Keryx Biopharmaceuticals, Inc. (NASDAQ:KERX), a company focused on
bringing innovative medicines to people with kidney disease, today
announced two presentations of data on Auryxia® (ferric citrate) at
the 2017 American Society of Nephrology (ASN) Annual Meeting being
held October 31 - November 5, 2017 in New Orleans. The
presentations are based on post-hoc analysis of the Phase 3 study
of ferric citrate in adults with iron deficiency anemia and
non-dialysis dependent chronic kidney disease (NDD-CKD). In an oral
presentation, Geoffrey Block, M.D., described the effect of ferric
citrate on fibroblast growth factor (FGF23), a phosphate-regulating
hormone that is associated with chronic kidney disease
progression1. Separately, a poster presentation showed the effect
of ferric citrate on serum phosphorus in patients with normal and
elevated baseline phosphorus levels.
In the U.S., Auryxia is FDA-approved as a
phosphate binder indicated for the control of serum phosphorus
levels in adult patients with chronic kidney disease on dialysis.
Keryx is seeking to expand the indication for Auryxia to include
the treatment of iron deficiency anemia in people with non-dialysis
dependent chronic kidney disease. A supplemental new drug
application is under review by the U.S. FDA, with a Prescription
Drug User Fee Act (PDUFA) target action date of November 6,
2017.
“A highlight for us at this year’s Kidney Week
is Dr. Block’s oral presentation, which suggests that ferric
citrate may reduce FGF23 through several, potentially independent
pathways in patients with CKD and iron deficiency anemia,” said
John Neylan, M.D., chief medical officer of Keryx
Biopharmaceuticals. “The presentation of these data support our
commitment to advancing the science of chronic kidney disease to
improve the care of people living with this serious disease.”
“FGF23 is emerging as an important biomarker of
chronic kidney disease,” said Geoffrey Block, M.D., director of
clinical research at Denver Nephrology. “A potential oral treatment
option for iron deficiency anemia in patients with non-dialysis
dependent CKD, which also reduces FGF23, could be important in the
management of CKD.”
The two post-hoc analyses were derived from a
16-week, randomized, placebo-controlled Phase 3 study that
evaluated ferric citrate for the treatment of iron deficiency
anemia in adults with non-dialysis dependent chronic kidney
disease. As previously published in January 2017 in the Journal of
the American Society of Nephrology (JASN), the results from the
Phase 3 study demonstrated that patients treated with Auryxia
(n=117) for 16-weeks achieved a statistically significant increase
in hemoglobin and two other iron measurements, transferrin
saturation (TSAT) and ferritin, compared to placebo (n=116). The
mean reduction in serum phosphorus over 16 weeks in ferric
citrate-treated patients was modest, but statistically significant
compared with patients in the placebo group. In addition, the
incidence of hypophosphatemia reported as an adverse event in
ferric citrate-treated patients was low at <1 percent compared
to 1.7 percent in the placebo group.
Oral presentation examining effect of
ferric citrate on FGF23“Ferric Citrate Reduced FGF23 in
Patients with Non-Dialysis Dependent Chronic Kidney Disease
(NDD-CKD) and Iron Deficiency Anemia (IDA) Irrespective of the
Change in Serum Phosphate (P)” Oral presentation #TH-OR038.
FGF23 is a phosphate regulating hormone that is
associated with chronic kidney disease progression1. It increases
as chronic kidney disease progresses and increases with the
presence of iron deficiency anemia2. Elevated levels of this
hormone are associated with increased risk of cardiovascular
disease and death in chronic kidney disease patients3. There are
many overlapping and complicating factors that can impact FGF23,
including changes in phosphorus levels and iron levels in the
body4.
In the oral presentation, after 16 weeks of
treatment with Auryxia in adults with non-dialysis dependent
chronic kidney disease and iron deficiency anemia, FGF23 levels
were significantly reduced (Table 1). Post-hoc analysis of a Phase
3 study further examined if the reductions in FGF23 levels tracked
with baseline serum phosphorus and baseline iron levels. Data
presented at the meeting today showed reductions in FGF23 levels
occurred irrespective of a patient’s baseline phosphorus level or
baseline iron measure level (Table 2). These data suggest Auryxia
may reduce FGF23 via several, potentially independent pathways in
patients with chronic kidney disease and iron deficiency anemia via
reductions in serum phosphorus levels and/or increases in iron
stores.
Table 1: Effect of Ferric Citrate on
FGF23, Phase 3 Study
|
Ferric Citrate |
Placebo |
p-value |
Variables |
Baseline(n=116, cFGF23, n=117
iFGF23) |
Week 16(n=85 cFGF23, n=86
iFGF23) |
Baseline(n=113, cFGF23, n=114
iFGF23) |
Week 16(n=79, cFGF23, n=80
iFGF23) |
Median iFGF23, pg/mL |
134.0 |
105.0 |
134.3 |
119.5 |
<0.001 |
Median cFGF23, RU/mL |
364.0 |
232.5 |
305.8 |
309.4 |
<0.001 |
FGF23=fibroblast growth factor 23; cFGF = c-terminal FGF,
iFGF=intact FGF |
*n
dependent upon number of laboratory values available |
**
Between-group changes were evaluated from baseline to the end of
week 16 using Wilcoxon rank sum test for nonparametric data. |
|
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Table 2: Effect of Ferric Citrate on
FGF23 by baseline phosphorous level, baseline iron level, Phase 3
Study
|
|
BL P < 3.5 mg/dL |
BL P 3.5 <4.5 mg/dL |
BL P 4.5 <5.5 mg/dL |
BL P > 5.5 mg/dL |
BL TSAT <20% |
BL TSAT > 20% |
i-FGF23(pg/mL) n=117 |
BL median |
89.7 |
118.1 |
205.3 |
250.2 |
117.1 |
143.5 |
16 wks median |
85.0 |
102.2 |
152.0 |
156.6 |
101.4 |
113.0 |
|
P-value* |
0.340 |
0.004 |
0.012 |
0.031 |
<0.001 |
0.019 |
c-FGF23(RU/mL)n=116 |
BL median |
266.0 |
330.5 |
415.8 |
576.8 |
427.4 |
297.8 |
16 wks median |
173.1 |
198.3 |
328.0 |
592.1 |
259.3 |
207.1 |
|
p-value* |
0.021 |
<0.001 |
0.027 |
0.297 |
<0.001 |
0.009 |
*P-values
are from a non-parametric (Wilcoxon signed-rank) test |
BL P =
baseline phosphorus level |
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|
|
Poster presentation examining effect of ferric citrate
on normal phosphorus levels“Ferric Citrate Lowered Serum
Phosphate Only When Elevated in Patients with Non-Dialysis
Dependent (NDD) CKD and Iron Deficiency Anemia (IDA)” Poster #
TH-PO514.
In a poster presentation today, a post-hoc
analysis of this Phase 3 study was conducted to further examine the
effect of ferric citrate on serum phosphorus when patients were
stratified by baseline phosphorus, kidney function or FGF23 levels.
The analysis showed that in patients treated with ferric citrate to
increase hemoglobin levels, the mean reduction in serum phosphorus
differed by baseline phosphorus levels. Specifically, serum
phosphorus levels decreased only in patients with elevated serum
phosphorus at baseline, especially those with the highest baseline
serum phosphorus levels. Importantly, in patients with normal
phosphate levels, there was no discernible change in phosphorus
when treated with ferric citrate (Table 3). These data provide
further evidence that when ferric citrate was used as a treatment
for iron deficiency anemia in patients with normal phosphorus
levels at baseline, mean phosphorus remained in the normal range
(3.5 mg/dL and 5.5 mg/dL) and the risk of hypophosphatemia was
low.
Table 3: Change in serum phosphorus by
baseline phosphorous levels
|
|
BL P <3.5 mg/dL |
BL P 3.5 - <4.5 mg/dL |
BL P 4.5 - <5.5 mg/dL |
BL P >5.5 mg/dL |
Serum P (n=115) |
Change from baseline to week 16 |
+0.24 |
-0.26 |
-0.97 |
-1.74 |
|
p-value** |
0.115 |
0.002 |
<0.001 |
0.032 |
** p-values
are from a parameter t-test |
BL P =
baseline phosphorus level |
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About Auryxia® (ferric
citrate) tabletsAuryxia (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 adults 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. For more information about
Auryxia and the U.S. full prescribing information, visit
www.Auryxia.com.
Use of ferric citrate in patients with IDA,
NDD-CKD, as highlighted above, is investigational and has not been
determined to be safe or efficacious.
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.
Forward Looking Statements Some
of the statements included in this press release, particularly
those regarding the commercialization and ongoing clinical
development of Auryxia and the submission of an sNDA to the FDA to
expand the label of ferric citrate to include the treatment of IDA
in adults with stage 3-5 NDD-CKD and the potential approval in this
indication and the impact thereof on Keryx, 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; whether we can maintain our operating expenses to
projected levels while continuing our current clinical, regulatory
and commercial activities; the risk that the FDA may not concur
with our interpretation of our Phase 3 study results in 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; our
ability to continue to supply Auryxia to the market; 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, Inc., with headquarters in
Boston, Massachusetts, is focused on the development and
commercialization of innovative medicines that provide unique and
meaningful advantages to people with kidney disease. The Keryx team
consists of approximately 200 committed people working with passion
to advance the care of people with this complex disease. In
September 2014, the U.S. Food and Drug Administration approved
Keryx’s first medicine, Auryxia® (ferric citrate) tablets. For more
information about Keryx, please visit www.keryx.com.
References
1Wolf M. Update on fibroblast growth factor 23
in chronic kidney disease. Kidney Int. 2012;82(7):737–747.
2David V, et al. Inflammation and functional
iron deficiency regulate fibroblast growth factor 23 production.
Kidney Int. 2016;89(1):136–146.
3Isakova T, Xie H, Yang W, et al. Chronic Renal
Insufficiency Cohort (CRIC) Study Group. Fibroblast growth factor
23 and risks of mortality and end-stage renal disease in patients
with chronic kidney disease. JAMA. 2011;305(23):2432–2439.Scialla
JJ, Xie H, Rahman M, et al. Chronic Renal Insufficiency Cohort
(CRIC) Study Investigators. Fibroblast growth factor-23 and
cardiovascular events in CKD. J Am Soc Nephrol.
2014;25(2):349–360.
4David V, et al. Inflammation and functional
iron deficiency regulate fibroblast growth factor 23 production.
Kidney Int. 2016;89(1):136–146. Wolf M. Update on fibroblast growth
factor 23 in chronic kidney disease. Kidney Int.
2012;82(7):737–747.
KERYX BIOPHARMACEUTICALS
CONTACTS:Amy SullivanSenior Vice President, Corporate
AffairsT: 617.466.3519amy.sullivan@keryx.com
Lora PikeSenior Director, Investor Relations
& Corporate CommunicationsT:
617.466.3511lora.pike@keryx.com
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