CAMBRIDGE, Mass. & DUBLIN--(BUSINESS WIRE)--
Ironwood
Pharmaceuticals, Inc. (NASDAQ: IRWD) and Allergan
plc (NYSE: AGN) announced today the initiation of a Phase IIb
clinical trial evaluating two orally-administered colonic release
formulations of linaclotide in adult patients with irritable bowel
syndrome with constipation (IBS-C). The two formulations are being
evaluated together in this trial to support potential advancement of two
distinct product opportunities into late stage development, one for
patients with IBS-C who suffer from both abdominal pain and constipation
symptoms, and the other for patients suffering from other
gastrointestinal (GI) disorders with lower abdominal pain as a
predominant symptom. Data from the Phase IIb clinical trial in IBS-C are
expected in the second half of 2016.
Linaclotide is the first and only FDA-approved guanylate cyclase‐C
(GC‐C) agonist; it is approved as a 145 mcg capsule to be taken once per
day for the treatment of adults with chronic idiopathic constipation
(CIC) and as a 290 mcg capsule to be taken once per day for the
treatment of adults with IBS-C. Linaclotide binds to the GC-C receptor
in the intestine and is thought to work in two ways, based on
non-clinical studies: by decreasing the activity of pain-sensing nerves
and by increasing fluid secretion into the intestine. The
investigational linaclotide colonic release formulations are designed to
provide targeted delivery of linaclotide to the distal small intestine
and colon, and the companies believe this may further decrease the
activity of key pain-sensing nerves in the colon with a smaller increase
in fluid secretion.
"Abdominal pain is a key symptom of many gastrointestinal diseases,
including IBS-C. Millions of patients are impacted by abdominal pain,
and they have few prescription options," said David Nicholson, Ph.D.,
executive vice president of brand research and development at Allergan.
"Our goal in this trial is to evaluate the potential of our two
linaclotide colonic release formulations to provide enhanced abdominal
pain relief to patients suffering from IBS-C as well as to evaluate the
differences between the two formulations and inform a path forward for
developing a drug that can reduce gastrointestinal pain in other
disorders, such as other types of IBS, ulcerative colitis and
diverticulitis."
"With colonic release, we are seeking to peel apart the two components
of the linaclotide mechanism of action, which we believe may lead to two
product opportunities potentially addressing multiple unmet
gastrointestinal needs," said Mark Currie, Ph.D., chief scientific
officer and president of research and development at Ironwood. "The
colonic release program is one of many efforts by Allergan and Ironwood
to tap into linaclotide's rich and pioneering pharmacology as we work
together to address the broad spectrum of GI patients' symptoms."
The randomized, double-blind, placebo-controlled, multi-site Phase IIb
clinical trial is expected to enroll up to 520 adult patients with
IBS-C. Patients will be randomized to one of eight groups: one group
receives placebo, one group receives 290 mcg linaclotide (approved
formulation), three groups receive various doses of CR1 (colonic release
formulation 1 at 30 mcg, 100 mcg or 300 mcg), and three groups receive
various doses of CR2 (colonic release formulation 2 at 30 mcg, 100 mcg
or 300 mcg). The 290 mcg approved formulation is included as a positive
control for this study. All doses will be administered orally, once
daily for 12 weeks. The trial is designed to assess the safety and
efficacy of each linaclotide colonic release dose and formulation,
including its effect on abdominal pain relief and complete spontaneous
bowel movement (CSBM) frequency, as well as on other abdominal and bowel
symptoms commonly experienced by IBS-C patients. The trial also aims to
evaluate how the two colonic release formulations compare to each other
and to the approved 290 mcg formulation of linaclotide, with the goal of
identifying appropriate doses and formulations for Phase III clinical
trials.
About Irritable Bowel Syndrome with Constipation
Irritable bowel syndrome with constipation (IBS-C) is a functional
gastrointestinal disorder in which individuals experience hallmark
symptoms of abdominal pain and infrequent bowel movements (less than
three times per week). While estimates vary, as many as 13 million
adults in the U.S. may suffer from IBS-C. Results derived from responses
to a web based survey commissioned by Forest Pharmaceuticals and
Ironwood Pharmaceuticals suggest that only about half of adult IBS-C
sufferers are medically diagnosed. There are few available prescription
treatment options for this condition.
About Linaclotide
Linaclotide is a guanylate cyclase‐C (GC‐C) agonist that is thought to
work in two ways based on nonclinical studies. Linaclotide binds to the
GC-C receptor locally, within the intestinal epithelium. Activation of
GC-C results in increased intestinal fluid secretion and accelerated
transit and a decrease in the activity of pain-sensing nerves in the
intestine. The clinical relevance of the effect on pain fibers, which is
based on nonclinical studies, has not been established. Linaclotide is
marketed by Ironwood and Allergan in the United States as LINZESS® and
is indicated for the treatment of adults with irritable bowel syndrome
with constipation (IBS-C) or chronic idiopathic constipation (CIC).
Linaclotide is marketed by Allergan for the treatment of adults with
moderate to severe IBS-C in Europe under the brand name CONSTELLA®.
Ironwood also has partnered with Astellas Pharma Inc. for development
and commercialization of linaclotide in Japan and with AstraZeneca for
development and commercialization in China.
LINZESS and CONSTELLA are trademarks owned by Ironwood Pharmaceuticals,
Inc. Any other trademarks referred to in this press release are the
property of their respective owners. All rights reserved.
Important Safety Information
|
WARNING: PEDIATRIC RISK
|
LINZESS is contraindicated in pediatric patients under 6 years
of age. In nonclinical studies, administration of a single,
clinically relevant adult oral dose of linaclotide caused deaths
due to dehydration in young juvenile mice. Use of LINZESS should
be avoided in pediatric patients 6 through 17 years of age. The
safety and efficacy of LINZESS has not been established in
pediatric patients under 18 years of age.
|
Contraindications
-
LINZESS is contraindicated in pediatric patients under 6 years of age.
-
LINZESS is contraindicated in patients with known or suspected
mechanical gastrointestinal obstruction.
Warnings and Precautions
Pediatric Risk
-
LINZESS is contraindicated in children under 6 years of age. The
safety and effectiveness of LINZESS in pediatric patients under 18
years of age have not been established. In neonatal mice, increased
fluid secretion as a consequence of GC-C agonism resulted in mortality
within the first 24 hours due to dehydration. Due to increased
intestinal expression of GC-C, children under 6 years of age may be
more likely than older children and adults to develop significant
diarrhea and its potentially serious consequences.
-
Use of LINZESS should be avoided in pediatric patients 6 through 17
years of age. Although there were no deaths in older juvenile mice,
given the deaths in young juvenile mice and the lack of clinical
safety and efficacy data in pediatric patients, use of LINZESS should
be avoided in pediatric patients 6 through 17 years of age.
Diarrhea
-
Diarrhea was the most common adverse reaction of LINZESS-treated
patients in the pooled IBS-C and CIC double-blind placebo-controlled
trials. Severe diarrhea was reported in 2% of LINZESS-treated
patients. The incidence of diarrhea was similar in the IBS-C and CIC
populations.
-
Patients should be instructed to stop LINZESS if severe diarrhea
occurs and to contact their healthcare provider. The healthcare
provider should consider dose suspension and rehydration.
Adverse Reactions
-
In IBS-C clinical trials, the most common adverse reactions in
LINZESS-treated patients (incidence ≥2% and greater than placebo) were
diarrhea (20% vs 3% placebo), abdominal pain (7% vs 5%), flatulence
(4% vs 2%), headache (4% vs 3%), viral gastroenteritis (3% vs 1%) and
abdominal distension (2% vs 1%).
-
In CIC clinical trials, the most common adverse reactions in
LINZESS-treated patients (incidence ≥2% and greater than placebo) were
diarrhea (16% vs 5% placebo), abdominal pain (7% vs 6%), flatulence
(6% vs 5%), upper respiratory tract infection (5% vs 4%), sinusitis
(3% vs 2%) and abdominal distension (3% vs 2%).
Please see full Prescribing Information including Boxed Warning: http://www.frx.com/pi/linzess_pi.pdf
About Allergan
Allergan plc (NYSE: AGN), headquartered in Dublin, Ireland, is a unique,
global pharmaceutical company and a leader in a new industry model -
Growth Pharma. Allergan is focused on developing, manufacturing and
commercializing innovative branded pharmaceuticals, high-quality generic
and over-the-counter medicines and biologic products for patients around
the world.
Allergan markets a portfolio of best-in-class products that provide
valuable treatments for the central nervous system, eye care, medical
aesthetics, gastroenterology, women's health, urology, cardiovascular
and anti-infective therapeutic categories, and operates the world's
third-largest global generics business, providing patients around the
globe with increased access to affordable, high-quality
medicines. Allergan is an industry leader in research and development,
with one of the broadest development pipelines in the pharmaceutical
industry and a leading position in the submission of generic product
applications globally.
With commercial operations in approximately 100 countries, Allergan is
committed to working with physicians, healthcare providers and patients
to deliver innovative and meaningful treatments that help people around
the world live longer, healthier lives.
For more information, visit Allergan's website at www.allergan.com.
About Ironwood Pharmaceuticals
Ironwood Pharmaceuticals (NASDAQ: IRWD) is focused on creating medicines
that make a difference for patients, building value to earn the
continued support of our fellow shareholders, and empowering our team to
passionately pursue excellence. We discovered, developed and are
commercializing linaclotide, which is approved in the United States and
a number of other countries. Our pipeline priorities include exploring
further opportunities for linaclotide, as well as leveraging our
therapeutic expertise in gastrointestinal disorders and our
pharmacologic expertise in guanylate cyclases to address patient needs
across the upper and lower gastrointestinal tract. Ironwood was founded
in 1998 and is headquartered in Cambridge, Mass. Connect with us at www.ironwoodpharma.com
or on Twitter at www.twitter.com/ironwoodpharma;
information that may be important to investors will be routinely posted
in both these locations.
Statements contained in this press release that refer to future
events or other non-historical facts are forward-looking statements that
reflect the current perspective of Allergan or Ironwood on existing
trends and information as of the date of this release. Except as
expressly required by law, Allergan and Ironwood disclaim any intent or
obligation to update these forward-looking statements. Actual results
may differ materially from the current expectations of Allergan or
Ironwood depending upon a number of factors affecting the business of
each company. These factors include, among others, the risk that we are
unable to complete the Phase IIb clinical study for linaclotide colonic
release on the same timeline as we currently anticipate or are otherwise
unable to effectively execute on our clinical program for linaclotide
colonic release; the risk that the data from such clinical study are not
available when we currently anticipate them or do not demonstrate the
results we expect, including with respect to efficacy, safety or
difference between the two formulations; the risk that the clinical
study needs to be discontinued for any reason, including safety,
tolerability, enrollment, manufacturing or economic reasons; those
related to decisions made by regulatory authorities; those risks related
to competition and future business decisions made by us and our
competitors or potential competitors; and other risks and uncertainties
detailed in the periodic public filings with the Securities and Exchange
Commission by both Allergan and Ironwood, including but not limited to
each company's Quarterly Report on Form 10-Q for the quarter ended June
30, 2015 (for Allergan, such periodic public filings having been filed
under the "Allergan plc" or "Actavis plc" names) and from time to time
in each company's other investor communications. Except as expressly
required by law, Allergan and Ironwood disclaim any intent or obligation
to update these forward-looking statements.
View source version on businesswire.com: http://www.businesswire.com/news/home/20151102005260/en/
Allergan plc
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Mark Marmur, 973-906-1526
or
Investor
Relations:
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-or-
Ironwood
Pharmaceuticals, Inc.
Media Relations:
Trista Morrison,
617-374-5095
tmorrison@ironwoodpharma.com
or
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Relations:
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mkaya@ironwoodpharma.com
Source: Ironwood Pharmaceuticals, Inc.
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