FREMONT, Calif., May 19, 2015 /PRNewswire/ -- Ardelyx, Inc.
(NASDAQ: ARDX), a clinical-stage biopharmaceutical company focused
on cardio-renal, gastrointestinal, and metabolic diseases, today
presented Phase 2b clinical trial results that demonstrated
statistically significant and clinically meaningful improvement in
IBS-C symptoms for tenapanor-treated patients compared to patients
receiving placebo. As previously reported, at the 50 mg dose of
tenapanor, the study met its primary efficacy endpoint of an
increase in the complete spontaneous bowel movement (CSBM)
responder rate. Most secondary endpoints, including abdominal pain
and other abdominal and IBS-C symptoms, demonstrated clinically
meaningful improvements. Tenapanor was well-tolerated, and the
safety results were consistent with those observed in previous
tenapanor trials.
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The findings were presented today in an oral presentation
entitled, "Efficacy and Safety of Tenapanor in Patients with
Constipation Predominant Irritable Bowel Syndrome: A 12-Week,
Double-Blind, Placebo-Controlled, Randomized Phase 2b Trial" at
the Digestive Disease Week (DDW) 2015 conference being held in
Washington, D.C. from May 16-19, 2015.
"IBS-C impacts the quality of life of millions of patients yet
is still one of the most enigmatic diseases of the gut," said
William Chey, MD, Professor of
Internal Medicine at University of
Michigan. "Tenapanor, if successfully developed, would
represent an entirely new mechanism of action for the treatment of
IBS-C that could give patients important options for their
disease."
"More than 14 million people worldwide are estimated to suffer
from IBS-C, many of whom are not effectively treated by current
marketed therapies," said Mike Raab,
President & Chief Executive Officer of Ardelyx. "Based on
tenapanor's clinical results through the Phase 2b program, we
believe that it has the potential to offer a best-in-class
treatment for this underserved population."
Phase 2b Clinical Trials for Tenapanor in IBS-C
The Phase 2b clinical trial was a randomized, double blind,
placebo-controlled, multi-center study to evaluate the safety and
efficacy of three dose levels of tenapanor in 356 subjects with
IBS-C as defined by the Rome III criteria and who had active
disease as determined during a two-week screening period. Subjects
who qualified and who were randomized into the study received 5,
20, or 50 mg of tenapanor or placebo twice daily for 12 consecutive
weeks. At the end of this treatment period, subjects were followed
for an additional 4 weeks. The primary endpoint, overall CSBM
responder rate, was achieved in 60.7 percent of patients receiving
tenapanor 50 mg twice daily versus 33.7 percent receiving placebo
(p < 0.001). A responder was defined as a patient who had
an increase of greater than or equal to one CSBM from baseline
during 6 out of 12 weeks. The results are reported on an
intent-to-treat basis.
The overall abdominal pain responder rate was achieved in 65.5
percent of patients receiving tenapanor 50 mg twice daily versus
48.3 percent receiving placebo (p = 0.026). An overall
abdominal pain responder was defined as a patient who experienced
at least a 30 percent decrease in abdominal pain from baseline for
6 of 12 weeks.
The overall responder rate, or dual composite endpoint percent,
was achieved in 50.0 percent of patients receiving tenapanor 50 mg
twice daily versus 23.6 percent receiving placebo (p <
0.001). An overall responder was defined as a patient who was
both an overall CSBM responder and an overall abdominal pain
responder in the same week for 6 of 12 weeks.
As shown in the table, other key secondary endpoints that
exhibited significant improvements for patients receiving 50 mg
tenapanor twice daily compared to placebo-treated patients included
abdominal discomfort, abdominal bloating, straining, stool
consistency, CSBM per week and SBM per week.
Phase 2b Primary and Key Secondary Endpoints
Endpoint
|
Placebo
|
Tenapanor 50mg
twice daily
|
p-value
|
Primary Endpoint:
responder analysis ≥6 of 12 weeks*
|
≥1 CSBM
increase
|
33.7%
|
60.7%
|
p<0.001
|
Secondary Endpoints:
responder analysis ≥6 of 12 weeks*
|
≥30% abdominal pain
reduction
|
48.3%
|
65.5%
|
p=0.026
|
≥30% abdominal pain
reduction and ≥1 CSBM increase in same week
|
23.6%
|
50.0%
|
P<0.001
|
Secondary Endpoints:
LS mean change from baseline to week 12**
|
Abdominal pain
(0-10)
|
-2.3
|
-3.1
|
P=0.014
|
Abdominal discomfort
(0-10)
|
-2.0
|
-3.0
|
P=0.004
|
Abdominal bloating
(0-10)
|
-1.6
|
-2.6
|
P=0.023
|
Straining
(0-5)
|
-0.7
|
-1.2
|
P=0.006
|
Stool consistency
BSFS***
|
1.0
|
2.2
|
P<0.001
|
CSBM/week
|
0.9
|
2.7
|
P<0.001
|
SBM/week
|
1.6
|
3.4
|
P=0.006
|
|
* P-value uses
Cochran-Mantel-Haenszel analysis
|
|
** P-Value Uses
Analysis of covariance analysis
|
|
*** BSFS is the
Bristol Stool Form Scale with 1 = hard and 7 = watery
|
A dose response relationship among all doses was observed in the
primary endpoint, as well as in most secondary endpoints, although
statistical significance was not achieved at the 5 mg or 20 mg
doses. Additionally, the activity of tenapanor was maintained
throughout the entire 12-week treatment period.
Tenapanor was well-tolerated in these patients, and the safety
results were consistent with those observed in previous tenapanor
trials. The most common adverse events at 50 mg twice daily
(greater than or equal to 5 percent) that occurred more frequently
in tenapanor-treated patients compared to placebo-treated patients
were diarrhea at 11.2 percent vs. 0 percent, and urinary tract
infections at 5.6 percent vs. 4.4 percent. Overall rates of
discontinuation due to adverse events were 4.5 percent (3.3 percent
due to diarrhea) for the tenapanor-treated patients (50 mg twice
daily) and 3.3 percent for the placebo-treated patients.
Based on the analysis of plasma samples tested as part of the
study, the minimally systemic nature of tenapanor was
confirmed.
The abstract for oral presentation is available in
Gastroenterology, Vol. 148, Issue 4, S-191–S-192, 2015.
Please refer to Ardelyx's website for a copy of the DDW slide
presentation at http://ir.ardelyx.com.
Ardelyx formed a partnership with AstraZeneca in October 2012 to develop and commercialize
tenapanor. Under the terms of the agreement, AstraZeneca is
obligated to communicate to Ardelyx, on or before June 29, 2015, whether it will continue the
development of tenapanor. Should AstraZeneca decide to pursue
the development of only the IBS-C indication, Ardelyx will be
entitled to a milestone payment of $10
million. Should AstraZeneca decide to pursue the development
of any other indication or multiple indications, Ardelyx will be
entitled to receive a $20 million
milestone payment. Ardelyx is scheduled for an end of phase 2
meeting with the FDA scheduled in June. If AstraZeneca decides to
return the program to Ardelyx, the Company seeks to be in a
position to initiate a Phase 3 clinical program for tenapanor in
IBS-C in the fourth quarter of 2015.
About Irritable Bowel Syndrome with Constipation
(IBS-C)
IBS-C is a gastrointestinal disorder in which
abdominal pain or discomfort is associated with constipation,
significantly affecting health and quality of life. It is unknown
what causes IBS-C. There is no specific test or biomarker for IBS-C
and therefore, its presence is diagnosed by symptoms and by
eliminating other disorders. IBS-C is very similar to chronic
constipation but is clinically distinguished by its significant
pain component.
Based on reports in the literature regarding the prevalence of
IBS in the U.S. population and the percentage of individuals who
have IBS-C as opposed to other forms of IBS, Ardelyx estimates that
approximately 1.4 percent of the U.S. population has IBS-C, or
about 4.4 million individuals. Of those, approximately 1.0 million
patients have been diagnosed with IBS-C. Additionally, there are
about 6.6 million IBS-C patients in Europe and about 3.4 million in Japan.
About Ardelyx, Inc.
Ardelyx is a clinical-stage biopharmaceutical company focused on
the discovery, development and commercialization of innovative,
minimally-systemic, small molecule therapeutics that work
exclusively in the gastrointestinal tract to treat cardio-renal,
gastrointestinal and metabolic diseases. Ardelyx has developed a
proprietary drug discovery and design platform enabling it, in a
rapid and cost-efficient manner, to discover and design novel drug
candidates. Utilizing this platform, the Company has discovered and
designed tenapanor. Ardelyx formed a partnership with
AstraZeneca in October 2012 to
develop and commercialize tenapanor. In addition to
tenapanor, Ardelyx has discovered small molecule NaP2b inhibitors
for the treatment of hyperphosphatemia in patients on dialysis, a
program licensed to Sanofi, and independently is advancing several
additional research programs focused in cardio-renal,
gastrointestinal and metabolic diseases. Ardelyx is located in
Fremont, California. For more
information, please visit Ardelyx's website at www.ardelyx.com
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 statements
regarding the potential for tenapanor in treating IBS-C patients,
the timing of AstraZeneca's decisions regarding its future plans
for tenapanor, the potential receipt and timing of milestone
payments from AstraZeneca in connection with any decision by it to
continue the development of tenapanor and our future development
plans and the timing thereof, if the rights to tenapanor are
returned to us. Such forward-looking statements involve
substantial risks and uncertainties that could cause the
development of tenapanor, 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, AstraZeneca's right under the
license agreement to choose which indication or indications for
which tenapanor will be developed, and AstraZeneca's right under
the license agreement to terminate the agreement upon written
notice to Ardelyx. 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 filed on Form
10-Q with the Securities and Exchange Commission on May 12, 2015.
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