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 StudyThe 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 AnemiaIt 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.
About Auryxia™ (ferric citrate)Auryxia™ (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 patients with chronic kidney disease
(CKD) on dialysis. The U.S. approval of Auryxia was based on data
from the company's Phase 3 registration program. 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.
Auryxia binds with dietary phosphate in the GI tract and
precipitates as ferric phosphate. The unbound portion of Auryxia
has been shown to increase serum iron parameters including ferritin
and transferrin saturation (TSAT), whereas these parameters
remained relatively constant in patients treated with active
control (Renvela® and/or Phoslo®). Iron absorption from Auryxia may
lead to excessive elevations in iron stores. Accordingly,
physicians should assess and monitor iron parameters before
starting and while on Auryxia, and may need to decrease or
discontinue IV iron for these patients. The most common adverse
events for Auryxia treated patients were gastrointestinal-related,
including diarrhea, nausea, vomiting and constipation. For more
information about Auryxia and the U.S. full prescribing
information, visit www.Auryxia.com.
IMPORTANT U.S. SAFETY INFORMATION FOR AURYXIA™ (ferric
citrate) Contraindication: Patients
with iron overload syndrome, e.g. hemochromatosis, should not take
Auryxia™ (ferric citrate).
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.
For Full Prescribing Information for Auryxia, please
visit http://auryxia.com/important-safety-information/
About Keryx Biopharmaceuticals, Inc. Keryx
Biopharmaceuticals, with headquarters in Boston, is focused on
bringing innovative medicines to market for people with renal
disease. In December 2014, the company launched its first
FDA-approved medicine, Auryxia™ (ferric citrate) for the control of
elevated serum phosphorus levels, or hyperphosphatemia, in patients
with chronic kidney disease (CKD) on dialysis, in the United
States. In January 2014, ferric citrate was approved for the
treatment of patients with all stages of CKD in Japan, where it is
being marketed as Riona® by Keryx's Japanese partner, Japan Tobacco
Inc. and Torii Pharmaceutical Co. Ltd. In September 2015, the
European Commission granted European market authorization for
Fexeric® (ferric citrate coordination complex) for the control of
hyperphosphatemia in adults with non-dialysis and
dialysis-dependent chronic kidney disease. For more information
about Keryx, please visit www.keryx.com
Forward-Looking Statements Some of the
statements included in this press release 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: the risk
that we may not be able to successfully market Auryxia in the
U.S. for patients with chronic kidney disease on dialysis; the risk
that the FDA may not concur with our interpretation of our Phase 3
study results, supportive data, conduct of the studies, or any
other part of our regulatory submission and could ultimately deny
approval of the ferric citrate for the treatment of iron deficiency
anemia (IDA) in adults with stage 3-5 non-dialysis dependent (NDD)
chronic kidney disease (CKD); 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.
KERYX BIOPHARMACEUTICALS CONTACTS:
Amy Sullivan
Vice President, Corporate Development and Public Affairs
T: 617.466.3519
amy.sullivan@keryx.com
Lora Pike
Senior Director, Investor Relations
T: 617-466-3511
lora.pike@keryx.com
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