FREMONT, Calif., June 22, 2016 /PRNewswire/ -- Ardelyx, Inc.
(NASDAQ: ARDX), a clinical-stage biopharmaceutical company focused
on gastrointestinal and cardio-renal diseases, today announced
updates to two of the Company's ongoing development programs.
Ardelyx today announced that, based on the positive outcome of a
recent End-of-Phase 2 (EoP2) meeting held with the U.S. Food and
Drug Administration (FDA), its ongoing Phase 2b clinical trial
evaluating tenapanor for the treatment of hyperphosphatemia for
end-stage renal disease (ESRD) patients on dialysis, may serve as
the first of two registration trials to support the filing of a new
drug application (NDA). Additionally, the Company today announced
the results of a pharmacodynamic (PD) study evaluating once daily
(QD) dosing of its product candidate, RDX227675, for the treatment
of hyperkalemia. With these positive results, Ardelyx is
accelerating its plans to commence a time to onset clinical trial
in patients with hyperkalemia.
The Company will be hosting a conference call and webcast today
at 8:30am ET to provide a detailed
update regarding these recent developments. Please call
1-877-253-8183 (US) or 973-200-3070 (International) to listen to
the conference call. The conference ID number for the live call
will be 34249750. Alternatively, a live webcast can be accessed by
visiting the investor section of Ardelyx's website at
ir.ardelyx.com. Following the webcast, an archived version of the
call will be available until July 6,
2016.
Overview of Updates to Ardelyx's Development Programs
Tenapanor for the Treatment of Hyperphosphatemia for ESRD
Patients on Dialysis
Ardelyx recently met with the FDA for an EoP2 meeting regarding
tenapanor for the treatment of hyperphosphatemia for ESRD patients
on dialysis. The FDA guided Ardelyx to use the results of the
placebo-controlled randomized withdrawal portion of the trial as
the primary endpoint for its ongoing clinical trial, rather than as
a secondary endpoint, in order for the trial to serve as one of two
well-controlled studies to support the registration of tenapanor
for the treatment of hyperphosphatemia for ESRD patients on
dialysis. The overall study design will not be changed, but the
Company is increasing the number of patients to be enrolled in the
trial from 150 to 200 to further strengthen the trial and maintain
a power of 90%.
The trial is designed to include an 8-week treatment period
followed by a 4-week randomized withdrawal (RW) period where
patients either stay on their current dose of tenapanor or are
randomized to receive placebo. The primary endpoint will now
assess the difference in the change, between a pool of subjects
that respond to tenapanor during the initial 8 weeks of the trial
and those on placebo from the end of the 8-week treatment period to
the end of the 4-week RW period. Responders are defined as patients
that demonstrate a ≥ 1.2 mg/dL decrease in serum phosphorus from
baseline during the 8-week treatment period. The
primary endpoint is powered at 90% to show a ≥ 1.5 mg/dL placebo
adjusted effect. The FDA has accepted the new statistical analysis
plan submitted to reflect these changes. As a result of the
increase in enrollment, Ardelyx now expects results from the
ongoing trial to be reported in the first quarter of 2017, as
compared to prior guidance of the second half of 2016.
"Tenapanor, if successfully commercialized, will provide a
profound improvement in the way dialysis patients are treated. It
would be the first agent approved for patients with
hyperphosphatemia that is not a phosphate binder, and, as a
consequence, results in a dramatically lower pill burden and
overall mass required, as well as eliminating the need to be taken
with all three meals and snacks," commented Mike Raab, President and Chief Executive Officer
of Ardelyx. "We are extremely pleased with the outcome of our
EoP2 meeting with the FDA and fully support the Agency's suggested
changes to our ongoing Phase 2b clinical trial's primary endpoint
and statistical analysis plan."
RDX227675 for the Treatment of Hyperkalemia
Separately, Ardelyx also announced today that it has received
positive results from its QD dosing arm of the RDX227675 PD study
in healthy adult volunteers. Ardelyx previously announced positive
results in January 2016 from its PD
trial evaluating twice daily (BID) and three times daily (TID)
doses of RDX227675 in 60 healthy adult volunteers. The BID and TID
doses successfully demonstrated the ability of RDX227675 to bind
potassium in the gastrointestinal tract and RDX227675 was generally
well-tolerated at all doses administered up to 27.5 g/day. Results
from the new cohort, which evaluated the QD administration of
RDX227675, demonstrated that a 13.8 g dose exhibited similar stool
and urine potassium results to the previously-reported BID and TID
dosing with the same total daily dose of 13.8 g (maximum mean
increases in stool potassium of about 1,500 mg/day, with decreases
in urinary potassium of about 900 mg/day). RDX227675
delivered once daily also was well-tolerated in these
individuals. Based on these data, the Company has determined
that once or twice daily dosing will be the most appropriate dosing
regimens for further development and evaluation in the treatment of
hyperkalemia in its upcoming trials.
"Treatment of hyperkalemia is an important and emerging market,"
said Paul Korner, MD, Executive Vice
President and Chief Medical Officer. "As a result of hyperkalemia,
many physicians opt to lower the dose of, or discontinue,
potentially life-saving drugs such as ACE inhibitors that, as a
side-effect, tend to increase serum potassium, rather than risk the
potential dangers of this side effect in their CKD or heart failure
patients. In addition, the RDX227675 formulation does not
contain sodium or sorbitol, has significantly improved
palatability, and with a convenient once or twice daily dosing, has
the potential to provide significant benefits to patients with
hyperkalemia."
Following these encouraging results, Ardelyx will now accelerate
the commencement of a previously planned Phase 2b trial designed to
evaluate the rate of onset of action of RDX227675 along with safety
and efficacy in patients with chronic kidney disease (CKD) with or
without heart failure (HF), one of the target patient populations
for RDX227675. This study is in accordance with FDA's request
to evaluate onset of action of RDX227675 and is in-line with the
Company's strategy to develop a robust package insert for
prescribers that includes competitive clinical data similar to
those of existing potassium binders. Ardelyx expects to commence
this Phase 2b clinical trial in the fourth quarter of 2016, with a
target enrollment of approximately 60 patients. Results from this
trial are expected to be available in the first half of 2017. The
Phase 2b clinical trial will not affect the expected timing or
design of the previously announced Phase 3 clinical trial for
RDX227675, which is still on track to initiate in the fourth
quarter of 2016.
"We have been unwavering in our focus to provide hyperkalemia
patients with an efficacious product that is highly palatable and
convenient as we understand that daily administration of multiple
grams of any agent is not trivial," added Dr. Korner.
About Tenapanor
Tenapanor is a minimally-systemic small molecule that acts
locally in the gastrointestinal (GI) tract to inhibit the sodium
transporter NHE3 and reduce sodium and phosphorus uptake from the
gut. In human studies of orally-administered tenapanor, the drug
was detected in the blood in only 0.7% of more than 3,000 collected
serum samples, and even in those, at very low levels (< 1.5
ng/mL). The Company has evaluated tenapanor in 18 human clinical
trials in over 1,500 individuals, to date. The Company is currently
evaluating tenapanor in two different programs:
- Irritable Bowel Syndrome with Constipation (IBS-C): In the
fourth quarter of 2015, the Company initiated two pivotal Phase 3
clinical trials (T3MPO-1 and T3MPO-2) evaluating tenapanor in
patients with IBS-C, and currently expects results from those
trials in 2017. In a Phase 2b clinical trial evaluating a 50 mg
dose of tenapanor BID, the study met its primary endpoint of an
increase in the complete spontaneous bowel movement (CSBM)
responder rate, demonstrating its ability to improve symptoms of
IBS-C. Most secondary endpoints, including abdominal pain, the
overall responder rate, and other abdominal and IBS-C symptoms,
demonstrated statistically significant and clinically meaningful
improvements when compared to placebo, as well. Based on reports in
the literature regarding the prevalence of IBS in the U.S.
population and the percentage of individuals who have IBS-C as
compared to other forms of IBS, the Company believes that about
1.4% of the U.S. population, or approximately 4.4 million
individuals, suffer from IBS-C, with approximately 1.0 million of
those patients being diagnosed. Additionally, the Company estimates
that there are about 6.6 million IBS-C patients in Europe and about 3.4 million in Japan.
- Hyperphosphatemia in ESRD patients on dialysis: In the fourth
quarter 2015, the Company initiated a Phase 2b clinical trial to
evaluate the optimal dosing regimen of tenapanor for the treatment
of hyperphosphatemia in ESRD patients on dialysis. Pending positive
data, the clinical trial may be considered the first of two
registration trials to support the filing of a new drug application
(NDA) for tenapanor in this indication. The Company currently
expects to announce results from this ongoing trial in the first
quarter of 2017. Results from an earlier Phase 2b clinical trial in
this indication were announced in 2015. In that study, there was a
statistically significant dose-related decrease in serum phosphorus
levels for tenapanor-treated patients compared to patients
receiving placebo (p=0.012). It was noted, however, that the rate
of diarrhea and the rate of discontinuations due to diarrhea, were
higher than expected for patients that were treated with tenapanor,
based on previous clinical trials. Higher discontinuations rates
due to diarrhea were observed primarily in the 30 mg QD and 30 mg
BID dose groups. The ongoing registration clinical trial has a
down-titration arm to optimize tolerance while retaining
efficacy. The overall safety profile of the previously
completed Phase 2b trial remained consistent with that observed in
previous tenapanor trials. The Company estimates, based on
phosphate binder utilization, that there are approximately 290,000,
225,000, and 220,000 ESRD patients with hyperphosphatemia in
the United States, Europe, and Japan, respectively.
About RDX227675
RDX227675 is Ardelyx's proprietary oral, non-absorbed,
potassium-binding polymer based on sodium polystyrene sulfonate
(SPS), a well-known and well-characterized polymer, also known as
Kayexalate®. Ardelyx has made numerous improvements to the polymer
by engineering into RDX227675 several key physical and chemical
modifications in an effort to improve various properties. In a
separate single center, randomized, crossover study to evaluate
various oral formulations of RDX227675 in healthy adult volunteers,
RDX227675 consistently outperformed SPS in all aspects of the taste
assessments, including mouth feel, texture, and flavor. A human
adult pharmacodynamic study has shown that 13.8 g of RDX227675,
whether delivered once, twice or three times daily, results in a
similar increase of stool potassium of about 1,500 mg/day, with
decrease in urinary potassium of about 900 mg/day. The
Company expects to begin a Phase 2b trial designed to evaluate the
rate of onset of action and a Phase 3 clinical program with
RDX227675 in fourth quarter 2016. The Company believes that
hyperkalemia (HK) affects about 900,000 individuals with Stage 3b
or Stage 4 CKD in the United
States as well as approximately 900,000 patients with HF and
up to 200,000 ESRD patients on dialysis in the United States. Ardelyx has filed a patent
application covering the composition of matter of RDX227675.
About Ardelyx, Inc.
Ardelyx is a clinical-stage biopharmaceutical company focused on
the discovery, development, and commercialization of innovative,
minimally-systemic, small molecule therapeutics that work
exclusively in the gastrointestinal tract to treat gastrointestinal
and cardio-renal diseases. Ardelyx has developed a proprietary drug
discovery and design platform enabling it, in a rapid and
cost-efficient manner, to discover and design novel drug
candidates. Utilizing this platform, Ardelyx has discovered and
designed tenapanor, which it is evaluating for the treatment of
IBS-C and management of hyperphosphatemia in patients with ESRD on
dialysis. In addition to tenapanor, Ardelyx is developing
RDX227675, a non-absorbed polymer for the treatment of
hyperkalemia, or high potassium, a problem prevalent in patients
with kidney and heart disease. Ardelyx is also advancing several
research programs focused in gastrointestinal and cardio-renal
diseases. Ardelyx is located in Fremont,
California. For more information, please visit Ardelyx's
website at www.ardelyx.com.
Forward Looking Statements
To the extent that statements contained in this press release
are not descriptions of historical facts regarding Ardelyx, they
are forward-looking statements reflecting the current beliefs and
expectations of management made pursuant to the safe harbor of the
Private Securities Reform Act of 1995, including the potential for
tenapanor in treating IBS-C patients, the expected timing for the
receipt of the results from Ardelyx's two ongoing Phase 3 clinical
trials evaluating tenapanor for the treatment of IBS-C, the
potential for tenapanor in treating hyperphosphatemia in ESRD
patients on dialysis, the expected timing of the results of the
ongoing clinical trial evaluating tenapanor for the treatment of
hyperphosphatemia in ESRD patients on dialysis, the potential for
the ongoing clinical trial evaluating tenapanor for the treatment
of hyperphosphatemia in ESRD patients on dialysis to serve as the
first of two well-controlled clinical trials to support
registration, the potential for RDX227675 in treating hyperkalemia
in CKD patients, the expected timing of the initiation of the Phase
2b and Phase 3 clinical trials evaluating RDX227675 in treating
hyperkalemia in CKD patients and the expected timing of the results
of the Phase 2b trial, and the potential of Ardelyx's drug
discovery and design platform. Such forward-looking statements
involve substantial risks and uncertainties that could cause the
development of tenapanor, RDX227675, or Ardelyx's future results,
performance or achievements to differ significantly from those
expressed or implied by the forward-looking statements. Such risks
and uncertainties include, among others, the uncertainties inherent
in research and the clinical development process and the
uncertainties in the manufacture of clinical trial material,
including process development, scale up and tech transfer of
manufacturing processes. Ardelyx undertakes no obligation to update
or revise any forward-looking statements. For a further description
of the risks and uncertainties that could cause actual results to
differ from those expressed in these forward-looking statements, as
well as risks relating to Ardelyx's business in general, please
refer to Ardelyx's Quarterly Report on Form 10-Q filed with the
Securities and Exchange Commission on May 9,
2016, and its future current and periodic reports to be
filed with the Securities and Exchange Commission.
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SOURCE Ardelyx