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Keryx Biopharmaceuticals, Inc.

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PLEASE SCROLL DOWN TO THE RESULTS SECTION (below) TO SEE THE OUTCOME OF THIS EVENT.

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John F. Neylan, MD, Chief Medical Officer, commented on the phase-III trial for Auryxia in IDA. He stated, "Our clinical development team has been working diligently to conclude the phase-III study, evaluating ferric citrate for the treatment of iron deficiency anemia in patients with pre-dialysis CKD. As planned the last patient’s last visit occurred in January and we are now finalizing all of the data for the 234 patients enrolled in the trial. We remain blinded to these data while this important work continues. Provision of a new oral therapy for iron deficiency anemia in the pre-dialysis CKD patient setting has the potential to dramatically change nephrology practice. As we stated earlier this year at the JPMorgan Conference, new market research has revealed a large and readily addressable patient population. I will recap, there are approximately 1.7 million people in the U.S. alone with stages three through five CKD, who are under the care of a nephrologist."

He went on to say, "Turning quickly to our pivotal phase-III study, let me provide a high level overview of the studies designed and the patients who consented to participate. Slide 19 summarizes the design. The 24-week study includes 234 patients, all of whom have failed prior oral iron treatment. The primary endpoint is the proportion of patients who achieve a 1 gram or greater increase in hemoglobin at anytime during the first 16 weeks of the study. The study is at least 90% powered to detect a statistically significant difference in the treatment arm response compared to placebo. If the trial is successful, we plan to submit a regulatory application for FDA approval in the third quarter of this year and submit data for presentation at the ASN Conference taking place in the fourth quarter."
Source: Q4 2015 earnings conference call 2/25/16.

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A Phase 3 Study of KRX-0502 (Ferric Citrate) for the Treatment of Iron Deficiency Anemia in Adult Subjects With Non-Dialysis Dependent Chronic Kidney Disease
Enrollment: 234
Study Start Date: September 2014
Study Completion Date: January 2016
Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
more
Source: clinical trials.gov. https://clinicaltrials.gov/ct2/show/NCT02268994?term=keryx&cond=Iron&pha...

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Compound/DeviceSpecialtyIndicationCompound ClassTarget
Zerenex IDAHematologyAnemia (Iron deficiency)Iron replacement therapeuticRed blood cells

Mechanism of action: Zerenex, a SM, reduces serum phosphate levels by oral administration of an inorganic, iron-based compound that has the capacity to bind to phosphorous and form non-absorbable complexes.

Phase of Development: III

Event Type: Data: Phase III trial results

Dates: 2016-04-01 - 2016-06-30

Results:

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KERYX BIOPHARMACEUTICALS ANNOUNCES POSITIVE TOP-LINE RESULTS FROM PIVOTAL PHASE 3 STUDY OF FERRIC CITRATE FOR THE TREATMENT OF IRON DEFICIENCY ANEMIA IN ADULTS WITH NON-DIALYSIS DEPENDENT CHRONIC KIDNEY DISEASE
Registration trial demonstrated statistically significant differences versus placebo for the primary and all pre-specified secondary endpoints
Majority of patients in the ferric citrate group (52 percent) achieved a 1 g/dL increase in hemoglobin vs. 19 percent in the placebo group
Safety profile consistent with previously reported clinical studies
Data support Keryx’s plan to submit a supplemental new drug application (sNDA) in the third quarter of 2016 seeking to expand ferric citrate’s indication
Conference call to be held today at 8:00 a.m. ET

BOSTON, March 29, 2016 (GLOBE NEWSWIRE) -- Keryx Biopharmaceuticals, Inc. (Nasdaq:KERX), a biopharmaceutical company focused on bringing innovative medicines to market for people with renal disease, today announced positive top-line results for its pivotal 24-week Phase 3 study of ferric citrate, an oral, iron-based medicine in development for the treatment of iron deficiency anemia (IDA) in adults with stage 3-5 non-dialysis dependent chronic kidney disease (NDD CKD). The study met its primary endpoint and all pre-specified secondary endpoints with statistical significance.

Iron deficiency anemia is a common complication of 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. If ferric citrate is approved for the treatment of iron deficiency anemia in stage 3 – 5 NDD CKD patients, it would be the only FDA-approved iron treatment in a tablet form available to these patients.

The Phase 3 study compared treatment with ferric citrate to placebo in 234 patients who previously had not adequately responded to or tolerated current oral iron therapies. The study achieved the primary endpoint with 52 percent (61/117) of patients who received ferric citrate achieving a 1g/dL or greater rise in hemoglobin at any time point during the 16-week randomized efficacy period, compared to 19 percent (22/115) in the placebo group (p<0.001), a clinically meaningful and statistically significant improvement. Two patients in the placebo group discontinued the study and were not included in the efficacy analysis – one discontinued after randomization prior to receiving placebo, one discontinued after taking a dose of placebo but before having laboratory values drawn. Statistically significant differences in all pre-specified secondary efficacy endpoints were also observed. During the full 24 weeks of the study, ferric citrate was generally well tolerated and adverse events were consistent with its known safety profile, with diarrhea reported as the most common adverse event.

“These Phase 3 results demonstrate that ferric citrate can effectively raise hemoglobin levels in stage 3 – 5 non-dialysis dependent chronic kidney disease patients, with effects observed as early as two weeks post-treatment initiation,” said John Neylan, M.D., chief medical officer of Keryx Biopharmaceuticals. “Based on these results, we plan to submit an sNDA to the FDA in the third quarter, seeking to expand the label for ferric citrate to include the treatment of iron deficiency anemia in people with stage 3 – 5 NDD CKD. We believe that the ability to treat iron deficiency anemia, managing hemoglobin and iron levels, could have an important effect on the way kidney specialists treat these patients.”

About the Phase 3 Registration Study
The pivotal Phase 3 study enrolled 234 patients who previously had not adequately responded to or tolerated oral iron therapies at 32 clinical sites in the United States. Patients were randomized 1:1 (ferric citrate versus placebo). Patients enrolled in this study were not allowed to receive any intravenous (IV) or oral iron, or erythropoiesis-stimulating agents (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 or greater increase in hemoglobin at any point during the 16-week efficacy period. Baseline laboratory values were similar between the treatment arms.

Baseline laboratory values: Ferric Citrate (FC)
(n=117) Placebo (P)
(n=115)
Hemoglobin (g/dL) 10.4 10.4
TSAT (%) 20.2 19.6
Ferritin (ng/mL) 85.9 81.7
Serum phosphate (mg/dL) 4.2 4.1

The study’s chairmen are Geoffrey Block, M.D., director of clinical research at Denver Nephrology; Glenn Chertow, M.D., professor of medicine and chief, division of nephrology at Stanford University School of Medicine; and Steven Fishbane, M.D., division chief, kidney disease and hypertension at North Shore University Hospital/Long Island Jewish Medical Center.

Efficacy and safety analyses were performed on an intent-to-treat population and included all enrolled patients who received at least one dose of ferric citrate or placebo and one post-treatment laboratory assessment. The analysis also used a sequential gatekeeping strategy for statistical testing of the secondary endpoints.

Top-line Efficacy Results:

Primary endpoint: Ferric Citrate (FC)
(n=117) Placebo (P)
(n=115) P-value
Proportion of patients achieving an increase in hemoglobin of > 1.0 g/dL at any time point during efficacy period* (%) 52.1 19.1 <0.001
Secondary endpoints:
Mean change in hemoglobin (g/dL) 0.75 -0.08 <0.001
Mean change in TSAT (%) 17.8 -0.6 <0.001
Mean change in ferritin (ng/mL) 162.5 -7.7 <0.001
Proportion of patients with a durable response during the efficacy period (%)** 48.7 14.8 <0.001
Mean change in serum phosphate (mg/dL) -0.43 -0.22 0.02

* Efficacy period defined as the 16-week randomized, double-blind, placebo controlled period
** Sustained treatment effect on hemoglobin was defined as a mean change from baseline ≥0.75 g/dL over any 4-week time period during the efficacy period, provided that an increase of at least 1.0 g/dL had occurred during that 4-week period.

Top-line Safety Results:
The safety analysis demonstrated that ferric citrate was generally well tolerated in adults with stage 3-5 NDD CKD. Specifically, the results showed:

During the efficacy period, the majority of adverse events reported were mild to moderate, with the most common being diarrhea (20.5% FC; 16.4% P), constipation (18.8% FC; 12.9% P), discolored feces (14.5% FC; 0% P), and nausea (11.1% FC; 2.6%P). During the efficacy period, hypophosphatemia was reported as an adverse event in four patients, one patient in the ferric citrate arm and three patients in the placebo arm.
During the efficacy period, 26 percent (31/117) of ferric citrate-treated patients and 30 percent (35/116) of those receiving placebo discontinued treatment. Of the patients who discontinued, 12 patients treated with ferric citrate discontinued due to an adverse event, compared to 10 patients who received placebo.
During the efficacy period, the rate of serious adverse events was balanced between the ferric citrate and placebo treatment groups, at 12 percent and 10 percent, respectively. None of the serious adverse events were deemed drug related.
During the course of the study, there were two deaths reported, both in patients receiving ferric citrate; neither of which were related to study drug.

The company plans to submit detailed Phase 3 results for presentation at a premier kidney disease medical meeting taking place in the fourth quarter of 2016.

About Non-Dialysis Dependent Chronic Kidney Disease and Iron Deficiency Anemia
It is estimated that approximately one in 10 U.S. adults are affected by chronic kidney disease (CKD), which has no cure. Treatment today consists of measures to help control signs and symptoms, reduce the impact of many complications to make a person more comfortable and slow disease progression.

Iron deficiency anemia is one of the most common complications of chronic kidney disease. IDA develops early in the course of CKD and worsens with disease progression, is extremely prevalent in the non-dialysis dependent CKD population and is associated with fatigue, lethargy, decreased quality of life and is also believed to be associated with cardiovascular complications, hospitalizations, and increased mortality. There are five stages of CKD; in stages 1 and 2 people are typically under the care of a primary care physician and have a mild loss of kidney function. Typically, as people progress to stage 3 hemoglobin levels begin to fall, the patient experiences moderate to severe loss of kidney function and is generally referred to a nephrologist. Stage 4 is characterized as advanced disease with multiple complications. Stage 5 is considered kidney failure and the stage in which a patient would initiate dialysis. It is estimated that approximately 1.6 million adults with stage 3-5 CKD in the U.S. alone are also afflicted with iron deficiency anemia. Currently available oral iron supplements are associated with limited efficacy and dose-limiting tolerability issues. No oral iron medicines are currently FDA approved to treat iron deficiency anemia in non-dialysis dependent CKD patients, and the NDD-CKD patient population remains underserved.

Conference Call Information
Keryx will host an investor conference call today, March 29, 2016, at 8:00 a.m. ET to discuss the phase 3 topline results. In order to participate in the conference call, please call 1-(888) 396-2320 (U.S.), 1-(774) 264-7560 (outside the U.S.), call-in ID: 80960520. The call will also be webcast which will be accessible at http://edge.media-server.com/m/p/c55hde32 or through the Investors section of the company's website at www.keryx.com. The audio replay will be available at http://www.keryx.com for a period of 30 days after the call.
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Source: press release, 3/29/16. http://investors.keryx.com/phoenix.zhtml?c=122201&p=irol-newsArticle&ID=...

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