Keryx Biopharmaceuticals Announces Multiple Scientific Presentations of Phase 3 Trial Results of Ferric Citrate for Iron Deficiency Anemia (IDA) in Non-Dialysis Dependent Chronic Kidney Disease (NDD-CKD)

• Pivotal Phase 3 data showed the potential of Ferric Citrate (Auryxia®) to treat IDA in adults with NDD-CKD
   
• Phase 3 trial results support supplemental new drug application (sNDA) seeking to expand Auryxia’s label

CHICAGO, Nov. 17, 2016 (GLOBE NEWSWIRE) -- Keryx Biopharmaceuticals, Inc. (Nasdaq:KERX), a biopharmaceutical company focused on bringing innovative medicines to people with renal disease, announced presentation of additional data from its pivotal Phase 3 study for iron deficiency anemia (IDA) and non-dialysis dependent chronic kidney disease (NDD-CKD) in four posters at the American Society of Nephrology’s 2016 Kidney Week taking place November 15-20 in Chicago. Data in the posters highlight an investigational use of ferric citrate as a potential oral treatment for adults with IDA and NDD-CKD. These results are a more detailed presentation of top line results announced in March 2016.

Ferric citrate (Auryxia®) is currently indicated in the U.S. as a phosphate binder for the control of serum phosphorus levels in patients with CKD on dialysis.

Taken together, data in the posters demonstrate that in the Phase 3 trial, the majority of patients treated with ferric citrate, 52.1 percent (61/117), achieved the primary endpoint of ≥1 g/dL increase in hemoglobin at any point during the 16-week efficacy period, 93.4 percent (57/61) of whom had a sustained treatment effect. Increases in hemoglobin in ferric-citrate treated patients were observed as early as one to two weeks after the start of treatment. Efficacy results were consistent across groups with different baseline characteristics. These results were achieved without the concomitant use of erythropoietin-stimulating agents (ESAs) or intravenous (IV) iron. Adverse events were generally similar between treatment arms and consistent with the safety profile described in the U.S. prescribing information for Auryxia, with gastrointestinal (GI) disorders as the most common adverse event. Serum phosphorus levels stayed within target ranges for CKD.

“I’m pleased to have been involved in this pivotal Phase 3 study of ferric citrate,” said Steven Fishbane, M.D., chief of nephrology for North Shore University Hospital and Long Island Jewish Medical Center. “The data presented today at Kidney Week continue to underscore ferric citrate’s ability to increase iron stores and hemoglobin in patients with CKD and IDA, and support its potential utilization in non-dialysis dependent chronic kidney disease, if approved by the FDA for this indication.”

“People with chronic kidney disease suffer from a range of complications, including two that are very common, hyperphosphatemia and iron deficiency anemia,” said John Neylan, M.D., chief medical officer of Keryx Biopharmaceuticals. “We are pleased to have the opportunity to further characterize the pivotal phase 3 trial results of ferric citrate’s investigational use in a scientific forum. These data support our goal to expand ferric citrate’s label and we look forward to submitting the sNDA for IDA in NDD-CKD patients to the FDA.”

About NDD-CKD, Iron Deficiency Anemia
Iron deficiency anemia is a common complication in patients with non-dialysis dependent chronic kidney disease (NDD-CKD), and the prevalence and severity of IDA increases as kidney disease progresses. It is estimated that there are approximately 1.6 million people living in the U.S. with stage 3-5 non-dialysis dependent chronic kidney disease and iron deficiency anemia⁽¹⁾_.  Efficacy and tolerability of current oral iron supplements are mixed. Intravenous (IV) iron administration is associated with important risks and burdens.

About the Pivotal Phase 3 Clinical Study
The pivotal Phase 3 study randomized 234 patients (233 patients received at least one starting dose of ferric citrate) at 32 clinical sites in the United States. NDD-CKD patients with hemoglobin levels between 9.0 mg/dL and 11.5 mg/dL and who were intolerant to or had inadequate response to oral iron supplements were randomized 1:1 (ferric citrate versus placebo), n=117 and n=116, respectively. Patients enrolled in the study were not allowed to receive any IV or oral iron, or ESAs during this study. The study had a 16-week, randomized, double-blind, placebo-controlled, efficacy period followed by an 8-week open-label safety extension period in which all patients remaining in the study, including the placebo group, received ferric citrate. During the 16-week efficacy period, ferric citrate was administered at a starting dose of three tablets per day with food and could be titrated every four weeks by an additional three tablets for up to a maximum of 12 tablets per day; the mean dose received in ferric citrate treated patients was 5 tablets per day. The primary endpoint was the proportion of patients achieving a ≥1 g/dL increase in hemoglobin at any point during the 16-week efficacy period.

Poster Presentations
Four posters presented during Kidney Week are related to the Phase 3 clinical trial.

• Effects of ferric citrate in adults with non-dialysis dependent chronic kidney disease and iron deficiency anemia: Phase 3 Clinical Trial, Stephen Fishbane, M.D., co-chair of the Phase 3 trial and division chief, kidney disease and hypertension at North Shore University Hospital/Long Island Jewish Medical Center
• Hemoglobin response to ferric citrate in subjects with non-dialysis dependent chronic kidney disease and iron deficiency anemia: Data from a Phase 3 clinical trial, Glenn Chertow, M.D., M.P.H., co-chair of the Phase 3 trial and professor of medicine and chief, division of nephrology at Stanford University School of Medicine;
• Effects of ferric citrate on parameters of mineral and bone metabolism in patients with non-dialysis dependent chronic kidney disease treated for iron deficiency anemia, Geoffrey Block, M.D. co-chair of the Phase 3 trial and director of clinical research at Denver Nephrology
• Predictors of hemoglobin response to ferric citrate in patients with non-dialysis dependent chronic kidney disease and iron deficiency anemia, Pablo Pergola, M.D., Ph.D., of Renal Associates in San Antonio, Texas.

Summary of Phase 3 trial data presented in four poster presentations
An analysis of the 16-week randomized efficacy period of the Phase 3 data study of ferric citrate (FC) dosed to improve hemoglobin levels showed that ferric citrate was well tolerated. 52.1 percent (61/117) of ferric citrate treated patients achieved the primary endpoint without the use of IV iron or ESA compared to 19.1 percent in the placebo group. Of the patients in the ferric citrate treatment group who achieved the primary endpoint, 93 percent (57/61) had a sustained treatment effect as defined by a mean change from baseline of ≥0.75 mg/dL over any 4-week time period provided that an increase of >1.0 g/dL had occurred during that 4-week period. Increases in hemoglobin were observed as early as one to two weeks after the start of treatment with ferric citrate. Additional analyses of patients at the end of the 16-week efficacy period were conducted and reported in the posters that showed:

• A mean relative change of ferric citrate versus placebo of 18.4 percent in TSAT and 170.3 ng/mL in ferritin, which are two measures of iron stores; iron deficiency anemia develops when a body’s iron stores are low.  
• Baseline characteristics, including severity of anemia, CKD stage, age, and gender, were not associated with hemoglobin response.
• Ferric citrate modestly improved markers of bone and mineral disease, including serum phosphate, serum parathyroid hormone (PTH) levels, and Fibroblast Growth Factor 23 (FGF 23) – a protein that is elevated in CKD and is associated with cardiovascular morbidity. Serum phosphorus levels decreased by 0.43 mg/dL in the ferric citrate group and by 0.22 g/dL in the placebo group. Adverse events of hypophosphatemia occurred in one patient receiving ferric citrate and three placebo patients. There were no discontinuations in the study due to hypophosphatemia. Phosphorus levels of < 2.0 mg/dL occurred infrequently during ferric citrate treatment – in two patients in the ferric citrate group during the 16 week randomized period and another patient in the safety extension phase. Phosphorus levels rapidly restored to normal levels with dose reduction, per protocol of the Phase 3 study.
• Patients who switched from placebo to ferric citrate during the 8-week, open label safety extension phase experienced therapeutic responses in hemoglobin, ferritin, TSAT, and serum phosphate similar to those initiating ferric citrate at the start of the trial. 86 patients from the ferric citrate group and 81 patients from the placebo group entered the extension period and, per protocol, started on the same ferric citrate dose of three tablets per day. Serious adverse events occurred in 3.5 percent of patients who continued on the FC group and 11.1 percent of patients who rolled over from the placebo group.
• Ferric citrate was well tolerated with up to 16 weeks of dosing. Adverse events were mild to moderate. The most common adverse events occurring in >5 percent of patients in either treatment group were diarrhea, constipation, discolored feces, nausea and abdominal pain. Rates of serious adverse events did not differ between ferric citrate and placebo treated groups. Serious adverse events occurred in 12.0 percent of the ferric citrate group and 11.2 percent in the place group. Overall, safety data were consistent with previously reported Phase 3 topline results and previous clinical experience with ferric citrate in the hemodialysis setting.

Use of ferric citrate in patients with NDD-CKD and IDA, as highlighted above, is investigational and has not been determined to be safe or efficacious.

¹McClellan et al. Curr Med Res Opin. 2004;20(9):1501-1510.

About Auryxia
Auryxia (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 patients 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.

Auryxia binds with dietary phosphate in the GI tract and precipitates as ferric phosphate. The unbound portion of Auryxia has been shown to increase serum iron parameters including ferritin and transferrin saturation (TSAT). Iron absorption from Auryxia may lead to excessive elevations in iron stores. Accordingly, physicians should assess and monitor iron parameters before starting and while on Auryxia, and may need to decrease or discontinue IV iron for these patients. The most common adverse events for Auryxia treated patients were gastrointestinal related, including diarrhea, nausea, vomiting and constipation. For more information about Auryxia and the U.S. full prescribing information, visit www.Auryxia.com.

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.

For Full Prescribing Information for Auryxia, please visit http://auryxia.com/important-safety-information/

Forward Looking Statements
Some of the statements included in this press release, particularly those regarding the commercialization and ongoing clinical development of Auryxia, 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; the risk that the FDA may not concur with our interpretation of our Phase 3 study results in non-dialysis dependent (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; 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, with headquarters in Boston, is focused on bringing innovative medicines to market for people with renal disease. In December 2014, the company launched its first FDA-approved medicine, Auryxia® (ferric citrate) in the United States. In January 2014, ferric citrate was approved for use in Japan, where it is being marketed as Riona® by Keryx's Japanese partner, Japan Tobacco Inc. and Torii Pharmaceutical Co. Ltd. In September 2015, the European Commission granted European market authorization for Fexeric® (ferric citrate coordination complex). For more information about Keryx, please visit www.keryx.com.

KERYX BIOPHARMACEUTICALS CONTACTS:
Amy Sullivan
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T: 617.466.3519
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Lora Pike
Senior Director, Investor Relations
T: 617.466.3511
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