Keryx Biopharmaceuticals, Inc.
05.11.2013 13:30
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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, 2013-11-05 13:30 CET (GLOBE NEWSWIRE) --Keryx Biopharmaceuticals,
Inc. (Nasdaq:KERX) today announced successful top-line results from its Phase 2
study of Zerenex(tm) (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)
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Baseline 4.7 4.5
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End of Treatment1 (Week 12) 4.4 3.9
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Treatment Difference p-value2 p < 0.001
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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)
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Baseline 21 22
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End of Treatment1 (Week 12) 20 32
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Treatment Difference p-value2 p < 0.001
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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)
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Baseline 110 116
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End of Treatment1 (Week 12) 106 189
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Treatment Difference p-value2 p < 0.001
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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)
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Baseline 10.6 10.5
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End of Treatment1 (Week 12) 10.4 11
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Treatment Difference p-value2 p < 0.001
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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)
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Baseline 263 319
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End of Treatment1 (Week 12) 293 200
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Treatment Difference p-value2 P=0.017
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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)
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Baseline 511 468
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End of Treatment1 (Week 12) 579 316
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Treatment Difference p-value2 p < 0.001
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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)
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Hemoglobin < 9.0 g/dL 9 1
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Serum Phosphorus >= 6.0 mg/dL 2 0
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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
News Source: NASDAQ OMX
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DGAP-News: 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
| Source: EQS Group AG