FREMONT, Calif., May 12, 2017 /PRNewswire/ -- Ardelyx, Inc.
(NASDAQ: ARDX), a late-stage clinical company focused on enhancing
the treatment of patients with cardiorenal and gastrointestinal
(GI) diseases, today reported positive, topline results from the
T3MPO-1 trial, the first of two Phase 3 trials evaluating tenapanor
for the treatment of patients with irritable bowel syndrome with
constipation (IBS-C). Tenapanor is Ardelyx's investigational,
minimally systemic, small-molecule NHE3 inhibitor.
The T3MPO-1 trial achieved statistical significance for the
primary endpoint and seven of eight secondary endpoints. 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 (27.0% vs 18.7%, p=0.02) 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.
Tenapanor was well-tolerated, consistent with the experience across
previous clinical trials.
"We're pleased to have achieved the primary endpoint in the
T3MPO-1 trial," said Mike Raab,
president and chief executive officer of Ardelyx. "IBS-C is an
extremely difficult, life-altering condition, and despite
advancements, there remains a strong need for new, innovative
treatments. In this trial, tenapanor demonstrated clinical activity
across a large number of study parameters and had a favorable
safety profile consistent with previous clinical experience. With a
differentiated mechanism of action, we believe tenapanor has the
potential to augment the care of patients with IBS-C."
T3MPO-1 Trial Design
T3MPO-1 was a 12-week,
double-blind, placebo-controlled, multi-center, randomized trial
with a four-week, randomized withdrawal period conducted in a total
of 610 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=309) or
placebo (n=301) 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-1 Topline Efficacy Results
During the two-week
screening period, the baseline mean weekly CSBMs were 0.2 and the
mean abdominal pain score was 6.3 (on a 0 - 10 scale where 0 is no
pain and 10 is 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)
|
27.0%
|
18.7%
|
p=0.02
|
CSBM
responder
(increase ≥ 1 CSBM from
baseline)
|
33.9%
|
29.4%
|
p=0.27
|
Abdominal pain
responder (≥ 30% abdominal pain
reduction)
|
44.0%
|
33.1%
|
p=0.008
|
|
Table
2
|
9 of 12 Treatment
Week Results
|
Tenapanor
|
Placebo
|
P
value
|
Combined
responder
(abdominal pain and CSBM
responder)
|
13.7%
|
3.3%
|
p<0.001
|
CSBM
responder
(increase ≥ 1 CSBM from baseline and ≥3
CSBM/week)
|
16.9%
|
5.0%
|
p<0.001
|
Abdominal pain
responder
(≥ 30% abdominal pain
reduction)
|
30.3%
|
19.4%
|
p=0.003
|
|
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)
|
13.0%
|
3.3%
|
p<0.001
|
CSBM
responder
(increase ≥ 1 CSBM from baseline and ≥3
CSBM/week)
|
16.0%
|
4.7%
|
p<0.001
|
Abdominal pain
responder
(≥ 30% abdominal pain
reduction)
|
29.3%
|
19.4%
|
p=0.006
|
"When we look at the totality of the topline results from
T3MPO-1, we believe tenapanor has the potential to offer benefit to
patients with IBS-C," said David
Rosenbaum, Ph.D., chief development officer of Ardelyx. "We
are encouraged that the nine of 12 week data demonstrate a durable
and sustained response for constipation and abdominal pain, as well
as a normalization of bowel movement frequency, for many patients.
The individual CSBM responder rate from the six of 12 week analysis
was the one secondary endpoint not met and those data are not
consistent with the results from our previous clinical studies. We
plan to assess these data alongside the results from T3MPO-2, our
six-month Phase 3 study, to evaluate the total benefit that
tenapanor may provide to patients with this extremely challenging
condition."
T3MPO-1 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
treated with tenapanor, as compared with placebo, were diarrhea
(14.6% vs 1.7%) and nausea (2.6% vs 1.7%). Discontinuations due to
diarrhea were 5.9 percent for the tenapanor-treated patients,
compared to 0.6 percent for the placebo group, based on the
preliminary results.
T3MPO-2 and T3MPO-3
A second Phase 3 trial, T3MPO-2, a
26-week study evaluating tenapanor for the treatment of patients
with IBS-C is ongoing with data expected early in the fourth
quarter of 2017. 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 expected to conclude in late 2017.
T3MPO-1 Primary and Key Secondary Endpoint
Definitions
- 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.
- 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 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.
- 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 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, May 12, 2017
at 8:30 a.m. ET to discuss the
T3MPO-1 findings. To participate in the conference call, please
call (855)-296-9612 (toll-free) or (920)- 663-6277 (toll) and
reference call ID number 23050169. 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 Tenapanor for IBS-C
Tenapanor, invented and
developed internally by scientists at Ardelyx, is a first-in-class,
proprietary, oral, experimental medication that works primarily in
the gut and is 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 GI tract to reduce the
absorption of dietary sodium into the blood stream. 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, which loosens stool, helping to relieve constipation. We have
also seen a desired benefit in the abdominal pain component of
IBS-C in our studies to-date. The mechanism of abdominal pain is
currently under investigation to be detailed in future
manuscripts.
About IBS-C
Irritable bowel syndrome with
constipation, or IBS-C, is a gastrointestinal disorder
characterized by significant abdominal pain and constipation (when
a bowel movement is difficult due to insufficient/decreased amount
of fluid in the GI, or happens less often than normal). 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, and there are
currently no specific diagnostic tests or biomarkers for detection.
Therefore, IBS-C is diagnosed by symptoms and by eliminating other
disorders. IBS-C is similar to chronic constipation but is
clinically distinct as a result of the significant abdominal pain
component.
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, a TGR5 agonist approaching Phase 1 development. Leveraging
the company's platform and unique gut-restriction chemistry,
Ardelyx intends to build a fully integrated, revenue-generating
biopharmaceutical company with leading cardiorenal and GI business
portfolios. For more information, please visit 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 IBS-C patients; Ardelyx's future development
plans for tenapanor and its other product candidates and the
expected timing thereof; Ardelyx's expected timing for the receipt
of results from the T3MPO-2 and T3MPO-3 clinical trials evaluating
tenapanor in IBS-C; 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 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 and the
uncertainties in the manufacture of clinical trial material,
including process development, including the regulatory approval ,
the uncertainties in the manufacture of clinical trial material,
including process development, and uncertainties in the drug
commercialization 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 May 5, 2017, and its future current and periodic
reports to be filed with the Securities and Exchange
Commission.
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SOURCE Ardelyx