- Data Presented Today at ACG Annual Scientific Meeting - ORLANDO, Fla., Oct. 7
ORLANDO, Fla., Oct. 7 /PRNewswire-FirstCall/ -- Ironwood Pharmaceuticals,
Inc. (formerly Microbia, Inc.) and Forest Laboratories, Inc. (NYSE: FRX) today
announced the presentation of results 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 indicates 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. Further, the safety
and tolerability profile support advancing this novel compound into Phase 3
clinical trials. The study results were presented today in a plenary session
at the American College of Gastroenterology (ACG) 2008 Annual Scientific
Meeting in Orlando, Fla.
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"Patients with IBS-C are in need of effective and well tolerated
therapies. The results of this study showing improvement in abdominal pain and
constipation are encouraging," said Douglas Drossman, M.D., Professor of
Medicine and Psychiatry at UNC School of Medicine, Division of
Gastroenterology and Hepatology and Co-Director of the UNC Center for
Functional GI & Motility Disorders, University of North Carolina at Chapel
Hill, N.C.
Study Results
420 patients were randomized into the study and 337 completed the 12-week
treatment period. At all linaclotide dose levels, the change from baseline vs.
placebo for complete spontaneous bowel movement (CSBM) frequency-the study's
primary endpoint-was clinically and statistically significant (2.5 to 3.6 vs.
1.0; p = 0.0036 to <0.0001). In addition, abdominal pain was clinically and
statistically significantly reduced in all linaclotide treatment groups
compared to placebo (-0.7 to -0.9 change from baseline on a 5-point ordinal
severity scale vs. -0.5; p = 0.0239 to <0.0001) and, in the 26 percent of
patients with severe/very severe baseline abdominal pain, improvement was even
more pronounced (-0.8 to -1.3 v -0.2; p = 0.0236 to <0.0001). Results for
spontaneous bowel movement (SBM) frequency, stool consistency, straining,
abdominal discomfort, bloating, IBS symptom severity, and global assessments
were statistically significant for the 300 ug and 600 ug dose groups and for
at least one of the two lower doses for each endpoint. Treatment effects of
linaclotide were rapid in onset (within the first week of treatment) and were
maintained throughout the entire 12-week treatment period; there was no
indication of rebound clinical effects following cessation of treatment.
Linaclotide was well tolerated at all doses with no treatment-related serious
adverse events. The most common adverse event was diarrhea; however, there
were no associated dehydration or electrolyte abnormalities. Diarrhea resulted
in the discontinuation of 1 percent to 7 percent of linaclotide-treated
patients and none of the placebo-treated patients.
This study was part of a larger Phase 2 program investigating the effect
of linaclotide treatment on patients with IBS-C or chronic constipation (CC).
Ironwood and Forest previously announced the results from the Phase 2b CC
study and have initiated two pivotal Phase 3 CC trials and expect to initiate
two pivotal Phase 3 IBS-C trials by January 2009.
IBS-C Phase 2b Study Design
This North American-based, randomized, multi-center, double-blind,
placebo-controlled, dose-range-finding, parallel-group Phase 2b study was
designed to assess the safety, efficacy, and dose response of linaclotide in
patients with IBS-C. The primary efficacy endpoint was change from baseline in
CSBM frequency. The study evaluated the effects of 75, 150, 300 or 600 ug
linaclotide or placebo administered orally once daily to adults meeting
modified Rome II criteria for IBS-C. Participants underwent two-week-baseline,
12-week-treatment, and two-week-post-treatment evaluations with daily
assessments of bowel habits and symptom severity, and weekly global
assessments using an interactive voice response system. During the baseline
period patients had to demonstrate <3 CSBM/week and mean daily abdominal pain
of at least mild severity. Treatment effects in the intent-to-treat population
were estimated using an analysis of covariance and the Cochran-Mantel Haenszel
test.
About Linaclotide
Linaclotide is a first-in-class compound currently being evaluated for the
treatment of IBS-C, CC, and other gastrointestinal disorders. Linaclotide was
designed to exert its effect on the intestine with minimal systemic exposure.
Linaclotide is an agonist of guanylate cyclase type-C, a receptor found on the
lining of the intestine. Linaclotide demonstrated proof of concept in a
comprehensive Phase 2b program, comprised of two clinical studies in over 700
patients with either IBS-C or CC. In patients with IBS-C, linaclotide reduced
abdominal pain and relieved constipation-the hallmarks of the condition-
throughout the 12-week treatment period. In patients with CC, linaclotide
reduced constipation throughout the 4-week study period. Linaclotide was well
tolerated at all doses in both Phase 2b studies, with the most common adverse
event being diarrhea. A United States patent covering linaclotide composition
of matter expires in 2025. In September 2007, Ironwood and Forest Laboratories
entered into a 50/50 collaboration to co-develop and co-promote linaclotide in
the United States. Ironwood retains exclusive rights to linaclotide outside of
North America.
About Irritable Bowel Syndrome (IBS)
One out of six adults in developed countries suffers from IBS, a chronic
condition marked by abdominal pain and disturbed bowel function. IBS accounts
for 12% of adult visits to primary care physicians and is the most common
disorder diagnosed by gastroenterologists. Healthcare costs associated with
IBS exceed $25 billion annually. IBS patients fall largely into three
subgroups-constipation-predominant (IBS-C), diarrhea-predominant (IBS-D), and
mixed IBS (IBS-M)-and 30 percent to 40 percent of these patients suffer from
IBS-C. There are currently few available therapies to treat the nine million
U.S. patients diagnosed with IBS-C.
About Chronic Constipation (CC)
As many as 26 million Americans suffer from CC. Patients with CC often
experience hard and lumpy stools, straining during defecation, a sensation of
incomplete evacuation, and fewer than three bowel movements per week. The
discomfort of CC significantly affects patients' quality of life by impairing
their ability to work and participate in typical daily activities.
About Ironwood Pharmaceuticals
Ironwood Pharmaceuticals (formerly Microbia) (www.ironwoodpharma.com) is
an entrepreneurial pharmaceutical company dedicated to the science and art of
great drugmaking. The Company is advancing several clinical
candidates-linaclotide for the treatment of irritable bowel syndrome with
constipation, chronic constipation, and other functional gastrointestinal
disorders; and novel, next-generation cholesterol absorption inhibitors for
the treatment of hypercholesterolemia. Ironwood also has a growing pipeline of
additional drug candidates in earlier stages of development. Microbia
Precision Engineering, Inc., a majority-owned subsidiary of Ironwood, is an
industrial biotechnology company developing and commercializing novel
bioprocesses for the production of specialty chemicals. Ironwood has raised
$281 million in private equity financing and is located in Cambridge,
Massachusetts.
About Forest Laboratories Inc. and Its Products
Forest Laboratories (NYSE: FRX) is a US-based pharmaceutical company with
a long track record of building partnerships and developing and marketing
products that make a positive difference in people's lives. In addition to its
well-established franchises in therapeutic areas of the central nervous and
cardiovascular systems, Forest's current pipeline includes product candidates
in all stages of development and across a wide range of therapeutic areas. The
company is headquartered in New York, NY. To learn more about Forest
Laboratories, visit www.FRX.com.
Except for the historical information contained herein, this release
contains forward-looking statements within the meaning of the Private
Securities Litigation Reform Act of 1995. These statements involve a number of
risks and uncertainties, including the difficulty of predicting FDA approvals,
the acceptance and demand for new pharmaceutical products, the impact of
competitive products and pricing, the timely development and launch of new
products, and the risk factors listed from time to time in Forest
Laboratories' Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and
any subsequent SEC filings.
SOURCE Forest Laboratories, Inc.; Ironwood Pharmaceuticals
