Iron Deficiency Anemia CKD Not On Dialysis

Safety and tolerability profile
evaluated in a pivotal clinical trial

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

  • The most common AE was diarrhea (20.5%), the majority of which was mild to moderate in severity1,2

In a pooled analysis from 2 trials3

  • 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%)

During the 16-week randomized period, decreases in mean phosphorus levels were observed3

Mean phosphorus levels started and stayed within a range recommended by clinical practice guidelines4

In a pooled analysis from 2 trials

  • Incidence of hypophosphatemia, reported as a treatment-related adverse event, occurred in 1% of patients treated with AURYXIA (1 patient) and 2% of patients treated with placebo (2 patients)5

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 period1,3

  • The most common adverse reaction leading to discontinuation of AURYXIA was diarrhea at 2.6%3
  • 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%)5
  • 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%)5
Trial Design3

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, this trial evaluated the efficacy and safety of AURYXIA for the treatment of iron deficiency anemia in adult patients with CKD not on dialysis. Patients who were intolerant of or have had an inadequate therapeutic response to oral iron supplements, with hemoglobin ≥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).

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 were intolerant of or had inadequate response to traditional oral iron therapy

Primary efficacy endpoint3

  • 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 criteria3

  • 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 criteria5

  • 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 Quality Initiative; ESAs=erythropoiesis-stimulating agents; IV=intravenous; eGFR=estimated Glomerular Filtration Rate.

Indication

AURYXIA® (ferric citrate) is indicated for:

  • The treatment of iron deficiency anemia in adult patients with chronic kidney disease not on dialysis

Important Safety Information

CONTRAINDICATION

AURYXIA® (ferric citrate) is contraindicated in patients with iron overload syndromes, e.g., hemochromatosis

WARNINGS AND PRECAUTIONS

  • Iron Overload: Increases in serum ferritin and transferrin saturation (TSAT) were observed in clinical trials with AURYXIA in patients with chronic kidney disease (CKD) on dialysis treated for hyperphosphatemia, which may lead to excessive elevations in iron stores. Assess iron parameters prior to initiating AURYXIA and monitor while on therapy. Patients receiving concomitant intravenous (IV) iron may require a reduction in dose or discontinuation of IV iron therapy
  • Risk of Overdosage in Children Due to Accidental Ingestion: Accidental ingestion and resulting overdose of iron-containing products is a leading cause of fatal poisoning in children under 6 years of age. Advise patients of the risks to children and to keep AURYXIA out of the reach of children

ADVERSE REACTIONS

The most common adverse reactions reported with AURYXIA in clinical trials were:

  • Iron Deficiency Anemia in CKD Not on Dialysis: Discolored feces (22%), diarrhea (21%), constipation (18%), nausea (10%), abdominal pain (5%) and hyperkalemia (5%)

SPECIFIC POPULATIONS

  • Pregnancy and Lactation: There are no available data on AURYXIA use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. However, an overdose of iron in pregnant women may carry a risk for spontaneous abortion, gestational diabetes and fetal malformation. Data from rat studies have shown the transfer of iron into milk, hence, there is a possibility of infant exposure when AURYXIA is administered to a nursing woman

To report suspected adverse reactions, contact Akebia Therapeutics, Inc. at 1-844-445-3799

Please see full Prescribing Information

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, Akebia Therapeutics, Inc.
  3. AURYXIA [package insert]. Cambridge, MA: Akebia Therapeutics, Inc.; 2017.
  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.
  5. 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.