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Top-line results of the phase 3 study with linaclotide show that both
primary and main secondary endpoints were met and was well tolerated.
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Irritable bowel syndrome with constipation (IBS-C) is a dehabilitating
disease that impacts patient's quality of life.
IRWDNewsThe two co-primary endpoints required by the European Medicines Agency
(EMA) were met in this study, showing statistical significance and
clinically relevant improvement for linaclotide-treated patients both
for abdominal pain/abdominal discomfort responder and IBS degree of
relief responder over the three-month period. Significant improvement
was also achieved for all pre-specified main secondary endpoints (stool
frequency, stool consistency, straining, and bloating). The safety
results were consistent with those observed in previous linaclotide
clinical trials, with diarrhea being the most common adverse event in
linaclotide-treated patients.
"IBS is a disease that severely impacts the quality of life of patients
and linaclotide is a specific treatment developed for the relief of
symptoms in this condition," said Per Olof Andersson, Executive Director
R&D, Almirall. "These results are very promising and we believe
linaclotide will be a valuable treatment in an area with such high unmet
need. We look forward to the results of the second pivotal trial in Q4
2010 led by our partner Ironwood."
"The results of this Phase 3 trial, combined with previously reported
positive linaclotide trial results, further support our belief that
linaclotide has the potential to improve abdominal pain and bowel
symptoms, offering a promising treatment for individuals suffering from
this chronic gastrointestinal disorder," said Peter Hecht, Chief
Executive Officer of Ironwood.
LIN-MD-31, conducted in North America jointly by Ironwood and their U.S.
partner Forest Laboratories, Inc., was designed to support regulatory
submission in both Europe and the U.S. In a separate press release
today, Ironwood and Forest announce positive top-line results from this
trial for the U.S. endpoints. The trial is part of a larger Phase 3
program investigating the effect of linaclotide treatment on patients
with IBS-C. The companies expect the top-line results of the second
Phase 3 trial to be available in Q4 2010, after which filing dates in
Europe will be determined.
Ironwood has out-licensed linaclotide to Almirall for European
development and commercialization. The companies expect to present
detailed results of the studies at appropriate scientific conferences.
Phase 3 trial LIN-MD-31
Primary Efficacy Endpoint Results
Trial LIN-MD-31 was a multicenter, randomized, double-blind,
placebo-controlled trial conducted in 803 patients meeting modified Rome
II criteria for IBS-C. The trial included a two-week pre-treatment
baseline period, a 12-week treatment period with patients receiving
either a 266 mcg dose of linaclotide or placebo, and a four-week
randomized withdrawal period. During the pre-treatment baseline period
the mean abdominal pain score was 5.6 (on a 0 10 scale where 0 is no
abdominal pain and 10 is very severe abdominal pain) with 88 percent of
patients suffering from abdominal pain every day. The results for the
co-primary endpoints are detailed below:
1. 12-week Abdominal Pain/Abdominal Discomfort Responder
A
greater proportion of linaclotide-treated patients compared to
placebo-treated patients (55 percent vs. 42 percent, p=0.0002) had an
improvement from baseline of 30 percent or more in either the mean
abdominal pain score or the mean abdominal discomfort score for at least
six of the 12 weeks of the treatment period, with neither of these
scores worsening from baseline for the same week.
2. 12-week IBS Degree of Relief Responder
A greater
proportion of linaclotide-treated patients compared to placebo-treated
patients (37 percent vs. 18 percent, p<0.0001) responded to the degree
of relief of IBS symptoms question with an answer of "considerably
relieved" or "completely relieved", for at least six of the 12 weeks of
the treatment period.
All main secondary endpoints measured in LIN-MD-31 (stool frequency,
stool consistency, straining and bloating) were statistically
significant (p<0.0001) for linaclotide-treated patients compared to
placebo-treated patients. There was no evidence of rebound worsening of
abdominal or bowel symptoms during the randomized withdrawal period.
The most common adverse events that occurred more frequently in
linaclotide-treated patients compared to placebo-treated patients were
diarrhoea (19 percent vs. 4 percent), flatulence (5 percent vs. 2
percent), abdominal pain (5 percent vs. 3 percent), and headache (5
percent vs. 4 percent). Overall rates of discontinuation due to adverse
events were 8 percent for linaclotide and 3 percent for placebo.
About Almirall
Almirall is an international pharmaceutical company based on innovation
and committed to health. Headquartered in Barcelona, Spain, Almirall
researches, develops, manufactures and commercialises its own R&D and
licensed drugs with the aim of improving people's health and wellbeing.
Almirall focuses its research resources in therapeutic areas related to
the treatment of asthma, COPD (Chronic Obstructive Pulmonary Disease),
rheumatoid arthritis, multiple sclerosis, psoriasis and other
dermatological conditions. Almirall's products are currently present in
over 70 countries while it has direct presence in Europe and Latin
America through 12 affiliates. For further information please visit the
website at: www.almirall.com.
About Ironwood Pharmaceuticals
Ironwood
Pharmaceuticals (NASDAQ: IRWD - News) is an entrepreneurial pharmaceutical
company dedicated to the art and science of great drugmaking.
Linaclotide, Ironwood's GC-C agonist, is being evaluated in a
confirmatory Phase 3 program for the treatment of irritable bowel
syndrome with constipation (IBS-C) and chronic constipation. Ironwood
also has a growing pipeline of additional drug candidates in earlier
stages of development. Ironwood is located in Cambridge, Mass. To learn
more about Ironwood Pharmaceuticals, visit www.ironwoodpharma.com.
This press release contains forward looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995. You are
hereby cautioned not to place undue reliance on these forward-looking
statements, including, but not limited to, our top-line assessment of
our Phase 3 IBS-C clinical trial data and its implications for the
future development of linaclotide, linaclotide's potential as a
treatment for IBS-C, the timing of our release of additional top-line
results from a second linaclotide Phase 3 IBS-C trial, and the timing of
the filing of a Marketing Authorization Application for linaclotide.
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, among others, the risks that our other
linaclotide development activities do not progress, the difficulty of
predicting regulatory approvals, the acceptance of and demand for new
pharmaceutical products, the impact of competitive products and pricing,
whether linaclotide will ever be commercialized successfully and the
risk factors that are listed from time to time in Ironwood
Pharmaceuticals' Annual Reports on Form 10-K, Quarterly Reports on Form
10-Q, and any subsequent SEC filings. We undertake no obligation and do
not intend to update these forward-looking statements to reflect events
or circumstances occurring after this press release. 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.
About Linaclotide
Linaclotide, a first in class investigational drug, is an agonist of the
guanylate cyclase type-C (GC-C) receptor located on the luminal surface
of the intestine. In preclinical models, linaclotide has been shown to
reduce visceral pain, increase fluid secretion, and accelerate
intestinal transit. The effects on secretion and transit are mediated
through cyclic guanosine monophosphate (cGMP), which is also believed to
modulate the activity of local nerves to reduce pain. Linaclotide is an
orally delivered peptide that acts locally in the gut with no measurable
systemic exposure at therapeutic doses and is intended for once-daily
administration. Linaclotide is in Phase 3 clinical development for the
treatment of irritable bowel syndrome with constipation (IBS-C) and
chronic constipation. An issued composition of matter patent for
linaclotide provides protection to 2025.
Ironwood and Forest are co-developing and co-promoting linaclotide in
the United States. Also, Ironwood has out-licensed linaclotide to
Almirall for European development and commercialization, and to Astellas
Pharma Inc. for development and commercialization in Japan, Indonesia,
Korea, the Philippines, Taiwan, and Thailand.
About Irritable Bowel Syndrome with Constipation (IBS-C)
Irritable bowel syndrome (IBS), a functional gastrointestinal disorder,
is a recognized complex symptom with abdominal pain and disturbed bowel
action. It leads to a substantial reduction in the quality of life,
accompanied by considerable socio-economic and psychological
consequences 1-4, and represents a major proportion of
gastrointestinal workload in both primary and secondary care5.
The overall prevalence was 11.5 percent (6.2 percent12 percent); 9.6
percent had current symptoms, 4.8 percent had been formally diagnosed6.
There are currently few available therapies to treat this disorder and
there is a high rate of dissatisfaction with available therapies.
Patients suffering from IBS-C can be affected physically,
psychologically, socially, and economically.
About prior Phase IIb trials
Results communicated in this release are consistent with those from a
Phase 2b study assessing linaclotide's safety and efficacy in 420
patients with irritable bowel syndrome with constipation (IBS-C).
Analysis of the data indicated that once-daily oral dosing of
linaclotide, across a range of doses, significantly reduced abdominal
pain and significantly improved constipation symptoms in patients with
IBS-C throughout the 12-week study period. Those results were presented
at the 16th United European Gastroenterology Week in October 2008.
For further information, please refer to Ironwood's press release of
March 4th, 2008.
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WG, Heaton KW, Smyth GT, Smyth C. Irritable bowel syndrome in general
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