BARCELONA & CAMBRIDGE, Mass., Nov 01, 2010 (BUSINESS WIRE) -- Almirall, S.A. (ALM:MC) and Ironwood Pharmaceuticals, Inc. (NASDAQ:
IRWD) today announced positive top-line results from a 26-week pivotal
Phase 3 clinical trial assessing the efficacy and safety of once-daily
dosing of linaclotide 266 mcg in patients with irritable bowel syndrome
with constipation (IBS-C).
The two co-primary endpoints required by the European Medicines Agency
(EMA) were met in this trial, showing statistically significant
improvements for linaclotide-treated patients for both abdominal
pain/abdominal discomfort responder (p<0.0001) and IBS degree of relief
responder (p<0.0001) over the first 12 weeks. Significant improvement
was also achieved for all secondary efficacy endpoints (p<0.0001)
including 26-week abdominal pain/abdominal discomfort responder, 26-week
IBS degree of relief responder, and change from baseline in 12-week
stool frequency, stool consistency, straining, and bloating. The
incidence of adverse events was similar to that observed in the previous
Phase 3 trial of linaclotide in patients with IBS-C, with diarrhea being
the most common adverse event in linaclotide-treated patients.
"These very positive results represent a significant milestone in the
Phase 3 clinical trial program for linaclotide which has been developed
specifically to provide long term relief from the symptoms of irritable
bowel syndrome with constipation, an area in which a very high unmet
need exists," said Per Olof Andersson, Chief Scientific Officer,
Almirall.
"We continue to see that linaclotide significantly improves abdominal
pain and constipation symptoms. The results of these Phase 3 data show
that patients with IBS-C experienced sustained improvement of their
symptoms over 26 weeks," said Mark Currie, Ph.D, Chief Scientific
Officer, Ironwood. "We are looking forward to the opportunity to bring
this treatment to the millions of patients suffering from IBS-C
globally."
This trial, MCP-103-302, conducted in North America jointly by Ironwood
and its U.S. partner Forest Laboratories, Inc., was designed to support
regulatory submission for linaclotide in both Europe and the U.S. In a
separate press release issued today, Ironwood and Forest announced
positive top-line results from this trial for the U.S. endpoints.
Ironwood has out-licensed linaclotide to Almirall for European
development and commercialization. Regulatory filing in Europe is
expected in the second half of 2011. The companies expect to present
detailed results of the two Phase 3 trials at appropriate scientific
conferences.
Phase 3 Trial MCP-103-302
Primary Efficacy Endpoint Results
Trial MCP-103-302 was a multicenter, randomized, double-blind,
placebo-controlled trial conducted in 805 patients meeting modified Rome
II criteria for IBS-C. The trial included a two-week pre-treatment
baseline period and a 26-week treatment period, with patients receiving
either a once-daily dose of linaclotide 266 mcg or placebo. 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 87 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 (54.1 percent vs. 38.5 percent, p<0.0001) 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 first 12 weeks of the 26-week 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 (39.4 percent vs. 16.6 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 first 12 weeks of the 26-week treatment period.
Main Secondary Endpoints
All main secondary endpoints measured in MCP-103-302 were statistically
significant (p<0.0001) for linaclotide-treated patients compared to
placebo-treated patients: 26-week abdominal pain/ abdominal discomfort
responder (53.6 percent vs. 36.0 percent), 26-week IBS degree of relief
responder (37.2 percent vs. 16.9 percent), and changes from baseline
over 12 weeks in stool frequency, stool consistency, straining, and
bloating.
Adverse Events
The most common adverse events that occurred more frequently in
linaclotide-treated patients compared to placebo-treated patients were
diarrhea (19.7 percent vs. 2.5 percent), abdominal pain (4.5 percent vs.
4.0 percent), flatulence (3.7 percent vs. 2.2 percent), viral
gastroenteritis (3.7 percent vs. 2.2 percent), and headache (3.2 percent
vs. 2.7 percent). Overall rates of discontinuation due to adverse events
were 10.2 percent for linaclotide-treated patients and 2.5 percent for
placebo-treated patients; 4.5 percent of linaclotide-treated patients
discontinued due to diarrhea compared with 0.2 percent of
placebo-treated patients.
About Almirall
Almirall is an international pharmaceutical company based on innovation
and committed to health. Headquartered in Barcelona, Spain, it
researches, develops, manufactures and commercializes its own R&D and
licensed drugs with the aim of improving people's health and wellbeing.
Almirall focuses its research resources on 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) 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. For
further information, please visit www.ironwoodpharma.com.
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, 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 successful completion of our long-term safety
studies, our ability to produce an adequate commercial supply of
linaclotide, the timing of the filing of a Marketing Authorization
Application for linaclotide, and the potential size of linaclotide's
target patient population. 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 the risks that our other linaclotide
development activities do not progress as expected, serious adverse
events arise in patients that are deemed to be definitely or probably
related to linaclotide treatment, the incidence or severity of diarrhea
in patients treated with linaclotide is higher than expected, and we are
unable to produce an adequate commercial supply of linaclotide, as well
as risks related to the difficulty of predicting regulatory approvals,
the acceptance of and demand for new pharmaceutical products, the impact
of competitive products and pricing, and whether linaclotide will ever
be commercialized successfully. Applicable risks also include those that
are listed in our Quarterly Report on Form 10-Q for the three months
ended June 30, 2010, in addition to 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 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, an 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 will co-promote 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
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 quality of life,
accompanied by considerable socio-economic and psychological consequences1-4,
and represents a major proportion of gastrointestinal workload in both
primary and secondary care5. The overall prevalence is 11.5
percent (6.2 percent-12 percent); 9.6 percent have current symptoms, 4.8
percent have been formally diagnosed, with 16-34% of these patients
experiencing the constipation-predominant form of the condition 6.
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 the Prior Phase 3 Trial
Results communicated in this release are consistent with those from a
prior Phase 3 trial assessing linaclotide's safety and efficacy in
patients with IBS-C. Positive top-line results from the Phase 3 clinical
trial LIN-MD-31, which involved 803 patients and assessed the efficacy
and safety of a once-daily dosing of linaclotide 266 mcg in patients
with irritable bowel syndrome with constipation, was announced in
September 2010.
References
1. Talley NJ, Gabriel SE, Harmsen WS, et al. Medical costs in community
subjects with irritable bowel syndrome. Gastroenterology 1995; 109:
1732-41.
2. Longstreth GF. Irritable Bowel Syndrome -- a multibillion dollar
problem. Gastroenterology 1995; 109: 2029-31.
3. Whitehead WE, Burnett CK, Cook EW III, Taub E. Impact of Irritable
Bowel Syndrome on quality of life. Digestive Dis Sci 1996; 41: 2248-53.
4. Jones RH. Clinical economics review -- gastrointestinal disease in
primary care. Aliment Pharmacol Ther 1996; 10: 233-9.
5. Thompson WG, Heaton KW, Smyth GT, Smyth C. Irritable bowel syndrome
in general practice: prevalence, characteristics and referral. Gut 2000;
46: 77-8.
6. P. S. Hungin et al - The prevalence, patterns and impact of irritable
bowel syndrome: an international survey of 40,000 subjects - Aliment
Pharmacol Ther 2003; 17: 643-650.
7. Almirall and Ironwood announce positive results from a Phase 3 trial
with linaclotide in patients with irritable bowel syndrome with
constipation 14th September 2010 - http://www.almirall.com/webcorp2/cda/comunicacion_detalle_noticia.jsp?id=1409.
SOURCE: Almirall, S.A. and Ironwood Pharmaceuticals, Inc.
Ironwood Contact:
Ironwood Pharmaceuticals, Inc.
Susan Brady, 617-621-8304
Corporate Communications
sbrady@ironwoodpharma.com
or
Almirall Contact (journalists):
Ketchum Pleon
Amanda Sefton, +44 (0) 207.611.3653
amanda.sefton@ketchumpleon.com
or
Investors (for investors and analysts only):
Jordi Molina, +34 93 291 3087
jordi.molina@almirall.com
Copyright Business Wire 2010