FREMONT, Calif., Dec. 3, 2019 /PRNewswire/ -- Ardelyx, Inc.
(Nasdaq: ARDX), a specialized biopharmaceutical company focused on
developing first-in-class medicines to improve treatment for people
with cardiorenal diseases, today reported positive topline results
from PHREEDOM, a long-term Phase 3 study evaluating the efficacy
and safety of tenapanor as monotherapy for the treatment of
hyperphosphatemia in patients with chronic kidney disease (CKD) on
dialysis. In the study, patients randomized to the tenapanor arm
were treated in a 26-week open-label treatment period and were then
re-randomized to a 12-week double-blind, placebo-controlled
randomized withdrawal period. The PHREEDOM study met its primary
endpoint demonstrating a statistically significant difference in
least square (LS) mean serum phosphorus change (-1.4 mg/dL,
p<0.0001), as compared to placebo. During the 26-week treatment
period, 77% of tenapanor-treated patients in the intent-to-treat
population (n=408) had a decrease in serum phosphorus, with a mean
reduction from baseline of 2.0 mg/dL. Tenapanor is an
investigational, first-in-class, phosphate absorption inhibitor
being developed to treat hyperphosphatemia in patients with CKD on
dialysis. If approved, tenapanor will be the only non-binder
treatment for the control of serum phosphorus in patients with CKD
on dialysis.
"If approved, tenapanor is poised to change the way we manage
hyperphosphatemia in patients on dialysis," said Myles Wolf, M.D., MMSc, Charles Johnson, M.D. professor of medicine and
chief of Duke Nephrology. "Tenapanor would be a first-in-class
therapy that targets the primary pathway of phosphate absorption
to significantly lower serum phosphate while
requiring patients to take just one small pill twice per
day. This would make tenapanor an important innovation and
potentially an ideal first-line therapy for patients receiving
dialysis for whom new effective treatments are desperately
needed."
"These results are very exciting and represent a capstone to our
tenapanor clinical development program, which is focused on the
development of a new and important therapy for patients with
hyperphosphatemia," said Mike Raab,
president and chief executive officer of Ardelyx. "Based on the
PHREEDOM data that demonstrate tenapanor as an effective
monotherapy, and the previously released AMPLIFY data that
demonstrate the benefits of a dual mechanism approach with
tenapanor plus binders in those who require more aggressive
phosphate management, it is clear that tenapanor has a role to play
in the management of all dialysis patients with hyperphosphatemia.
With these results in hand, our focus will now turn to completing
and submitting our NDA, which we expect in mid-2020."
PHREEDOM
Key Topline Results
Primary Endpoint:
As compared to patients treated with placebo, patients in the
efficacy analysis set treated with tenapanor had a statistically
significant difference in LS mean serum phosphorus change from the
end of the 26-week treatment period to the endpoint visit in the
12-week randomized withdrawal period (-1.4 mg/dL,
p<0.0001).
Safety:
Tenapanor was generally well-tolerated. As anticipated due to
the mechanism of action, the most common self-reported adverse
event was loose stools/diarrhea at an incidence rate of 52.5%, with
approximately 90% of these events judged by the investigator to be
mild to moderate in nature. The majority of the events were
reported within the first five days of treatment and were transient
notwithstanding continued treatment with tenapanor. In the 26-week
open-label treatment period, 16% of the tenapanor-treated patients
discontinued treatment due to diarrhea. Additionally, during the
randomized withdrawal period, only 0.8% of tenapanor-treated
patients discontinued due to diarrhea.
In the safety analysis set of the 26-week open-label treatment
period, which included tenapanor (n=419) and sevelamer (n=137),
17.2% of tenapanor-treated patients compared to 22.6% of
sevelamer-treated patients experienced a serious adverse event. The
median dose for tenapanor was 60 milligrams per day throughout the
study and the median dose for sevelamer was 4.8 grams per day after
randomization and increased to 7.2 grams per day by the end of the
26-week open-label treatment period.
NORMALIZE
Initial Results
Patients completing the PHREEDOM trial from both the tenapanor
arm and the sevelamer active safety control arm had the option to
participate in NORMALIZE, an ongoing open-label 18-month extension
study. The goal of this study is to obtain real-world evidence
regarding the dual mechanism of tenapanor and sevelamer to reduce
patients' serum phosphorus levels to normal (<4.6 mg/dL) while
minimizing medication burden.
Patients entering the study from the tenapanor arm with serum
phosphorus levels in the normal range are followed with no
medication changes. Patients entering the study from the tenapanor
arm with serum phosphorus ³4.6 mg/dL have sevelamer tablets added
incrementally to achieve normal serum phosphorus levels. Patients
entering the study from the sevelamer active safety control arm
have tenapanor tablets added to their treatment regimen and have
sevelamer tablets withdrawn based on their serum phosphorus value,
to achieve normal serum phosphorus levels.
In this initial analysis, 96% of eligible patients have chosen
to enroll into NORMALIZE. Of the 73 patients thus far treated
for more than one month of treatment, 42% have achieved
normal serum phosphorus of less than 4.6 mg/dL and of
those, 58% have accomplished this with either tenapanor alone or
with tenapanor in combination with only one to three sevelamer
tablets per day. These data represent a 45% improvement compared to
current treatment practice data reported in the June 2019 Dialysis Outcomes Practice Patterns
Study (DOPPS) Practice Monitor.
PHREEDOM Study Design
PHREEDOM is a one-year study with a 26-week open-label treatment
period and a 12-week double-blind, placebo-controlled randomized
withdrawal period followed by a 14-week open-label safety extension
period. The study randomized a total of 564 patients with CKD on
dialysis who had a serum phosphorus level between 6.0 mg/dL and
10.0 mg/dL and had an increase in serum phosphorous of at least 1.5
mg/dL after an up to 3-week phosphate binder wash-out period.
Patients were randomized 3:1 to either the tenapanor arm (n=423,
n=408 intent to treat) or the active safety control arm (sevelamer
n=141). Those patients randomized to the active safety control arm
are treated with sevelamer for 52 weeks. Patients in the tenapanor
arm received tenapanor twice daily at a starting dose of 30 mg with
dose adjustments allowed based on serum phosphorus level and
gastrointestinal tolerability. At the end of the 26-week treatment
period, patients in the tenapanor arm were randomized 1:1 to enter
the randomized withdrawal period and either remain on the tenapanor
dose they were taking or receive placebo for up to an additional 12
weeks. After the randomized withdrawal period, patients then
continued on the study for an additional three months as part of
the long-term safety extension. Patients in the active safety
control arm received sevelamer at an initial dose based on its
package insert with dose changes allowed at the discretion of the
principal investigator for up to one year.
The primary efficacy endpoint of the study was the difference in
change in serum phosphorus between the pooled tenapanor-treated
patients and placebo-treated patients in the efficacy analysis set
from the end of the 26-week treatment period to the endpoint visit
of the 12-week randomized withdrawal period. The efficacy analysis
set (n=131), which was accepted by the U.S. Food and Drug
Administration as the primary analysis set, included patients who
completed the 26-week treatment period and achieved a 1.2 mg/dL
decrease in serum phosphorus in the same period.
About Tenapanor for Hyperphosphatemia
Tenapanor, discovered and developed by Ardelyx, is a
first-in-class, proprietary, minimally absorbed, oral, medicine in
late-stage clinical development for the control of serum phosphorus
in patients with CKD on dialysis. Tenapanor has a unique mechanism
of action and acts locally in the gut to inhibit the sodium
hydrogen exchanger 3 (NHE3). This results in the tightening of the
epithelial cell junctions, thereby significantly reducing
paracellular uptake of phosphate, the primary pathway of phosphate
absorption. In addition to the positive results of the PHREEDOM
trial, the company previously reported results from its first Phase
3 monotherapy study with tenapanor in patients with CKD on
dialysis, reporting that the primary endpoint was met (p=0.01).
About Hyperphosphatemia
Hyperphosphatemia is a serious condition resulting in an
abnormally elevated level of phosphorus in the blood that is
estimated to affect more than 745,000 dialysis patients in major
developed countries. The kidney is the organ responsible for
regulating phosphorus levels, but when kidney function is
significantly impaired, phosphorus is not adequately eliminated
from the body. As a result, hyperphosphatemia is a nearly universal
condition among people with CKD and especially those on dialysis.
Despite treatment with phosphate binders (the only approved therapy
for hyperphosphatemia), approximately 70% of CKD patients on
dialysis continue to experience elevated phosphorus levels at any
point in time (Spherix Global Insights: RealWorld Dynamix, Dialysis
2018). Phosphorus levels greater than 5.5 mg/dL have been shown to
be an independent risk factor for cardiovascular morbidity and
mortality in patients requiring dialysis (Block 2004), and
internationally recognized treatment guidelines recommend lowering
elevated phosphate levels toward the normal range
(<4.6mg/dL).
Conference Call Information
The company will host a
conference call today, December 3,
2019 at 8:00 AM ET to discuss
the PHREEDOM findings. To participate in the conference call,
please call (855) 296-9612 (toll-free) or (920) 663-6277 (toll) and
reference call ID number 8065608. A webcast of the call and
accompanying slides can also be accessed by visiting the Investor
page of the company's website www.ardelyx.com and will be
available on the website for 60 days following the call.
About Ardelyx, Inc.
Ardelyx is focused on enhancing
the way people with cardiorenal diseases are treated by developing
first-in-class medicines. Ardelyx's cardiorenal pipeline includes
tenapanor, a treatment of hyperphosphatemia in people with chronic
kidney diseases (CKD) who are on dialysis, and RDX013, a potassium
secretagogue program for the potential treatment of high potassium,
or hyperkalemia, a problem among certain patients with kidney
and/or heart disease. In addition, Ardelyx has received approval of
IBSRELA® (tenapanor). To efficiently bring its
treatments to market, Ardelyx is pursuing strategic collaborations
for tenapanor for IBS-C and hyperphosphatemia in certain
territories. Ardelyx has established agreements with Kyowa Kirin
(formerly known as Kyowa Hakko Kirin) in Japan, Fosun Pharma in China and Knight Therapeutics in Canada. For more information, please visit
http://www.ardelyx.com and connect with us on Twitter @Ardelyx.
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
Ardelyx's product candidates in treating the diseases and
conditions for which they are being developed, the potential for
the use of tenapanor as monotherapy and as part of a dual mechanism
approach with tenapanor and binders for the treatment of
hyperphosphatemia, the potential for tenapanor with binders to
achieve serum phosphorus levels of less than 5.5 mg/dL and less
than 4.6 mg/dL, and Ardelyx's expected timing for an NDA submission
for tenapanor for hyperphosphatemia. Such forward-looking
statements involve substantial risks and uncertainties that could
cause the development of Ardelyx's product candidates 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 the clinical development process,
including the regulatory approval process. 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
November 6, 2019, and its future
current and periodic reports to be filed with the Securities and
Exchange Commission.
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SOURCE Ardelyx