FREMONT, Calif., Oct. 11, 2017 /PRNewswire/ -- Ardelyx, Inc.
(NASDAQ: ARDX) today reported positive results from T3MPO-2, its
second Phase 3 study of tenapanor for irritable bowel syndrome with
constipation (IBS-C). The study hit statistical significance for
the primary endpoint and all secondary endpoints evaluated for the
topline results and demonstrated the ability to normalize bowel
movements. The primary endpoint, the combined responder rate for
six of 12 weeks, showed that a greater proportion of
tenapanor-treated patients compared to placebo-treated patients
(36.5% vs. 23.7%, p<0.001) had at least a 30 percent reduction
in abdominal pain and an increase of one or more complete
spontaneous bowel movements (CSBM) in the same week for at least
six of the 12 weeks of the treatment period. In addition, tenapanor
achieved statistical significance for the CSBM and abdominal pain
responder rates in the six of 12 and nine of 12-treatment weeks,
with a consistent response across the 26 weeks of the study.
Tenapanor was well-tolerated in treated patients.
"These results are a game-changer for patients with IBS-C, their
treating physicians and for Ardelyx as a company," said
Mike Raab, president and chief
executive officer of Ardelyx. "They demonstrate the significant
benefit tenapanor can have for patients with IBS-C, importantly,
leading to a normalization of bowel movements for many patients.
These results show that tenapanor has significant potential in the
market and bolsters our commitment to identify the ideal
collaboration partner to help ensure that we reach the most
patients possible who would benefit from therapy."
"IBS-C is a highly burdensome and difficult-to-treat condition
affecting more than 11 million people in the United States, and often preventing them
from engaging in day-to-day activities, such as going to work,
exercising and even meeting socially with family and friends," said
William Chey, M.D., University of Michigan. "Based on tenapanor's
unique mechanism of action, which relies upon the inhibition of
sodium absorption, and the exciting data reported today, tenapanor
has the potential to be an important advancement and a new
treatment option for patients suffering from IBS-C."
T3MPO-2 Trial Design
T3MPO-2 is a 26-week,
double-blind, placebo-controlled, multi-center, randomized trial.
The trial was conducted in a total of 593 patients meeting the
ROME III criteria for the
diagnosis of IBS-C. Patients were randomized one-to-one to receive
either 50 mg of tenapanor (n=293) or placebo (n=300) twice-daily.
The trial included a two-week screening period, during which
patients with active disease, based on bowel movement frequency and
abdominal pain score recorded in a daily phone diary, were
randomized into the trial.
T3MPO-2 Top-line Efficacy Results
During the two-week
screening period, the baseline scores were well-balanced between
the tenapanor and placebo groups. The mean weekly CSBMs were 0.11
and the mean abdominal pain score was 6.26 (on a 0 - 10 scale where
0 was no pain and 10 was very severe). Key data are as follows:
Table
1
|
6 of 12 Treatment
Week Results
|
Tenapanor
|
Placebo
|
P
value
|
Combined responder
(primary endpoint) (abdominal pain and CSBM
responder)
|
36.5%
|
23.7%
|
p<0.001
|
CSBM
responder (increase ≥ 1 CSBM from baseline)
|
47.4%
|
33.3%
|
p<0.001
|
Abdominal pain
responder (≥ 30% abdominal pain reduction)
|
49.8%
|
38.3%
|
p=0.004
|
Table
2
|
9 of 12 Treatment
Week Results
|
Tenapanor
|
Placebo
|
P
value
|
Combined
responder (abdominal pain and CSBM responder)
|
18.4%
|
5.3%
|
p<0.001
|
CSBM
responder (increase ≥ 1 CSBM from baseline and ≥3
CSBM/week)
|
22.2%
|
6.0%
|
p<0.001
|
Abdominal pain
responder (≥ 30% abdominal pain reduction)
|
35.8%
|
26.7%
|
p=0.015
|
Table
3
|
Durable Responder
Results (9 of 12 and >3 of last 4 treatment
weeks)
|
Tenapanor
|
Placebo
|
P
value
|
Combined
responder (abdominal pain and CSBM responder)
|
18.1%
|
5.0%
|
p<0.001
|
CSBM
responder (increase ≥ 1 CSBM from baseline and ≥3
CSBM/week)
|
21.2%
|
5.7%
|
p<0.001
|
Abdominal pain
responder (≥ 30% abdominal pain reduction)
|
34.8%
|
26.7%
|
p=0.028
|
T3MPO-2 Safety Results
Tenapanor was well-tolerated,
consistent with the experience across previous clinical trials. The
only adverse events observed in more than two percent of patients
in the tenapanor-treated group that were also greater than placebo
were diarrhea (16.0% vs. 3.7%), flatulence (3.1% vs. 1.0%),
nasopharyngitis (4.4% vs. 3.7%) and abdominal distension (3.4% vs.
0.3%). The placebo adjusted discontinuation rate due to diarrhea
was 5.8 percent.
Based on positive results from two positive Phase 3 trials,
Ardelyx is on track to submit a New Drug Application (NDA) to the
U.S. Food and Drug Administration for tenapanor for the treatment
of IBS-C in the second half of 2018. Final, detailed results from
the study are expected to be presented at a medical meeting in
2018.
T3MPO-3
Patients who have completed T3MPO-1 and
T3MPO-2 are eligible to enter T3MPO-3, Ardelyx's open-label,
long-term safety trial where patients can continue to receive
tenapanor for up to one year. T3MPO-3 is fully enrolled and
expected to conclude in late 2017. The results of the trial will be
included in the NDA submission for tenapanor for the treatment of
patients with IBS-C.
T3MPO-2 Primary and Secondary Endpoint Definitions
Primary Endpoint:
- Combined responder rate (6/12 week): A six of 12-week combined
responder is a CSBM responder and an abdominal pain responder
during the same week for six of 12 weeks.
Secondary Endpoints:
- CSBM responder rate (6/12 week): A six of 12-week CSBM
responder is a patient that has an increase of at least one CSBM
from baseline during a week for six of 12 weeks.
- Abdominal pain responder rate (6/12 week): A six of 12-week
abdominal pain responder is a patient that has at least a 30
percent decrease in abdominal pain from baseline during a week for
six of 12 weeks.
- Combined responder rate (9/12 week): A nine of 12-week combined
responder is a nine of 12 week CSBM responder and an abdominal pain
responder during the same week for nine of 12 weeks.
- CSBM responder rate (9/12 week): A nine of 12-week CSBM
responder is a patient that has an increase of at least one CSBM
from baseline and at least three CSBMs during a week for nine of 12
weeks. Normal bowel function is characterized by at least three
bowel movements a week up to three bowel movements a day.
- Abdominal pain responder rate (9/12 week): A nine of 12-week
abdominal pain responder is a patient that has at least a 30
percent decrease in abdominal pain from baseline during a week for
nine of 12 weeks.
- Durable responder rates (9/12 week): All three durable
responder endpoints – combined responder rate, CSBM responder rate
and abdominal pain responder rate – are identical to the nine
of 12-week responder endpoints, except the response must also occur
in three of the last four treatment period weeks.
Conference Call Information
The company will host a
conference call today, October 11,
2017 at 4:30 p.m. ET to
discuss the T3MPO-2 results. To participate in the conference call,
please dial (855) 296-9612 (toll-free) or (920) 663-6277 (toll) and
reference call ID number 98932908. A webcast of the call and
reference slides that will be used during the call, can 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 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 a late-stage company
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; Ardelyx's expectations
regarding the timing for the completion of T3MPO-3; Ardelyx's
expectations regarding the filing of an NDA for tenapanor for the
treatment of IBS-C; and Ardelyx's ability to establish
collaboration partnerships in the future. 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. 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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