FREMONT, Calif., Sept. 12, 2019 /PRNewswire/ -- Ardelyx, Inc.
(NASDAQ: ARDX), a specialized biopharmaceutical company focused on
developing innovative first-in-class medicines to improve treatment
for people with cardiorenal diseases, today announced that the U.S.
Food and Drug Administration has approved IBSRELA®
(tenapanor), a 50 mg, twice daily oral pill for the treatment of
irritable bowel syndrome with constipation (IBS-C) in adults.
IBSRELA is a minimally-absorbed small molecule that acts locally in
the gastrointestinal (GI) tract to inhibit the sodium-hydrogen
exchanger NHE3, resulting in an increase in bowel movements and a
decrease in abdominal pain for IBS-C patients.
"IBSRELA has the potential to provide IBS-C patients and their
doctors with a novel mechanism and an innovative approach to
managing IBS-C, a highly burdensome and difficult-to-treat
condition affecting more than 11 million people in the United States," commented Mike Raab, president and chief executive officer
of Ardelyx. "This approval is an extremely important and
rewarding milestone for Ardelyx, and represents the culmination of
years of dedication to advancing our discoveries and medicines in
an effective and rigorous manner. We look forward to establishing a
commercial collaboration with a partner that has the capabilities
to drive the successful launch and marketing of IBSRELA in this
large and underserved IBS-C patient population."
Mr. Raab continued, "With the approval of IBSRELA for IBS-C,
along with the successful completion of our AMPLIFY trial in
hyperphosphatemia, we've delivered on two major corporate
milestones in the last two weeks due to flawless execution by the
remarkable and talented team at Ardelyx. With these milestones
accomplished, and the PHREEDOM trial reading out in Q4, I have
great confidence that we are well positioned to file our NDA for
hyperphosphatemia next year with potential approval and launch in
2021. We are excited about this next chapter for Ardelyx as we
begin the development of our playbook for launch and
commercialization of tenapanor for hyperphosphatemia in chronic
kidney disease patients on dialysis and are excited to begin
sharing more of our vision in the coming months."
IBSRELA (tenapanor) Phase 3 IBS-C
Program
Phase 3 Study Designs
The Phase 3 IBS-C program included two randomized, double-blind,
placebo-controlled trials. The trial designs were identical through
the first 12 weeks of treatment, and thereafter differed in that
Trial 1 (NCT02686138) continued for an additional 14 weeks of
treatment (26 weeks double-blind treatment), whereas Trial 2
(NCT02621892) included a 4-week randomized withdrawal (RW)
period (12 weeks double-blind treatment). Patients who were
enrolled in these trials met the Rome III criteria for IBS-C,
related to abdominal pain and bowel movement frequency.
Primary Endpoint
The primary endpoint for both trials was the proportion of patients
who were responders during the 12-week treatment period. A
responder, as defined by the FDA, was a patient who experienced at
least a 30% reduction in the weekly average abdominal pain score
compared with baseline and an increase of at least 1 complete
spontaneous bowel movement (CSBM) in weekly average from baseline,
in the same week, for at least 6 of the first 12 treatment
weeks.
Results
In both Phase 3 IBS-C trials, IBSRELA met the primary endpoint as
compared with placebo (Trial 1: 37% versus 24%, IBSRELA versus
placebo, respectively. Trial 2: 27% versus 19% IBSRELA versus
placebo, respectively).
In Trials 1 and 2, the proportion of responders for 9 out of the
first 12 weeks, including at least 3 of the last 4 weeks, was
greater in IBSRELA-treated patients compared to placebo-treated
patients. In addition, in Trial 1, the proportion of
responders for 13 out of 26 weeks was greater in IBSRELA‑treated
patients compared to placebo-treated patients. In both
trials, improvements from baseline in average weekly CSBMs and
abdominal pain were observed by Week 1, with improvement maintained
through the end of treatment.
In both studies, the most common adverse event was diarrhea (16%
with IBSRELA vs 4% with placebo in Trial 1; and 15% with IBSRELA vs
2% with placebo in Trial 2), with severe diarrhea reported in 2.5%
of IBSRELA-treated patients compared to 0.2% on placebo‑treated
patients during the 26 weeks of Trial 1 and the 12 weeks of Trial
2. Overall discontinuation rates were low among patients treated
with IBSRELA (7.6%) and placebo (0.8%) and the most common adverse
reaction leading to discontinuation was diarrhea (6.5% of
IBSRELA-treated patients compared to 0.7% of placebo-treated
patients).
Indications and Usage
IBSRELA (tenapanor) is indicated
for treatment of irritable bowel syndrome with
constipation (IBS-C) in adults.
IMPORTANT SAFETY INFORMATION
WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC
PATIENTS
IBSRELA is contraindicated in patients less
than 6 years of age; in young juvenile rats, tenapanor caused death
presumed to be due to dehydration. Avoid use of IBSRELA in patients
6 years to less than 12 years of age. The safety and
effectiveness of IBSRELA have not been established in pediatric
patients less than 18 years of age.
Contraindications
- IBSRELA is contraindicated in pediatric patients less than 6
years of age.
- IBSRELA is contraindicated in patients with known or suspected
mechanical gastrointestinal obstruction
Warnings and Precautions
Risk of Serious Dehydration in Pediatric Patients
IBSRELA is contraindicated in patients below 6 years of age. The
safety and effectiveness of IBSRELA in patients less than 18 years
of age have not been established. In young juvenile rats (less than
1 week old; approximate human age equivalent of less than 2 years
of age), decreased body weight and deaths occurred, presumed to be
due to dehydration, following oral administration of tenapanor.
There are no data available in older juvenile rats (human age
equivalent 2 years to less than 12 years).
Avoid the use of IBSRELA in patients 6 years to less than 12
years of age. Although there are no data in older juvenile rats,
given the deaths in younger rats and the lack of clinical safety
and efficacy data in pediatric patients, avoid the use of IBSRELA
in patients 6 years to less than 12 years of age
Diarrhea
Diarrhea was the most common adverse reaction in two randomized,
double-blind, placebo-controlled trials of IBS-C. Severe diarrhea
was reported in 2.5% of IBSRELA-treated patients. If severe
diarrhea occurs, suspend dosing and rehydrate patient.
Adverse Reactions
In the two IBS-C trials, the most common adverse reaction in
IBSRELA-treated patients (incidence ≥2% and greater than in
the placebo group) was diarrhea (Trial 1: 16% IBSRELA vs 4%
placebo; Trial 2: 15% IBSRELA vs 2% placebo).
Please also see the full Prescribing
Information, including Box Warning, for additional risk
information.
About Irritable Bowel Syndrome with Constipation
(IBS-C)
Irritable bowel syndrome with constipation (IBS-C)
is a GI disorder in which abdominal pain is associated with
constipation, and significantly affects the health and quality of
life of at least 11 million people in the US. A study published in
the American Journal of Gastroenterology in 2015 showed that over
50 percent of IBS-C patients rated their pain, constipation and
straining as being "extremely bothersome." In the same study, GI
symptoms led to an average 4.9 days of "disrupted productivity" and
0.8 days of missed work per month.
About IBSRELA for IBS-C
IBSRELA (tenapanor) is a
locally acting inhibitor of the sodium/hydrogen exchanger 3 (NHE3),
an antiporter expressed on the apical surface of the small
intestine and colon primarily responsible for the absorption of
dietary sodium. In vitro and animal studies indicate its major
metabolite, M1, is not active against NHE3. By inhibiting NHE3 on
the apical surface of the enterocytes, tenapanor reduces absorption
of sodium from the small intestine and colon, resulting in an
increase in water secretion into the intestinal lumen, which
accelerates intestinal transit time and results in a softer stool
consistency.
Tenapanor has also been shown to reduce abdominal pain by
decreasing visceral hypersensitivity and by decreasing intestinal
permeability in animal models. In rat model of colonic
hypersensitivity, tenapanor reduced visceral hyperalgesia and
normalized colonic sensory neuronal excitability.
Conference Call Information
The company will host a
conference call today, September 12,
2019 at 4:30PM ET to discuss
the approval of IBSRELA for the treatment of IBS-C. To participate
in the conference call, please call (855) 296-9612 (toll-free) or
(920) 663-6277 (toll) and reference call ID number 5897497. 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. On September 3, 2019, the company reported positive
data from AMPLIFY, a pivotal Phase 3 study investigating tenapanor
in a combination with phosphate binders in patients with chronic
kidney disease on dialysis whose hyperphosphatemia was not
previously controlled with binders alone. The study successfully
met the primary endpoint and all key secondary endpoints, including
demonstrating a statistically significant mean reduction in serum
phosphorus from baseline to the end of the treatment period. On
September 12, 2019, Ardelyx received
approval of IBSRELA (tenapanor) for the treatment of irritable
bowel syndrome with constipation (IBS-C). To efficiently bring its
treatments to market, Ardelyx is pursuing strategic collaborations
for IBSRELA for IBS-C and tenapanor for hyperphosphatemia in
certain territories. Ardelyx has established agreements with Kyowa
Kirin Company Limited 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 IBSRELA
in treating IBS-C patients, the potential for Ardelyx's product
candidates in treating the diseases and conditions for which they
are being developed, Ardelyx's ability to establish additional
collaborations, including a collaboration for the commercialization
of IBSRELA, Ardelyx's expectations regarding the size of the
patient populations for IBSRELA and for its product candidates,
Ardelyx's expected timing of its NDA filing for tenapanor for
hyperphosphatemia in CKD patients on dialysis, and Ardelyx's
current expectations regarding the potential commercialization of
tenapanor for hyperphosphatemia. 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, the uncertainties
associated with the regulatory approval process, 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
August 9, 2019, and its future
current and periodic reports to be filed with the Securities and
Exchange Commission.
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