KERX Keryx Biopharmaceuticals, Inc. (delisted)

Keryx Biopharmaceuticals, Inc. (NASDAQ:KERX), a company focused on bringing innovative medicines to people with kidney disease, today announced two presentations of data on Auryxia® (ferric citrate) at the 2017 American Society of Nephrology (ASN) Annual Meeting being held October 31 - November 5, 2017 in New Orleans. The presentations are based on post-hoc analysis of the Phase 3 study of ferric citrate in adults with iron deficiency anemia and non-dialysis dependent chronic kidney disease (NDD-CKD). In an oral presentation, Geoffrey Block, M.D., described the effect of ferric citrate on fibroblast growth factor (FGF23), a phosphate-regulating hormone that is associated with chronic kidney disease progression1. Separately, a poster presentation showed the effect of ferric citrate on serum phosphorus in patients with normal and elevated baseline phosphorus levels.

In the U.S., Auryxia is FDA-approved as a phosphate binder indicated for the control of serum phosphorus levels in adult patients with chronic kidney disease on dialysis. Keryx is seeking to expand the indication for Auryxia to include the treatment of iron deficiency anemia in people with non-dialysis dependent chronic kidney disease. A supplemental new drug application is under review by the U.S. FDA, with a Prescription Drug User Fee Act (PDUFA) target action date of November 6, 2017.

“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 John Neylan, M.D., chief medical officer of Keryx Biopharmaceuticals. “The presentation of these data support our commitment to advancing the science of chronic kidney disease to improve the care of people living with this serious disease.”

“FGF23 is emerging as an important biomarker of chronic kidney disease,” said Geoffrey Block, M.D., director of clinical research at Denver Nephrology. “A potential oral treatment option for iron deficiency anemia in patients with non-dialysis dependent CKD, which also reduces FGF23, could be important in the management of CKD.” 

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 January 2017 in the Journal of the American Society of Nephrology (JASN), the results from the Phase 3 study demonstrated that patients treated with Auryxia (n=117) for 16-weeks achieved a statistically significant increase in hemoglobin and two other iron measurements, transferrin saturation (TSAT) and ferritin, compared to placebo (n=116). The mean reduction in serum phosphorus over 16 weeks in ferric citrate-treated patients was modest, but statistically significant compared with patients in the placebo group. In addition, the incidence of hypophosphatemia reported as an adverse event in ferric citrate-treated patients was low at <1 percent compared to 1.7 percent in the placebo group.

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

	Ferric Citrate		Placebo		p-value
Variables	Baseline(n=116, cFGF23, n=117 iFGF23)	Week 16(n=85 cFGF23, n=86 iFGF23)	Baseline(n=113, cFGF23, n=114 iFGF23)	Week 16(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%
i-FGF23(pg/mL) n=117	BL median	89.7	118.1	205.3	250.2	117.1	143.5
	16 wks median	85.0	102.2	152.0	156.6	101.4	113.0
	P-value*	0.340	0.004	0.012	0.031	<0.001	0.019
c-FGF23(RU/mL)n=116	BL median	266.0	330.5	415.8	576.8	427.4	297.8
	16 wks median	173.1	198.3	328.0	592.1	259.3	207.1
	p-value*	0.021	<0.001	0.027	0.297	<0.001	0.009
*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-value**	0.115	0.002	<0.001	0.032
** p-values are from a parameter t-test
BL P = baseline phosphorus level

About Auryxia® (ferric citrate) tabletsAuryxia (ferric citrate) was approved by the U.S. Food and Drug Administration on September 5, 2014 and is indicated in the U.S. for the control of serum phosphorus levels in adults with CKD on dialysis. The U.S. approval of Auryxia was based on data from the company's Phase 3 registration program in dialysis patients. In the Phase 3 clinical trials, Auryxia effectively reduced serum phosphorus levels to within the KDOQI guidelines range of 3.5 to 5.5 mg/dL. For more information about Auryxia and the U.S. full prescribing information, visit www.Auryxia.com.

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 FDA to expand the label of ferric citrate to include the treatment of IDA in adults with stage 3-5 NDD-CKD and the potential approval in this indication and the impact thereof on Keryx, may be forward-looking statements that involve a number of risks and uncertainties. For those statements, we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. Among the factors that could cause our actual results to differ materially are the following: whether we can increase adoption of Auryxia in patients with CKD on dialysis; whether we can maintain our operating expenses to projected levels while continuing our current clinical, regulatory and commercial activities; the risk that the FDA may not concur with our interpretation of our Phase 3 study results in NDD- CKD, supportive data, conduct of the studies, or any other part of our regulatory submission and could ultimately deny approval of ferric citrate for the treatment of IDA in adults with stage 3-5 NDD-CKD; the risk that if approved for use in NDD-CKD that we may not be able to successfully market Auryxia for use in this indication; our ability to continue to supply Auryxia to the market; and other risk factors identified from time to time in our reports filed with the Securities and Exchange Commission. Any forward looking statements set forth in this press release speak only as of the date of this press release. We do not undertake to update any of these forward looking statements to reflect events or circumstances that occur after the date hereof. This press release and prior releases are available at http://www.keryx.com. The information found on our website is not incorporated by reference into this press release and is included for reference purposes only.

About Keryx Biopharmaceuticals, Inc.Keryx Biopharmaceuticals, Inc., with headquarters in Boston, Massachusetts, is focused on the development and commercialization of innovative medicines that provide unique and meaningful advantages to people with kidney disease. The Keryx team consists of approximately 200 committed people working with passion to advance the care of people with this complex disease. In September 2014, the U.S. Food and Drug Administration approved Keryx’s first medicine, Auryxia® (ferric citrate) tablets. For more information about Keryx, please visit www.keryx.com.

References

1Wolf M. Update on fibroblast growth factor 23 in chronic kidney disease. Kidney Int. 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. Chronic Renal Insufficiency Cohort (CRIC) Study Group. Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA. 2011;305(23):2432–2439.Scialla JJ, Xie H, Rahman M, et al. Chronic Renal Insufficiency Cohort (CRIC) Study Investigators. Fibroblast growth factor-23 and cardiovascular events in CKD. J Am Soc Nephrol. 2014;25(2):349–360.

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. Kidney Int. 2012;82(7):737–747.

KERYX BIOPHARMACEUTICALS CONTACTS:Amy SullivanSenior Vice President, Corporate AffairsT: 617.466.3519amy.sullivan@keryx.com

Lora PikeSenior Director, Investor Relations & Corporate CommunicationsT: 617.466.3511lora.pike@keryx.com