Keryx Biopharmaceuticals Announces Zerenex™ (ferric citrate) Meets Primary and All Key Secondary Endpoints in Phase 3 Long

Keryx Biopharmaceuticals Announces Zerenex™ (ferric citrate) Meets Primary and
  All Key Secondary Endpoints in Phase 3 Long-Term Study as a Treatment for
      Hyperphosphatemia in End-Stage Renal Disease Patients on Dialysis

Zerenex Significantly Increases Iron Storage Parameters and Decreases Need for
Intravenous Iron and Erythropoiesis-Stimulating Agents Versus Active Control

U.S. and European New Drug Application Submissions Anticipated in Second
Quarter 2013

Conference Call to Be Held Today, Monday, January 28, 2013, at 8:00 am Eastern
Time

PR Newswire

NEW YORK, Jan. 28, 2013

NEW YORK, Jan.28, 2013 /PRNewswire/ --Keryx Biopharmaceuticals, Inc.
(NASDAQ: KERX) today announced successful top-line results from the long-term
Phase 3 study of Zerenex™ (ferric citrate), the Company's ferric iron-based
phosphate binder drug candidate, for the treatment of elevated serum
phosphorus levels, or hyperphosphatemia, in patients with end-stage renal
disease (ESRD) on dialysis. In this study, Zerenex met the study's primary
endpoint, described below, demonstrating a highly statistically significant
change in serum phosphorus versus placebo over the four-week Efficacy
Assessment Period of the study. In addition, Zerenex met the key secondary
endpoints of increasing ferritin and transferrin saturation (TSAT) and
reducing the use of intravenous (IV) iron and erythropoiesis-stimulating
agents (ESAs) versus the active control over the 52-week Safety Assessment
Period of the study. This long-term study was the final component of the
Company's Phase 3 registration program, which was conducted pursuant to a
Special Protocol Assessment (SPA) with the Food and Drug Administration (FDA).
In April 2011, the Company reported the positive final dataset from the
short-term study component of this Phase 3 registration program. The Company
expects to submit a New Drug Application (NDA) with the FDA and a Marketing
Authorization Application (MAA) with the European Medicines Agency (EMA) for
Zerenex in the second quarter of 2013.

Study Design

This Phase 3 long-term study was a multicenter, randomized, open-label, safety
and efficacy clinical trial in 441 ESRD patients on hemodialysis or peritoneal
dialysis. The study consisted of a 2-week washout period followed by a 52-week
Safety Assessment Period in which subjects were randomized 2:1 to receive
either Zerenex or an active control (Renvela^® [sevelamer carbonate] and/or
Phoslo^® [calcium acetate]). The 52-week Safety Assessment Period was followed
by a 4-week Efficacy Assessment Period. During the Efficacy Assessment Period,
only those subjects randomized to treatment with Zerenex during the Safety
Assessment Period were randomized in a 1:1 ratio to either continue treatment
with Zerenex or switch to placebo for a 4-week treatment period. Subjects were
titrated during the study to achieve serum phosphorus levels that ranged
between 3.5 to 5.5 mg/dL.

The primary objectives of this study were to determine the long-term safety of
KRX-0502 (ferric citrate) in subjects with ESRD undergoing either hemodialysis
or peritoneal dialysis, and the efficacy of Zerenex following 52 weeks of
treatment in a four-week, randomized, open-label, placebo-controlled Efficacy
Assessment Period. Zerenex was administered using a 1 gram oral caplet
formulation.

Oral iron therapy was not permitted during the course of the study. IV iron
therapy was not permitted if a subject's serum ferritin level was greater than
1,000 ng/mL or the transferrin saturation (TSAT) was greater than 30%. The use
of ESAs was at the physician's discretion.

Primary Efficacy Endpoint

The primary efficacy endpoint of this trial was the mean change in serum
phosphorus from baseline (Week 52) to end of the four-week Efficacy Assessment
Period (Week 56) versus placebo in the Intent-to-Treat (ITT) group. The ITT
group included 183 subjects, representing all subjects who took at least one
dose of Zerenex or placebo in the Efficacy Assessment Period and provided at
least one post-baseline efficacy assessment.

Zerenex met the primary efficacy endpoint with a highly statistically
significant result (p<0.0001).

Mean Serum Phosphorus (mg/dL)                     Placebo Zerenex

                                                 (n=91)  (n=92)
Baseline (Week 52)                                5.3     5.2
End of Treatment^1 (Week 56)                      7.2     4.9
Change from Baseline at Week 56                   1.9     -0.3
Least Squares (LS) Mean Difference from Placebo^2          -2.3

p-value^2                                                 p<0.0001

^1 Last observation carried forward was used for missing data.
^2The LS Mean treatment difference and p-value is created via an ANCOVA
model with treatment as the fixed effect and baseline as the covariate.

Key Secondary Efficacy Endpoints Related to Serum Phosphorus

During the 52-week Safety Assessment Period, Zerenex maintained serum
phosphorus in the normal range, with highly statistically significant changes
in mean serum phosphorus concentration at Weeks 12, 24, 36, 48, and 52 as
compared to baseline (Day 0).

                              Week

n=277                  Baseline 12      24      36      48      52
Zerenex Mean Serum
                       7.4      5.4     5.2     5.2     5.3     5.3
Phosphorus (mg/dL)^1
Change from Baseline            -2.0    -2.2    -2.2    -2.1    -2.1
% Change from Baseline          -27.0%  -29.7%  -29.7%  -28.4%  -28.4%
p-value                         <0.0001 <0.0001 <0.0001 <0.0001 <0.0001

^1Last observation carried forward was used for missing data.

In addition, as agreed to with the European Medicines Agency (EMA), the
treatment difference between Zerenex and Renvela^® (sevelamer carbonate) at
Week 12 of the Safety Assessment Period in terms of change from baseline (Day
0) in serum phosphorus was analyzed. Zerenex successfully achieved the
non-inferiority endpoint versus Renvela^®.

Key Secondary Efficacy Endpoints Related to Iron

The objectives of the key iron-related secondary endpoints, which were all
pre-specified in the statistical analysis plan, were to corroborate prior data
which suggested that Zerenex may increase iron storage parameters and reduce
the need for IV iron and/or ESAs. Zerenex met all the key secondary efficacy
endpoints related to iron with statistically significant treatment differences
versus the active control group (Renvela^® [sevelamer carbonate] and/or
Phoslo^® [calcium acetate]), as follows:

Mean Change in Ferritin

Zerenex demonstrated a statistically significant treatment difference versus
the active control group in mean change in serum ferritin from baseline (Day
0) to Week 52.

Mean Ferritin (ng/mL)^1              Active Controls             Zerenex

                                    (n=134)                     (n=249)
Baseline (Day 0)                     616                         595
Week 12                              657                         751
Week 24                              658                         847
Week 36                              636                         863
Week 48                              627                         882
Week 52                              625                         897
Change from Baseline at Week 52       9  302

% Change from Baseline               1.5%     50.8%
LS Mean Difference from Active                                   
Control Group
at Week 52^2                                                     286
p-value^2                                                        p<0.0001

^1 Last observation carried forward was used for missing data.
^2The LS Mean treatment difference and p-value is created via an ANCOVA
model with treatment as the fixed effect and baseline as the covariate.

Mean Change in TSAT

Zerenex demonstrated a statistically significant treatment difference versus
the active control group in mean change in TSAT from baseline (Day 0) to Week
52.

Mean TSAT (%)^1                     Active Controls             Zerenex

                                   (n=131)                     (n=244)
Baseline (Day 0)                    31                          31
Week 12                             31                          40
Week 24                             32                          40
Week 36                             30                          40
Week 48                             29                          41
Week 52                             30                          39
Change from Baseline at Week 52      -1  8

% Change from Baseline               -3.2%     25.8%
LS Mean Difference from Active                                  
Control Group
at Week 52^2                                                    10
p-value^2                                                       p<0.0001

^1 Last observation carried forward was used for missing data.
^2The LS Mean treatment difference and p-value is created via an ANCOVA
model with treatment as the fixed effect and baseline as the covariate.

Cumulative IV iron Use

Each subject's average cumulative IV iron intake was calculated over the
52-week Safety Assessment Period. The ITT consisted of 278 subjects and 138
subjects for the Zerenex and active control groups, respectively. Zerenex
demonstrated a 51.6% decrease in median IV iron intake as compared to the
active control group (p<0.0001).

Cumulative Erythropoiesis-Stimulating Agent (ESA) Use

Each subject's average cumulative ESA intake was calculated over the 52-week
Safety Assessment Period. The ITT consisted of 280 subjects and 141 subjects
for the Zerenex and active control groups, respectively. Zerenex demonstrated
a 27.1% decrease in median ESA intake as compared to the active control group
(p=0.0322).

Mean Change in Hemoglobin

Zerenex demonstrated a statistically significant treatment difference versus
the active control group in mean change in hemoglobin from baseline (Day 0) to
Week 52.

Mean Hemoglobin (g/dL)^1                     Active Controls Zerenex

                                            (n=130)         (n=244)
Baseline (Day 0)                             11.7            11.6
Week 52                                      11.1            11.4
Change from Baseline at Week 52              -0.6            -0.2
LS Mean Difference from Active Control Group                 
at Week 52^2
                                                             0.4
p-value^2                                                    p=0.0105

^1 Last observation carried forward was used for missing data.

^2 The LS Mean treatment difference and p-value is created via an ANCOVA
model with treatment as the fixed effect and baseline as the covariate.

Safety and Tolerability Profile

For reference, subjects previously intolerant to Renvela^® (sevelamer
carbonate) and/or Phoslo^® (calcium acetate) were ineligible to participate in
this study. Consistent with previous studies, Zerenex appeared safe and well
tolerated in this study. Based on an analysis of safety data, the side-effect
profile of Zerenex and the Active Control group appeared similar, with the
most common adverse events gastrointestinal-related. The overall rate of
gastrointestinal-related adverse events, excluding feces discoloration which
is an asymptomatic Zerenex side effect, were 39% Zerenex vs. 44% Active
Control. The most common gastrointestinal adverse events were: diarrhea,
including soft stools (27% Zerenex vs. 14% Active Control), nausea (14%
Zerenex vs. 14% Active Control), vomiting (9% Zerenex vs. 13% Active Control)
and constipation (8% Zerenex vs. 5% Active Control). Adverse events were
generally characterized as mild to moderate in nature.

The overall serious adverse event rates in the study were 34% Zerenex vs. 43%
Active Control. Importantly, there were no clinically meaningful or
statistically significant differences between Zerenex and the active control
group 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.

Dr. Julia Lewis, Professor of Medicine, Department of Nephrology, Vanderbilt
University School of Medicine, member of the Executive Committee of the
Collaborative Study Group and Study Chair of the Zerenex Phase 3 registration
program, commented, "We are very excited by the results announced today. The
data from this study confirm that Zerenex is a safe and effective phosphate
binder with the added benefit of improving patients' iron levels while
utilizing significantly less IV iron and ESAs. There is a clear need for
viable alternatives to the marketed phosphate binders, and Zerenex can play a
major role by not only providing adequate phosphate binding, but also
providing additional benefits."

Ron Bentsur, Chief Executive Officer of Keryx, stated, "We are thrilled by the
robust outcome of this pivotal study for Zerenex, particularly with the
magnitude of the drug's effect on iron and anemia parameters, which should
prominently differentiate Zerenex versus all the currently marketed phosphate
binders. We believe that the ability to treat hyperphosphatemia, while also
increasing iron storage parameters and reducing the need for IV iron and ESAs,
sets a new paradigm for how a phosphate binder can be used to treat patients
with end-stage renal disease on dialysis. We believe that these data position
Zerenex to potentially become market leader in the phosphate binder market."
Mr. Bentsur continued, "We sincerely thank the study investigators and
coordinators, and are particularly grateful to the Collaborative Study Group
for their expertise, guidance and dedication to the clinical development of
Zerenex."

Zerenex is also in Phase 2 development in the U.S. for the management of
phosphorus and iron deficiency in anemic patients with Stage 3 to 5
non-dialysis dependent chronic kidney disease.

Keryx holds a worldwide license (except for certain Asian Pacific countries)
to Zerenex (ferric citrate) from Panion & BF Biotech, Inc. The Japanese rights
are sublicensed by Keryx to Japan Tobacco Inc. (JT) and Torii Pharmaceutical
Co., Ltd. (Torii). On January 7, 2013, JT announced the filing of its NDA
with the Japanese Ministry of Health, Labour and Welfare for marketing
approval of ferric citrate in Japan for the treatment of hyperphosphatemia in
patients with chronic kidney disease (CKD). The NDA filing is supported by
efficacy and safety data from several successfully completed Phase 3 studies
in CKD patients with hyperphosphatemia in Japan.

Conference Call Information

Keryx will host a conference call today, January 28, 2013 at 8:00 a.m. Eastern
Time to present the top-line results from this long-term Phase 3 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 Special Protocol Assessments

The Special Protocol Assessment (SPA) process is a procedure by which the FDA
provides official evaluation and written guidance on the design and size of
proposed protocols that are intended to form the basis for a new drug
application. Final marketing approval depends on the efficacy and safety
results, including the adverse event profile, and an evaluation of the
benefit/risk of treatment demonstrated in the Phase 3 clinical program. The
SPA agreement may only be changed through a written agreement between the
sponsor and the FDA, or if the FDA becomes aware of a substantial scientific
issue essential to product efficacy or safety. For more information on Special
Protocol Assessment, please visit:
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm080571.pdf.

About Hyperphosphatemia

In the United States, according to data from the U.S. Renal Data System, there
are approximately 600,000 patients with end-stage renal disease, or ESRD, and
the number of ESRD patients is projected to rise in the future. The majority
of ESRD patients in the United States, over 400,000, require dialysis.
Worldwide, there are approximately 2.8 million patients with ESRD, with the
majority of ESRD patients, over 2 million, requiring dialysis. Phosphate
retention and the resulting hyperphosphatemia in patients with ESRD on
dialysis are usually associated with secondary hyperparathyroidism, renal
osteodystrophy, soft tissue mineralization and the progression of renal
failure. ESRD patients usually require treatment with phosphate-binding agents
to lower and maintain serum phosphorus at acceptable levels. The need for
alternative phosphate-binding agents has long been recognized, especially
given the increasing prevalence of ESRD as well as shortcomings with current
therapies. Zerenex has the potential to be an effective and safe treatment in
lowering and/or maintaining normal serum phosphorus levels in patients with
ESRD and hyperphosphatemia.

The market for phosphate binders to treat hyperphosphatemia in ESRD patients
is approaching $1.5 billion worldwide.

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), an
oral, ferric iron-based compound that has the capacity to bind to phosphate
and form non-absorbable complexes. Zerenex has completed a U.S.-based Phase 3
clinical program for the treatment of hyperphosphatemia (elevated phosphate
levels) in patients with end-stage renal disease, conducted pursuant to a
Special Protocol Assessment (SPA) agreement with the FDA, and Keryx expects to
submit an NDA with the FDA and a MAA with the EMA in the second quarter of
2013. Zerenex is also in Phase 2 development in the U.S. for the management
of phosphorus and iron deficiency in anemic patients with Stage 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, and the clinical benefits to be
derived from Zerenex (ferric citrate), as well as 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: risks related to the timing
for submission of the NDA and MAA and whether the FDA and EMA, respectively,
will accept such submissions for review following submission and ultimately
approve them; whether the FDA and EMA will concur with the our interpretation
of our Phase 3 study results or the conduct of the study; our ability to
successfully and cost-effectively complete clinical trials, submit new drug
applications and obtain marketing approvals for Zerenex; 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 risk that the
data (both safety and efficacy) from the ongoing Phase 2 study in non-dialysis
dependent chronic kidney disease will be negative or inconclusive; our ability
to meet anticipated development timelines for Zerenex due to clinical trial
results, manufacturing capabilities or other factors; our Japanese partner's
ability to successfully obtain marketing approval for ferric citrate in Japan;
uncertainties related to the regulatory process; whether, if Zerenex receives
approval, it will be successfully distributed and marketed; whether the
patents and patent applications owned or licensed by the Company will protect
the Company's technology and prevent others from infringing it; 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, and the FDA.gov website, is not incorporated by reference into
this press release and is included for reference purposes only.

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

SOURCE Keryx Biopharmaceuticals, Inc.

Website: http://www.keryx.com
 
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