FREMONT, Calif., Sept. 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 results from
AMPLIFY, a pivotal Phase 3 study of tenapanor in combination with
phosphate binders in patients with chronic kidney disease (CKD) on
dialysis whose hyperphosphatemia was not previously controlled with
binders alone. The AMPLIFY study met the primary endpoint and all
key secondary endpoints, including demonstrating a statistically
significant (p=0.0004) reduction in serum phosphorus levels for
patients treated with tenapanor and phosphate binders compared to
phosphate binders alone. Tenapanor is an investigational,
first-in-class, small molecule, non-binder, phosphate absorption
inhibitor being developed to treat hyperphosphatemia in patients
with CKD on dialysis.
"I believe tenapanor has the potential to change the landscape
of hyperphosphatemia treatment – finally, a novel agent that can
lower serum phosphorus alone or in conjunction with binders," said
Glenn Chertow, M.D., M.P.H.,
division chief of nephrology and professor of medicine at
Stanford University. "Faced with an
extremely high mortality rate of approximately 18% per year in
dialysis patients, we are very focused on managing and treating
elevated serum phosphorus. Elevated serum phosphorus is associated
with mortality, cardiovascular events and bone fracture among
patients receiving dialysis, and more than half of patients cannot
achieve control of hyperphosphatemia despite taking a fist full of
binders three times daily with meals. The AMPLIFY study results
provide convincing evidence that controlling hyperphosphatemia will
soon be within our reach."
Mike Raab, president and chief
executive officer of Ardelyx added, "We are thrilled with the
positive results from the AMPLIFY study demonstrating that
tenapanor can help significantly more patients achieve the
established serum phosphorus treatment goal of less than 5.5 mg/dL.
This result is striking as serum phosphorus levels above 5.5 mg/dL
are associated with increased mortality. For too long,
hyperphosphatemia management has been an enormous challenge for
patients and clinicians. With tenapanor, patients may finally be
able to achieve their treatment goal. We look forward to reporting
results from our second Phase 3 monotherapy study, PHREEDOM, in the
fourth quarter of this year. With additional positive results from
that trial, we will complete our New Drug Application for
tenapanor, encompassing two indications: monotherapy and
combination therapy for the treatment of hyperphosphatemia. The
promising results from AMPLIFY bring us one step closer to
providing this important medicine to patients with CKD on
dialysis."
Key Study Results
Efficacy
For the primary endpoint, patients treated in the tenapanor arm
(tenapanor in combination with phosphate binders, n=116) had a
statistically significant (p=0.0004) mean reduction in serum
phosphorus from baseline to the end of the four-week treatment
period of 0.84 mg/dL, as compared to those treated in the binder
arm (placebo in combination with phosphate binders, n=119) who had
a mean reduction of 0.19 mg/dL. Patients in the tenapanor arm had
statistically significant decreases in serum phosphorus during all
four weeks ranging from 0.84 to 1.21 mg/dL (p-values<0.0004).
During the treatment period, up to 49.1% of patients in the
tenapanor arm achieved a serum phosphorus of <5.5 mg/dL which
was statistically significant compared with up to 23.5% in the
binder arm (p-values≤0.0097). There was a statistically significant
22% to 24% reduction (p-values≤0.0027) in FGF23 levels in the
tenapanor arm as compared to the binder arm. Elevated levels of
FGF23 are associated with an increased risk of major cardiovascular
events.
Safety
Tenapanor was well tolerated. Only 4.3% of patients in the
tenapanor arm discontinued treatment compared to 2.5% in the binder
arm. The single adverse event with a placebo-adjusted rate greater
than 3% was loose stools/diarrhea at 36%, where most incidents were
reported within the first five days of treatment, were transient in
nature and the median time to resolution was four days after onset.
Notably, only 2.6% of patients in the tenapanor arm
discontinued treatment due to loose stools/diarrhea, as
compared to 0.8% in the binder arm. There were no serious adverse
events related to tenapanor.
About AMPLIFY
AMPLIFY, a double-blind,
placebo-controlled, randomized study, enrolled a total of 236
patients with CKD on dialysis, who despite a stable phosphate
binder regimen, had a serum phosphorus level greater than or equal
to 5.5 mg/dL and less than or equal to 10.0 mg/dL at screening.
After a run-in of two to four weeks, patients were randomized 1:1
to receive tenapanor or placebo twice daily while continuing their
established phosphate binder regimen. Baseline serum phosphorus at
randomization was at a mean level of 6.8 mg/dL. Tenapanor was
initiated at a starting dose of 30 mg twice daily with tenapanor
dose adjustments allowed based on serum phosphorus level and
gastrointestinal tolerability.
The primary endpoint of the study was the comparison of the
change from baseline in serum phosphorus levels at week four
between the tenapanor and binder arms. The key secondary endpoints
included a comparison of the proportion of patients achieving a
serum phosphorus level below 5.5 mg/dL at week four and relative
change from baseline in FGF23 levels between the tenapanor and
binder arms at week four. (NCT 03824587)
About Tenapanor for Hyperphosphatemia
Tenapanor,
discovered and developed by Ardelyx, is a first-in-class,
proprietary, 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, if approved,
tenapanor will be easier than phosphate binders for patients to
take with a regimen of just one small pill, taken twice daily. The
company previously reported results from its first Phase 3
monotherapy study with tenapanor in CKD patients on dialysis,
reporting that the primary endpoint was met (p=0.01) and that 50%
of patients (n=164) experienced a mean serum phosphorus reduction
of 2.56 mg/dL.
Ardelyx believes that, if approved, tenapanor can become a
foundational therapy for all CKD patients on dialysis who
experience elevated serum phosphorus.
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
common 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 over time (Spherix 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 dialysis patients (Block 2004), and common treatment goals are
to manage serum phosphorus levels to <5.5mg/dL.
About Fibroblast Growth Factor 23
(FGF23)
FGF23 is a protein in humans that is
responsible for phosphate and vitamin D metabolism. Prospective
clinical studies have demonstrated a linear association between
elevated levels of FGF23 and a greater risk of major cardiovascular
events and mortality. FGF23 is independently associated with
greater left ventricular mass and greater prevalence of left
ventricular hypertrophy (Amaral 2012).
Conference Call Information
The company will host a
conference call today, September 3,
2019 at 8:30AM ET to discuss
the AMPLIFY findings. To participate in the conference call, please
call (855) 296-9612 (toll-free) or (920) 663-6277 (toll) and
reference call ID number 9789472. A webcast of the call 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 lives of people with cardiorenal diseases by developing
first-in-class medicines that matter. Ardelyx's cardiorenal
pipeline includes the Phase 3 development of tenapanor for the
treatment of hyperphosphatemia in people with CKD 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 completed Phase 3 development of tenapanor for the
treatment of irritable bowel syndrome with constipation (IBS-C) and
submitted a new drug application, or NDA, to the U.S. Food and Drug
Administration, or FDA, for the treatment of patients with IBS-C
which has been granted a target action date under the Prescription
Drug User Fee Act (PDUFA) of September 12,
2019. 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 Co., Ltd. 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 in combination with
phosphate binders for the treatment of hyperphosphatemia, the
potential for tenapanor in combination with phosphate binders to
achieve serum phosphorus levels of less than 5.5mg/dL, Ardelyx's
expected timing for receipt of data from PHREEDOM, its ongoing
Phase 3 clinical trial evaluating tenapanor as monotherapy for the
treatment of hyperphosphatemia in CKD patients on dialysis,
Ardelyx's expectations regarding its plans for the
commercialization of tenapanor, Ardelyx's expectations regarding
the size of the patient populations for its product candidates, and
Ardelyx's expectations regarding the potential for tenapanor to
become a foundational therapy for all patients on dialysis who
experience elevated serum phosphorus. 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
August 9, 2019, and its future
current and periodic reports to be filed with the Securities and
Exchange Commission.
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