Safety: Pharmacodynamics in AURYXIA

AURYXIA has been shown to increase iron parameters, including TSAT and ferritin1

  • AURYXIA has a warning for iron overload which may lead to excessive elevation in iron stores; serum ferritin and TSAT should be assessed prior to initiating and monitored while on therapy.1*
    • During the 52-week Active Control Period in the Phase III trial in which concomitant use of IV iron was permitted1:
    • Gradual increases in iron parameters occurred over the first 3-6 months and then plateaued2

*TSAT=transferrin saturation.

Assess iron parameters prior to initiating AURYXIA as a phosphate binder and monitor while on therapy1

AND

In patients receiving IV iron, a reduction in dose or discontinuation of IV iron therapy may be required1

Mean TSAT levels for AURYXIA vs Active Control3†

AURYXIA (n=252)

ACTIVE CONTROL (n=137)

Mean TSAT levels for AURYXIA vs Active ControlMean TSAT levels for AURYXIA vs Active Control

Mean TSAT increased from 31.3% at baseline to 39.2% at Week 52 (~8%)

Active Control=sevelamer carbonate and/or calcium acetate.

Mean serum ferritin levels for AURYXIA vs Active Control3†

AURYXIA (n=252)

ACTIVE CONTROL (n=137)

Mean serum ferritin levels for AURYXIA vs Active ControlMean serum ferritin levels for AURYXIA vs Active Control

Mean serum ferritin increased from 593 ng/mL at baseline to 895 ng/mL at Week 52 (302 ng/mL)

Active Control=sevelamer carbonate and/or calcium acetate.

Considerations when evaluating iron parameters

  • Is the patient on concomitant IV iron that may affect lab results?
  • If the patient is not on IV iron, when was the last dose?
    • Have they been off IV iron for an extended period of time?
  • Do you look at trends of TSAT and/or ferritin increases when you stop IV iron?
  • Was there a recent/current inflammatory event that impacted iron parameters?
  • Is the lab value being impacted by the timing of the blood draw?

See how AURYXIA helped patients reach their target goals

AURYXIA helped patients reach and stay in the range of 3.5-5.5 mg/dL during a 56-week trial.4,5
Patients had a mean serum phosphorus level of 7.41 mg/dL at baseline and 4.88 mg/dL at Week 56.4

EXAMINE EFFICACY

See trial design

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ADVERSE REACTIONS

Trial design1,6

A multicenter, randomized, open-label, Phase III trial evaluated the safety and efficacy of AURYXIA as a phosphate binder in controlling serum phosphorus levels in adult patients with CKD on hemodialysis and peritoneal dialysis over 56 weeks. Eligible patients were on dialysis for ≥3 months before screening, were prescribed 3 to 18 pills/day of commercially available phosphate binder, and had serum ferritin <1000 ng/mL, serum TSAT <50%, and serum phosphorus ≥2.5 and ≤8.0 mg/dL at the screening visit. Patients who were intolerant to calcium acetate and sevelamer carbonate were not included in the trial.

The safety and efficacy of AURYXIA was studied in the 52-week Active Control Period (AURYXIA n=292, Active Control n=149). At the final Active Control Period visit, AURYXIA patients were re-randomized to either continue AURYXIA treatment or receive placebo as part of the Placebo-Controlled Period (AURYXIA n=96, placebo n=96). The primary endpoint of the pivotal trial was the change in serum phosphorus from baseline (Week 52) to Week 56 between AURYXIA and placebo in the 4-week Placebo-Controlled Period.

CKD=chronic kidney disease; TSAT=transferrin saturation; Active Control=sevelamer carbonate and/or calcium acetate.

IMPORTANT SAFETY INFORMATION AND INDICATION

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:

  • Hyperphosphatemia in CKD on Dialysis: Diarrhea (21%), discolored feces (19%), nausea (11%), constipation (8%), vomiting (7%) and cough (6%)

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

INDICATION

AURYXIA® (ferric citrate) is indicated for:

  • The control of serum phosphorus levels in adult patients with chronic kidney disease on dialysis

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

Please see full Prescribing Information

REFERENCES

  1. AURYXIA [package insert]. Cambridge, MA: Akebia Therapeutics, Inc.; 2021.
  2. Umanath K, Jalal DI, Greco BA, et al; for Collaborative Study Group. Ferric citrate reduces intravenous iron and erythropoiesis-stimulating agent use in ESRD. J Am Soc Nephrol. 2015;26(10):2578-2587.
  3. Data on File 2, Akebia Therapeutics, Inc.
  4. Data on File 1, Akebia Therapeutics, Inc.
  5. 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.
  6. Umanath K, Sika M, Niecestro R, et al; for Collaborative Study Group. Rationale and study design of a three period, 58-week trial of ferric citrate as a phosphate binder in patients with ESRD on dialysis. Hemodial Int. 2013;17(1):67-74.
  7. Data on File 29, Akebia Therapeutics, Inc.
  8. Data on File 30, Akebia Therapeutics, Inc.