Keryx Biopharmaceuticals Announces Presentation of Post-Hoc Data From Phase 3 Study of Auryxia® (Ferric Citrate) in Adults With Iron Deficiency Anemia and Non-dialysis Dependent Chronic Kidney Disease
- Oral presentation showed impact of ferric citrate on a phosphate-regulating hormone, FGF23
- Poster presentation showed effect of ferric citrate when dosed to increase hemoglobin on serum phosphorus in people with normal baseline phosphorus levels
- Data presented today at the
American Society of Nephrology(ASN) 2017 Kidney Week
In the U.S., Auryxia is
“A highlight for us at this year’s Kidney Week is Dr. Block’s oral presentation, which suggests that ferric citrate may reduce FGF23 through several, potentially independent pathways in patients with CKD and iron deficiency anemia,” said
“FGF23 is emerging as an important biomarker of chronic kidney disease,” said
The two post-hoc analyses were derived from a 16-week, randomized, placebo-controlled Phase 3 study that evaluated ferric citrate for the treatment of iron deficiency anemia in adults with non-dialysis dependent chronic kidney disease. As previously published in
Oral presentation examining effect of ferric citrate on FGF23
“Ferric Citrate Reduced FGF23 in Patients with Non-Dialysis Dependent Chronic Kidney Disease (NDD-CKD) and Iron Deficiency Anemia (IDA) Irrespective of the Change in Serum Phosphate (P)” Oral presentation #TH-OR038.
FGF23 is a phosphate regulating hormone that is associated with chronic kidney disease progression1. It increases as chronic kidney disease progresses and increases with the presence of iron deficiency anemia2. Elevated levels of this hormone are associated with increased risk of cardiovascular disease and death in chronic kidney disease patients3. There are many overlapping and complicating factors that can impact FGF23, including changes in phosphorus levels and iron levels in the body4.
In the oral presentation, after 16 weeks of treatment with Auryxia in adults with non-dialysis dependent chronic kidney disease and iron deficiency anemia, FGF23 levels were significantly reduced (Table 1). Post-hoc analysis of a Phase 3 study further examined if the reductions in FGF23 levels tracked with baseline serum phosphorus and baseline iron levels. Data presented at the meeting today showed reductions in FGF23 levels occurred irrespective of a patient’s baseline phosphorus level or baseline iron measure level (Table 2). These data suggest Auryxia may reduce FGF23 via several, potentially independent pathways in patients with chronic kidney disease and iron deficiency anemia via reductions in serum phosphorus levels and/or increases in iron stores.
Table 1: Effect of Ferric Citrate on FGF23, Phase 3 Study
(n=116, cFGF23, n=117 iFGF23)
(n=85 cFGF23, n=86 iFGF23)
(n=113, cFGF23, n=114 iFGF23)
(n=79, cFGF23, n=80 iFGF23)
|Median iFGF23, pg/mL||134.0||105.0||134.3||119.5||<0.001|
|Median cFGF23, RU/mL||364.0||232.5||305.8||309.4||<0.001|
|FGF23=fibroblast growth factor 23; cFGF = c-terminal FGF, iFGF=intact FGF
|*n dependent upon number of laboratory values available
|** Between-group changes were evaluated from baseline to the end of week 16 using Wilcoxon rank sum test for nonparametric data.
Table 2: Effect of Ferric Citrate on FGF23 by baseline phosphorous level, baseline iron level, Phase 3 Study
|BL P < 3.5 mg/dL||BL P 3.5 <4.5 mg/dL||BL P 4.5 <5.5 mg/dL||BL P > 5.5 mg/dL||BL TSAT <20%||BL TSAT > 20%|
|16 wks median||85.0||102.2||152.0||156.6||101.4||113.0|
|16 wks median||173.1||198.3||328.0||592.1||259.3||207.1|
|*P-values are from a non-parametric (Wilcoxon signed-rank) test
|BL P = baseline phosphorus level|
Poster presentation examining effect of ferric citrate on normal phosphorus levels
“Ferric Citrate Lowered Serum Phosphate Only When Elevated in Patients with Non-Dialysis Dependent (NDD) CKD and Iron Deficiency Anemia (IDA)” Poster # TH-PO514.
In a poster presentation today, a post-hoc analysis of this Phase 3 study was conducted to further examine the effect of ferric citrate on serum phosphorus when patients were stratified by baseline phosphorus, kidney function or FGF23 levels. The analysis showed that in patients treated with ferric citrate to increase hemoglobin levels, the mean reduction in serum phosphorus differed by baseline phosphorus levels. Specifically, serum phosphorus levels decreased only in patients with elevated serum phosphorus at baseline, especially those with the highest baseline serum phosphorus levels. Importantly, in patients with normal phosphate levels, there was no discernible change in phosphorus when treated with ferric citrate (Table 3). These data provide further evidence that when ferric citrate was used as a treatment for iron deficiency anemia in patients with normal phosphorus levels at baseline, mean phosphorus remained in the normal range (3.5 mg/dL and 5.5 mg/dL) and the risk of hypophosphatemia was low.
Table 3: Change in serum phosphorus by baseline phosphorous levels
|BL P <3.5 mg/dL||BL P 3.5 - <4.5 mg/dL||BL P 4.5 - <5.5 mg/dL||BL P >5.5 mg/dL|
|Serum P (n=115)||Change from baseline to week 16||+0.24||-0.26||-0.97||-1.74|
|** p-values are from a parameter t-test
|BL P = baseline phosphorus level
About Auryxia® (ferric citrate) tablets
Auryxia (ferric citrate) was approved by the
Use of ferric citrate in patients with IDA, NDD-CKD, as highlighted above, is investigational and has not been determined to be safe or efficacious.
IMPORTANT U.S. SAFETY INFORMATION FOR AURYXIA® (ferric citrate)
Contraindication: Patients with iron overload syndrome, e.g. hemochromatosis, should not take Auryxia®.
Iron Overload: Iron absorption from Auryxia may lead to increased iron in storage sites. Iron parameters should be monitored prior to and while on Auryxia. Patients receiving IV iron may require a reduction in dose or discontinuation of IV iron therapy.
Accidental Overdose of Iron: Accidental overdose of iron containing products is a leading cause of fatal poisoning in children under 6 years of age. Keep Auryxia away from children as it contains iron. Call a poison control center or your physician in case of an accidental overdose in a child.
Patients with Gastrointestinal Bleeding or Inflammation: Safety has not been established for these patients.
Adverse Events: The most common adverse events with Auryxia were diarrhea (21%), nausea (11%), constipation (8%), vomiting (7%) and cough (6%). Gastrointestinal adverse reactions were the most common reason for discontinuing Auryxia (14%). Auryxia contains iron and may cause dark stools, which is considered normal with oral medications containing iron.
Drug Interactions: Doxycycline should be taken at least 1 hour before Auryxia. Ciprofloxacin should be taken at least 2 hours before or after Auryxia.
Forward Looking Statements
Some of the statements included in this press release, particularly those regarding the commercialization and ongoing clinical development of Auryxia and the submission of an sNDA to the
1Wolf M. Update on fibroblast growth factor 23 in chronic kidney disease. KidneyInt. 2012;82(7):737–747.
2David V, et al. Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production. Kidney Int. 2016;89(1):136–146.
3Isakova T, Xie H, Yang W, et al.
4David V, et al. Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production. Kidney Int. 2016;89(1):136–146. Wolf M. Update on fibroblast growth factor 23 in chronic kidney disease. KidneyInt. 2012;82(7):737–747.
KERYX BIOPHARMACEUTICALS CONTACTS:
Senior Vice President, Corporate Affairs
Senior Director, Investor Relations & Corporate Communications
Source: Keryx Biopharmaceuticals, Inc.