of or have had an inadequate therapeutic response to oral iron supplements, with Hgb ≥9.0 g/dL and ≤11.5 g/dL, serum ferritin ≤200 ng/mL and TSAT ≤25% were enrolled. Patients were randomized to treatment with either Auryxia (n=117) or placebo (n= 117). Dosing with Auryxia or placebo was initiated at 3 tablets/day with meals. Dose titration could occur at Weeks 4, 8 and 12 during Randomized Period, and at Weeks 18 and 20 during Safety Extension Period based on Hgb response. Use of oral or intravenous iron, erythropoiesis stimulating agents (ESAs) was not permitted at any time during the study. 

The main efficacy outcome measure was the proportion of subjects achieving an increase in Hgb of ≥1.0 g/dL at any time point between baseline and the end of the 16-week Randomized Period. During the 16-week randomized period 49% of subjects in the Auryxia arm and 15% of subjects in the placebo arm (p <0.001) had a mean change in hemoglobin from baseline ≥0.75 g/dL over any 4-week time period provided that an increase of at least 1.0 g/dL had occurred during that 4- week period. Increases in mean hemoglobin (0.75 ± 0.09 g/dL), serum ferritin (163 ± 9 ng/mL) and transferrin saturation (18 ± 1%) were observed from baseline during the 16-week randomized period in the Auryxia arm.