FREMONT, Calif., Oct. 16, 2017 /PRNewswire/ -- Ardelyx, Inc.
(NASDAQ: ARDX) today reported that data from preclinical studies
have shown that tenapanor works to reduce abdominal pain caused by
irritable bowel syndrome with constipation (IBS-C) through the
inhibition of TRPV-1 dependent signaling. TRPV-1, better known as
the "hot chili pepper receptor," is a well-established pain target
known for transmitting painful stimuli from a variety of sources
including heat, protons and inflammatory molecules. Tenapanor,
Ardelyx's investigational, minimally systemic, small-molecule
inhibitor of NHE3, has demonstrated statistically significant
results in two positive Phase 3 studies in patients with IBS-C, and
the ability to reduce abdominal pain and alleviate
constipation.
The preclinical data on tenapanor's pain mechanism are being
presented by investigators from the Johns
Hopkins University School of Medicine in a poster session on
Tuesday, October 17, 2017 at the
American College of Gastroenterology (ACG) World Congress 2017. The
congress is being held October 13 –
18, 2017 in Orlando, Florida.
These preclinical data were generated at Dr. Jay Pasricha's laboratory at Johns Hopkins University School of Medicine under a
sponsored research agreement with Ardelyx. Using an established
rodent model of IBS-like colonic hypersensitivity, the results show
that tenapanor treatment reduced visceral hypersensitivity (pain in
the internal organs) and normalized colonic sensory neuronal
excitability and TRPV-1 currents. Treatment with tenapanor also
increased stool excretion and stool water content. Tenapanor had a
significantly better effect on visceral hypersensitivity than
placebo or PEG, a well-known laxative not known to have an
analgesic effect.
"This may be a critical aspect of tenapanor's therapeutic
mechanism for IBS-C patients. This work links tenapanor's ability
to improve the symptoms of visceral hypersensitivity and abdominal
pain, two of the most important and burdensome symptoms for
patients with IBS-C, to a well-established pain target. These
experiments have demonstrated that tenapanor inhibits TRPV-1
dependent pain signaling in neurons lining the GI tract," said
Jeremy Caldwell, Ph.D., chief
scientific officer of Ardelyx. "Based on this research, tenapanor
influences TRPV-1 indirectly, which we plan to further investigate
to fully elucidate this first-in-class mechanism of action. To the
best of our knowledge, tenapanor is the only potential treatment
option for IBS-C that has shown the ability to reduce abdominal
pain through inhibition of TRPV-1 signaling, representing a
completely novel therapeutic option for these patients."
"The findings related to tenapanor's mechanism of action further
support the positive Phase 3 IBS-C results that we have reported
throughout 2017, including the exciting data from our second IBS-C
Phase 3 study, T3PMO-2, which we reported last week," said
David Rosenbaum, Ph.D., chief
development officer of Ardelyx. "Our T3MPO program is nearing
completion, and we are moving forward to submit our first New Drug
Application to the U.S. Food and Drug Administration for this
indication in the second half of 2018. With the combination of
tenapanor's first-in-class mechanism and its demonstrated ability
to reduce pain and alleviate constipation, we believe tenapanor
represents a significant new treatment approach for physicians and
patients."
In addition to the poster session, Bill
Chey, M.D., a principal investigator in the T3MPO clinical
program, will present detailed data from Ardelyx's first, positive
Phase 3 study, T3MPO-1, evaluating tenapanor for the treatment of
people with IBS-C, which were originally announced in May 2017. The data will be presented in an oral
session at the meeting on Tuesday, October
17, 2017 at 2:40 p.m.
About Tenapanor
Tenapanor, invented and developed by
scientists at Ardelyx, is a first-in-class, proprietary, minimally
absorbed, oral, experimental medication in late-stage clinical
development. It has a unique mechanism of action that, in IBS-C,
acts by inhibiting, or blocking, the NHE3 transporter in the
gastrointestinal (GI) tract to reduce the absorption of dietary
sodium. Blocking NHE3 results in an increase in the amount of
sodium in the gut. This increased sodium in the gut leads to an
increase of fluid in the gut, loosening stool and helping to
relieve constipation. We have also seen a desired benefit in the
abdominal pain component of IBS-C in our studies to-date.
Tenapanor is also in Phase 3 development for the treatment of
hyperphosphatemia in patients with end-stage renal disease who are
on dialysis. In hyperphosphatemia, tenapanor blocks the NHE3 sodium
transporter in the GI tract, reducing the absorption of dietary
sodium and resulting in increased protons within the cells. The
increase in protons causes a preferential reduction in phosphate
uptake by tightening junctions or pores that regulate phosphate
absorption in the GI tract. We have not observed this impact on
other ions, nutrients or macromolecules in our clinical trials,
suggesting that this effect is preferential for phosphate.
About IBS-C
Irritable bowel syndrome with
constipation, or IBS-C, is a gastrointestinal disorder
characterized by significant abdominal pain and constipation.
Ardelyx estimates that approximately 11 million people in
the United States suffer from
IBS-C. This condition significantly impacts the health and quality
of life of affected patients. The cause of IBS-C is unknown.
About Ardelyx, Inc.
Ardelyx is focused on enhancing
the way patients with cardiorenal and gastrointestinal (GI)
diseases are treated by using the gut as the gateway to delivering
medicines that matter. The company has established unique
cardiorenal and GI business portfolios aimed at bringing new,
effective medicines with distinct safety and dosing advantages to
underserved patients. Ardelyx's cardiorenal portfolio includes the
Phase 3 development of tenapanor for the treatment of
hyperphosphatemia in people with end-stage renal disease who are on
dialysis and the Phase 3 development of RDX7675 for the treatment
of people with hyperkalemia. The company's GI portfolio includes
the Phase 3 development of tenapanor for the treatment of people
with irritable bowel syndrome with constipation (IBS-C), and
RDX8940, the company's TGR5 agonist. 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
tenapanor in treating patients with IBS-C, including tenapanor's
ability to reduce pain in IBS-C patients by inhibiting TRPV-1
signaling; and Ardelyx's expectations regarding the timing of
the completion of its T3MPO program and the timing of its
submission of an NDA for tenapanor for the treatment of IBS-C
patients; 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
research and 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, 2017, and its future current and
periodic reports to be filed with the Securities and Exchange
Commission.
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