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Keryx Biopharmaceuticals Announces Zerenex(TM) (ferric citrate coordination complex) Meets All Primary and Key Secondary



Keryx Biopharmaceuticals Announces Zerenex(TM) (ferric citrate coordination
complex) Meets All Primary and Key Secondary Endpoints in Phase 2 Study of
Non-Dialysis Dependent Chronic Kidney Disease Patients With Elevated Serum
Phosphorus and Iron Deficiency Anemia

Highly Statistically Significant Differences Observed in Serum Phosphorus,
TSAT, Ferritin, Hemoglobin and FGF-23 versus Placebo

Conference Call to Be Held Today, November 5, 2013, at 8:30 am Eastern Time

NEW YORK, Nov. 5, 2013 (GLOBE NEWSWIRE) -- Keryx Biopharmaceuticals, Inc.
(Nasdaq:KERX) today announced successful top-line results from its Phase 2
study of Zerenex™ (ferric citrate coordination complex) in non-dialysis
dependent chronic kidney disease (NDD-CKD) patients with elevated serum
phosphorus and iron deficiency anemia. In this study, Zerenex met both
co-primary endpoints, described below, demonstrating highly statistically
significant changes in serum phosphorus and transferrin saturation (TSAT)
versus placebo over the 12-week treatment period. In addition, Zerenex met the
key secondary endpoints of increasing ferritin and hemoglobin, and decreasing
fibroblast growth factor-23 (FGF-23) versus placebo. The Company plans to meet
with the Food and Drug Administration (FDA) to discuss these data with the
goal of defining a path forward towards obtaining a labeled indication for the
treatment of iron deficiency anemia in NDD-CKD patients.

The Co-Chairmen of the study were Geoffrey A. Block, MD, Director of Clinical
Research at Denver Nephrology; Glenn Chertow, MD, Chief, Division of
Nephrology and Professor of Medicine at Stanford University School of
Medicine; and Steven Fishbane, MD, Chief, Division of Nephrology, Vice
President of North Shore-LIJ Health System for Network Dialysis Services and
Director of Clinical Research at North Shore-LIJ Department of Medicine.

Study Design

This Phase 2 study was a multicenter, randomized, double-blind,
placebo-controlled clinical trial in subjects with stage 3 to 5 NDD-CKD, with
elevated serum phosphorus ≥4.0 mg/dL and iron deficiency anemia. The study
consisted of a 2-week washout period (for subjects on a phosphate binder at
screening) followed by a 12-week treatment period in which subjects were
randomized 1:1 to receive either Zerenex or placebo. One hundred forty-nine
(149) subjects were randomized into the study from 20 sites in the United
States.

The use of intravenous (IV) iron and erythropoiesis-stimulating agents (ESAs)
were not permitted within 8 weeks and 4 weeks prior to the study,
respectively, and not permitted during the course of the study. Oral iron
therapy was also not permitted during the course of the study.

Co-Primary and Key Secondary Endpoints

Zerenex met both co-primary and all key secondary endpoints with highly
statistically significant results.

The Intent-to Treat (ITT) group included 141 subjects, representing all
subjects who took at least one dose of Zerenex or placebo and provided at
least one post-baseline efficacy assessment.

The co-primary efficacy endpoints of this trial were the mean changes in serum
phosphorus and TSAT from baseline to the end of the 12-week treatment period
versus placebo in the ITT group.

Mean Serum Phosphorus (mg/dL)              Placebo          Zerenex
                                           (n=69)           (n=72)
Baseline                                   4.7              4.5
End of Treatment^1 (Week 12)               4.4              3.9
Treatment Difference p-value^2                              p < 0.001
^1 Last observation carried forward was used for missing data. 
^2 P-value is created via an ANCOVA model with treatment as the fixed effect
and baseline as the covariate.^ 
 

TSAT (%)                                   Placebo          Zerenex
                                           (n=69)           (n=72)
Baseline                                   21               22
End of Treatment^1 (Week 12)               20               32
Treatment Difference p-value^2                              p < 0.001
^1 Last observation carried forward was used for missing data. 
^2 P-value is created via an ANCOVA model with treatment as the fixed effect
and baseline as the covariate. 

The key secondary endpoints of the study were the mean changes in ferritin,
hemoglobin and FGF-23 from baseline to the end of the 12-week treatment period
versus placebo in the ITT group.

Mean Ferritin (ng/mL)                      Placebo          Zerenex
                                           (n=69)           (n=72)
Baseline                                   110              116
End of Treatment^1 (Week 12)               106              189
Treatment Difference p-value^2                              p < 0.001
^1 Last observation carried forward was used for missing data. 
^2 P-value is created via an ANCOVA model with treatment as the fixed effect
and baseline as the covariate.^ 
 

Mean Hemoglobin (g/dL)                     Placebo          Zerenex
                                           (n=69)           (n=72)
Baseline                                   10.6             10.5
End of Treatment^1 (Week 12)               10.4             11
Treatment Difference p-value^2                              p < 0.001
^1 Last observation carried forward was used for missing data. 
^2 P-value is created via an ANCOVA model with treatment as the fixed effect
and baseline as the covariate.^ 
 

Mean Intact FGF-23 (pg/mL)                 Placebo           Zerenex
                                           (n=60)            (n=63)
Baseline                                   263               319
End of Treatment^1 (Week 12)               293               200
Treatment Difference p-value^2                               P=0.017
^1 Last observation carried forward was used for missing data. Intact FGF-23
was assessed at baseline, Week 6 and Week 12.^ 
^2 P-value is created via an ANCOVA model with treatment as the fixed effect
and baseline as the covariate. 
 

Mean C-Terminal FGF-23 (pg/mL)             Placebo          Zerenex
                                           (n=60)           (n=63)
Baseline                                   511              468
End of Treatment^1 (Week 12)               579              316
Treatment Difference p-value^2                              p < 0.001
^1 Last observation carried forward was used for missing data. C-Terminal
FGF-23 was assessed at baseline, Week 6 and Week 12. 
^2  P-value is created via an ANCOVA model with treatment as the fixed effect
and baseline as the covariate.

Zerenex was also highly statistically significant in its mean changes at Week
12 versus baseline for all the above-mentioned co-primary and key secondary
endpoints.

Treatment Failures

Patients were discontinued from the study if they had hemoglobin measurements
< 9.0 g/dL on two consecutive visits or serum phosphorus measurements ≥6.0
mg/dL on two consecutive visits following randomization. Treatment Failures in
the study were as follows: 

Treatment Failures (n)       Placebo Zerenex
                             (n)     (n)
Hemoglobin < 9.0 g/dL        9       1
Serum Phosphorus ≥ 6.0 mg/dL 2       0

Safety and Tolerability Profile

The safety population in the study included all randomized patients who took
at least one dose of study drug. Zerenex appeared to be safe and
well-tolerated in this Phase 2 study, with discontinuation rates of 19% and
32% in the Zerenex and placebo groups, respectively, including Treatment
Failures. There were no study discontinuations due to hypophosphatemia in the
study. 

Serious adverse events occurred in six Zerenex subjects (8%) versus ten
placebo subjects (14%). Two deaths were recorded in the study, both from the
placebo group. There were no clinically meaningful or statistically
significant differences in serum calcium levels and liver enzymes as measured
by alanine transaminase (ALT) and aspartate transaminase (AST). 

The full efficacy and safety data from the study is expected to be presented
at a future medical conference.

Ron Bentsur, Chief Executive Officer of Keryx, stated, "We are very excited
about these top-line data, which demonstrate that Zerenex can potentially
treat elevated phosphorus and also iron deficiency anemia in CKD patients
without the need for IV iron and ESAs." Mr. Bentsur continued, "Zerenex has
the potential to capitalize on this largely underserved patient population of
over 1.5 million stages 3 to 5 non-dialysis dependent CKD patients, in the
U.S. alone, who suffer from iron deficiency anemia by potentially becoming the
first oral iron drug effective at treating this indication, with the added
benefit of providing serum phosphorus control." 

Dr. Geoffrey Block, Co-Chairman of the study, commented, "I enrolled a large
number of patients into this study and I am thrilled by these data. Zerenex's
robust effect to reduce serum phosphorus in this study population is
clinically quite important given that serum phosphorus levels greater than 4.0
mg/dL in patients with CKD have been associated with vascular calcification,
progression of CKD and increased mortality.  Being able to combine the
phosphate lowering effect with the magnitude of the observed effects of
Zerenex on hemoglobin and iron storage parameters, with no background use of
iron and ESAs, as well as the profound reduction observed in FGF-23, I believe
that Zerenex can potentially change practice patterns in CKD anemia
management."

Dr. Glenn Chertow, Co-Chairman of the study, commented, "It is exciting to
observe these encouraging top-line results which demonstrate that Zerenex
could have several desired effects in non-dialysis dependent CKD.  I look
forward to the continued development of Zerenex in this indication and
possibly additional iron deficiency anemia indications outside of CKD."

Dr. Steve Fishbane, Co-Chairman of the study, commented, "I have focused much
of my career as a nephrologist on anemia management. Simply put, the data
presented today demonstrate that Zerenex, an oral iron drug that increases
iron stores and mitigates the need for IV iron and ESAs, has the potential to
change the treatment paradigm for iron deficiency anemia in CKD. An oral drug
producing these results suggests the potential for a more efficient and safer
approach to anemia management than currently offered by today's intravenous
therapies."

The Company's New Drug Application (NDA) for the use of Zerenex for the
treatment of hyperphosphatemia in chronic kidney disease patients on dialysis
is currently under review by the FDA with an assigned Prescription Drug User
Fee Act (PDUFA) goal date of June 7, 2014.

Keryx is grateful for the dedication and support of the Co-Chairmen and the
clinical investigators of this study. Keryx also thanks Dr. Julia Lewis and
the Collaborative Study Group for their invaluable leadership of the Zerenex
dialysis development program.

Keryx holds a worldwide license (except for certain Asian Pacific countries)
to Zerenex (ferric citrate coordination complex) from Panion & BF Biotech,
Inc. The Japanese rights are sublicensed by Keryx to Japan Tobacco Inc. and
Torii Pharmaceutical Co., Ltd.

Conference Call Information

Keryx will host a conference call today, November 5, 2013 at 8:30 a.m. Eastern
Time to present the top-line results from this Phase 2 study for Zerenex. The
conference call can be accessed by dialing 1-877-869-3847 (U.S.),
1-201-689-8261 (outside the U.S.), call-in ID: KERYX. The rebroadcast of the
conference call will be available for replay at http://www.keryx.com, for a
period of 15 days after the call.

About Non-Dialysis Dependent Chronic Kidney Disease and Iron Deficiency Anemia

It is estimated that approximately 10 to 15% of the U.S. adult population is
affected by chronic kidney disease (CKD), a condition generally characterized
by greater than 50% reduction of normal kidney function. In addition, elevated
levels of serum phosphorus become more prevalent in stages 3 to 5 non-dialysis
dependent CKD (NDD-CKD) patients. Several studies have shown that higher serum
phosphorus concentrations may be associated with increased mortality and
morbidity in CKD, however, no phosphate binders are currently FDA approved for
NDD-CKD.

Iron deficiency anemia, which develops early in the course of CKD and worsens
with disease progression, is extremely prevalent in the NDD-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. Based on data contained in a 2009 publication in the
Journal of the American Society of Nephrology, it is estimated that over 1.5
million adults with stages 3 to 5 NDD-CKD in the United States alone are
afflicted with iron deficiency anemia. To combat this anemia, iron replacement
therapy is essential to increase iron stores, such as ferritin and TSAT
levels, and raise hemoglobin levels. Currently available oral iron supplements
are associated with limited efficacy and dose-limiting tolerability issues. No
oral iron agents are currently FDA approved to treat iron deficiency anemia in
NDD-CKD. Erythropoiesis stimulating agents (ESAs) and intravenous (IV) iron
are not frequently administered in NDD-CKD due to both the FDA warning label
of potential cardiovascular risk for ESAs in NDD-CKD and logistical
complications associated with administering IV medicines in office settings
which lack the necessary facilities, such as emergency equipment and/or
emergency medical access. Consequently, the NDD-CKD patient population remains
underserved.

About Fibroblast Growth Factor-23 (FGF-23)

Fibroblast growth factor-23 (FGF-23) is a hormone that is believed to be
associated with bone and mineral homeostasis in CKD patients and may also have
a role in vascular calcification.  Recent studies suggest that increased
FGF-23 is associated with mortality, left ventricular hypertrophy, endothelial
dysfunction and progression of CKD and that iron deficiency anemia is
associated with increased FGF-23. 

About Keryx Biopharmaceuticals, Inc.

Keryx Biopharmaceuticals is focused on the acquisition, development and
commercialization of medically important pharmaceutical products for the
treatment of renal disease. Keryx is developing Zerenex (ferric citrate
coordination complex), an oral, ferric iron-based compound that has the
capacity to bind to phosphate and form non-absorbable complexes. Keryx has
completed a U.S.-based Phase 3 clinical program for Zerenex for the treatment
of hyperphosphatemia (elevated phosphate levels) in patients with chronic
kidney disease on dialysis, conducted pursuant to a Special Protocol
Assessment (SPA) agreement with the Food and Drug Administration (FDA). The
Company's New Drug Application (NDA) is currently under review by the FDA with
an assigned Prescription Drug User Fee Act (PDUFA) goal date of June 7, 2014.
 The Marketing Authorization Application filing with the European Medicines
Agency (EMA) is pending submission. The Company is also developing Zerenex in
the U.S. for the management of elevated phosphorus and iron deficiency anemia
in patients with stages 3 to 5 non-dialysis dependent chronic kidney disease.
In addition, Keryx's Japanese partner, Japan Tobacco Inc. and Torii
Pharmaceutical Co., Ltd. has filed its New Drug Application for marketing
approval of ferric citrate in Japan for the treatment of hyperphosphatemia in
patients with chronic kidney disease. Keryx is headquartered in New York City.

Forward-Looking Statements

Some of the statements included in this press release, particularly those
relating to the results of clinical trials, the clinical benefits to be
derived from Zerenex (ferric citrate coordination complex), regulatory
submissions and the timing of any such review, approvals, the commercial
opportunity and competitive positioning, and any business prospects for
Zerenex, 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: top-line results are based on
a preliminary analysis of then available data (both safety and efficacy) and
there is the risk that such findings and conclusions could change following a
more comprehensive review of the data; the FDA may not provide us with a
regulatory path forward in NDD-CKD that is acceptable to us; acceptance of the
NDA filing represents only a preliminary evaluation of the application and is
not indicative of deficiencies that may be identified during the FDA's review;
a PDUFA goal date is subject to change and does not guarantee that the review
of the NDA will be completed on a timely basis; the risk that the FDA, EMA,
and/or the Japanese Ministry of Health, Labour and Welfare ultimately deny
approval of the U.S. NDA, MAA and/or Japanese NDA, respectively; the risk that
SPAs are not a guarantee that the FDA will ultimately approve a product
candidate following filing acceptance; whether the FDA and EMA will concur
with our interpretation of our Phase 3 study results, supportive data, or the
conduct of the studies; whether, Zerenex, if approved, will be successfully
launched and marketed; 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.

CONTACT: Lauren Fischer
         Director - Investor Relations
         Keryx Biopharmaceuticals, Inc.
         Tel: 212.531.5965
         E-mail: lfischer@keryx.com

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