CAMBRIDGE, Mass.--(BUSINESS WIRE)--
Ironwood
Pharmaceuticals, Inc. (NASDAQ: IRWD) announced today that the Phase
II clinical trial of linaclotide conducted in adults with opioid-induced
constipation (OIC) met its primary endpoint. The OIC clinical trial was
conducted jointly by Ironwood and a subsidiary of Allergan plc,
Ironwood's co-development and co-commercialization partner for
linaclotide in the United States.
"These top-line data demonstrate the positive effect of the guanylate
cyclase-C (GC-C) agonist, linaclotide, on bowel movement frequency and
other key endpoints in patients with OIC," said Dr. Michael Hall, senior
vice president, clinical development of Ironwood. "As a pioneer and a
recognized leader in GC-C agonists, we are committed to continued
innovation with linaclotide, and we are very pleased with the results of
this OIC trial."
Top-line data from the Phase II trial indicate that linaclotide-treated
patients showed statistically significant improvement for the
pre-specified primary endpoint: change from baseline in the 8-week
Spontaneous Bowel Movement (SBM) frequency rate (SBMs/week), during the
treatment period, for both doses tested, 145 mcg and 290 mcg, compared
to placebo-treated patients. Consistent with previous Phase III trials
of linaclotide in irritable bowel syndrome with constipation (IBS-C) and
chronic idiopathic constipation (CIC), the most common adverse event
reported in linaclotide-treated patients was diarrhea, with the majority
being characterized as mild in severity.
This randomized, double-blind, placebo-controlled, multi-site Phase II
clinical trial enrolled 254 adult patients with chronic, non-cancer pain
who had been receiving a stable dose of an opioid analgesic and suffered
from constipation, defined as fewer than three spontaneous bowel
movements (SBMs) per week. Patients were randomized to receive 145 mcg
of linaclotide, 290 mcg of linaclotide, or placebo for eight weeks.
Ironwood and Allergan will make a decision regarding advancement of the
OIC program following a review of results from the linaclotide colonic
release Phase IIb trial in adults with IBS-C and continued analysis of
the full commercial opportunity. The companies expect data from the
linaclotide colonic release Phase IIb trial in the second half of 2016.
Linaclotide is currently approved in the United States for the treatment
of adults with IBS-C or CIC. It is also approved for adults with IBS-C
or CIC in a number of other countries. Linaclotide is not currently
approved for the treatment of OIC.
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.
LINZESS 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 Opioid-Induced Constipation
Opioids are a commonly prescribed class of pain medications that may
reduce fluids and movement within the intestine, resulting in
constipation. It is estimated that more than 8 million people in the
United States suffer from opioid-induced constipation (OIC). Symptoms of
OIC may include reduced bowel movement frequency, straining, incomplete
evacuation and a sensation of bowel obstruction.
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.
This press release contains forward-looking statements. Investors are
cautioned not to place undue reliance on these forward-looking
statements, including, but not limited to, statements about the top-line
data from the Phase II clinical trial of linaclotide in adults with OIC
and the plans for further analysis; the design of the Phase II trial and
its impact on the results thereof; the development plans for linaclotide
in OIC, including decisions regarding advancement and the drivers and
timing thereof; Ironwood's plans for continued innovation with
linaclotide, including the linaclotide colonic release Phase IIb trial
in IBS-C and the timing of data from such trial; and OIC symptoms and
the causes of such symptoms, as well as prevalence and unmet need. Each
forward‐looking statement is subject to risks and uncertainties that
could cause actual results to differ materially from those expressed or
implied in such statement. Applicable risks and uncertainties include,
but are not limited to, the risk that Ironwood and Allergan are unable
to effectively or timely execute on a development plan for linaclotide
in OIC; the risk that unfavorable findings may arise from new clinical
data or additional analyses of existing clinical data; the risks related
to the development of our pipeline of GC-C agonists, including efficacy,
safety and tolerability; the risk that we are unable to complete the
Phase IIb clinical trial for linaclotide colonic release in IBS-C on the
same timeline as we currently anticipate or that the data from such
clinical trial are not available when we currently anticipate them or do
not demonstrate the results we expect; the risk that the OIC patient
population is not as presently estimated or that there is insufficient
commercial opportunity; and those risks related to competition and
future business decisions made by Ironwood, Allergan and their
competitors or potential competitors. Applicable risks also include
those that are listed under the heading "Risk Factors" and elsewhere in
Ironwood's Quarterly Report on Form 10-Q for the quarter ended September
30, 2015, in addition to the risk factors that are listed from time to
time in Ironwood's Annual Reports on Form 10‐K, Quarterly Reports on
Form 10‐Q and any other subsequent SEC filings. Ironwood undertakes no
obligation to update these forward-looking statements to reflect events
or circumstances occurring after this press release. Except as otherwise
noted, these forward-looking statements speak only as of the date of
this press release. All forward‐looking statements are qualified in
their entirety by this cautionary statement.
View source version on businesswire.com: http://www.businesswire.com/news/home/20151130005211/en/
Ironwood Pharmaceuticals, Inc.
Media Relations:
Trista
Morrison, 617-374-5095
[email protected]
or
Investor
Relations:
Meredith Kaya, 617-374-5082
[email protected]
Source: Ironwood Pharmaceuticals, Inc.
News Provided by Acquire Media