DEMONSTRATED TOLERABILITY AND SAFETY

Adverse events (AEs) reported during the 16-week randomized period of the pivotal trial1

  • The most common adverse event was diarrhea (20.5%), the majority of which was mild to moderate in severity1,2
  • Incidence of hypophosphatemia, reported as a treatment-related AE, occurred in 1% of patients treated with AURYXIA® (ferric citrate) (1 patient) and 2% of patients treated with placebo (2 patients)3

During the 16-week randomized period, mean serum phosphorus levels decreased and were maintained within a range recommended by clinical practice guidelines4

In a pooled analysis from 2 trials

  • Adverse reactions reported in 2 clinical trials in at least 5% of patients receiving AURYXIA (AURYXIA vs placebo, respectively): Discolored feces (22% vs 0%), diarrhea (21% vs 12%), constipation (18% vs 10%), nausea (10% vs 4%), abdominal pain (5% vs 2%), hyperkalemia (5% vs 3%)

Similar rate of discontinuations due to adverse reactions and similar incidence of serious adverse events (SAEs) between AURYXIA and placebo groups during the 16-week randomized period1

  • The most common adverse reaction leading to discontinuation of AURYXIA was diarrhea at 2.6%
  • None of the SAEs were suspected to be study-drug related1
  • SAEs (by system organ class) occurring in ≥2% of patients treated with AURYXIA included cardiac disorders (2.6%), infections and infestations (3.4%), injury, poisoning, and procedural complications (2.6%), metabolism and nutrition disorders (2.6%), nervous system disorders (3.4%), renal and urinary disorders (3.4%), and respiratory, thoracic and mediastinal disorders (3.4%)3
  • SAEs (by system organ class) occurring in ≥2% of patients treated with placebo included cardiac disorders (2.6%), infections and infestations (5.2%), and renal and urinary disorders (4.3%)3
Trial Design

A 16-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of AURYXIA for the treatment of iron deficiency anemia in adult patients with CKD not on dialysis. Patients were randomized to treatment with either AURYXIA (n=117) or placebo (n=117), had hemoglobin levels ≥9.0 g/dL and ≤11.5 g/dL and who were previously intolerant of or had inadequate therapeutic response to traditional oral iron supplements. The primary endpoint was the proportion of patients achieving a ≥1.0 g/dL increase in hemoglobin at any time point during the 16-week efficacy period. Use of oral iron, IV iron, and ESAs was not permitted at any time during the trial.

Studied in a Phase III pivotal trial of patients who previously failed oral iron therapy

Primary efficacy endpoint

  • Proportion of patients achieving an increase in hemoglobin concentration of ≥1.0 g/dL from baseline at any point through the end of the randomized period (Week 16)

Key secondary efficacy endpoints included1:

  • Mean changes in hemoglobin, TSAT, ferritin, and phosphorus from baseline to Week 16
  • Proportion of patients experiencing a sustained treatment effect on hemoglobin (≥0.75 g/dL mean change in hemoglobin from baseline over any 4-week period provided that an increase of at least 1.0 g/dL had occurred during that 4-week period)

Key inclusion criteria

  • Adult patients with CKD not on dialysis (eGFR <60 mL/min/1.73 m2) and iron deficiency anemia (hemoglobin ≥9.0 and ≤11.5 g/dL, ferritin ≤200 ng/mL and TSAT ≤25%) at screening
  • Intolerant of or have had an inadequate therapeutic response to oral iron supplements

Key exclusion criteria3

  • IV iron, ESAs, or blood transfusion administered within 4 weeks prior to screening
  • Serum phosphorus <3.5 mg/dL at screening
  • Cause of anemia other than iron deficiency or CKD
KDOQI=Kidney Disease Outcomes Initiative; eGFR=estimated Glomerular Filtration Rate.
References
  1. Fishbane S, Block GA, Loram L, et al. Effects of ferric citrate in patients with nondialysis-dependent CKD and iron deficiency anemia. J Am Soc Nephrol. 2017;28(6):1851-1858.
  2. Data on File 13, Keryx Biopharmaceuticals, Inc.
  3. Supplement to: Fishbane S, Block GA, Loram L, et al. Effects of ferric citrate in patients with nondialysis-dependent CKD and iron deficiency anemia. J Am Soc Nephrol. 2017;28(6):1851-1858.
  4. National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42(4 Suppl 3):S1-S201.