Ironwood Pharmaceuticals and Forest Laboratories Announce Presentation of Linaclotide...

Ironwood Pharmaceuticals and Forest Laboratories Announce Presentation of
Linaclotide Phase 2b Chronic Constipation Study Results
- Data being presented today at Digestive Disease Week -

CAMBRIDGE, Mass. and NEW YORK, May 20 /PRNewswire-FirstCall/ -- Ironwood
Pharmaceuticals, Inc. (formerly Microbia, Inc.) and Forest Laboratories, Inc.
(NYSE: FRX) today announced the presentation of data from a Phase 2b
randomized, double-blind, placebo-controlled study assessing the safety and
efficacy of linaclotide in patients with chronic constipation (CC). Analysis
of these data indicate that linaclotide met its primary endpoint. The study
results are being presented today at the Digestive Disease Week conference in
San Diego by Anthony Lembo, M.D. of the Beth Israel Deaconess Medical Center
in Boston.
(Logo: http://www.newscom.com/cgi-bin/prnh/20001011/FORESTLOGO )
In the four-week study, once-daily doses of linaclotide -- 75 mcg, 150
mcg, 300 mcg, or 600 mcg -- were compared to placebo. The primary endpoint was
the change from pre-treatment in weekly spontaneous bowel movement (SBM)
frequency. During the two-week pre-treatment period, the mean baseline weekly
SBM frequency rate for the intent-to-treat (ITT) population (n = 307) across
all treatment groups was 2.3. Patients in the ITT population who received
once-daily dosing of linaclotide demonstrated a statistically significant
change in weekly SBM frequency of 2.6 (75 mcg, p < 0.05), 3.3 (150 mcg,
p < 0.01), 3.6 (300 mcg, p < 0.001), and 4.3 (600 mcg, p < 0.001) compared to
1.5 for patients receiving placebo. Increases in SBM frequency were
dose-related. At all doses above 75 mcg, linaclotide-treated patients also
experienced statistically significant improvements in complete spontaneous
bowel movement (CSBM) frequency, stool consistency, straining, bloating,
abdominal discomfort, and severity of constipation. Linaclotide was well
tolerated at all doses with no treatment-related serious adverse events in any
patient during the treatment period. The most common adverse event was
diarrhea, which occurred in 5 percent (75 mcg), 9 percent (150 mcg), 5 percent
(300 mcg), and 14 percent (600 mcg) of linaclotide-treated patients compared
to 3 percent of placebo-treated patients. Diarrhea resulted in the
discontinuation of 3 percent of linaclotide-treated patients and none of the
placebo-treated patients.
"Chronic constipation is an uncomfortable condition that can adversely
affect a patient's quality of life," said Anthony Lembo, M.D. "These Phase 2b
data indicate that linaclotide has the potential to significantly improve the
symptoms associated with CC."
This study is part of a larger Phase 2 program investigating the effect of
linaclotide treatment on patients with CC and irritable bowel syndrome with
constipation (IBS-C). Ironwood and Forest previously announced the top-line
interim analysis from the IBS-C study. The companies intend to present the
Phase 2B IBS-C study data at an appropriate scientific venue later this year.
The companies plan to initiate Phase 3 trials in both IBS-C and CC patients in
the second half of 2008.
CC Trial Design
The U.S.-based Phase 2b study was designed to assess the safety, efficacy,
and dose response of linaclotide in patients with CC. The primary efficacy
endpoint was the change in the overall mean weekly frequency of SBMs from the
pre-treatment baseline through the four-week treatment period. Following a
no-drug washout period of 14-17 days, patients (n = 310, with equal
randomization across treatment groups) were randomized to receive placebo or
linaclotide once-daily in the morning at doses of 75 mcg, 150 mcg, 300 mcg or
600 mcg for 28 days. Following completion of the four weeks of double-blind
treatment, patients were followed up for safety assessments for an additional
two weeks. Bowel function measurements included the number of SBMs and CSBMs
compared to baseline, stool consistency using the Bristol Stool Form Scale
(BSFS), and straining. Patient-reported outcomes included measures of
abdominal pain, abdominal discomfort, and bloating on a daily basis, and
constipation severity and overall relief of constipation on a weekly basis. In
addition, the use of rescue medication, end-of-treatment satisfaction, and
disease-specific quality of life were assessed.
Glossary of Terms
Spontaneous bowel movement (SBM): An SBM is a bowel movement that occurs
in the absence of laxative, enema, or suppository usage within the preceding
24 hours.
Complete spontaneous bowel movement (CSBM): A CSBM is an SBM that is
accompanied by the patient self-reporting a feeling of complete evacuation.
Bristol Stool Form Scale (BSFS): A seven-point scale measuring stool
consistency. BSFS is a surrogate marker of gastrointestinal transit time.
About Linaclotide
Linaclotide is a first-in-class compound currently being evaluated for the
treatment of IBS-C, CC, and other gastrointestinal disorders. Linaclotide is
an agonist of guanylate cyclase type-C, a receptor found on the lining of the
intestine. In preclinical testing linaclotide was shown to decrease visceral
pain, increase fluid secretion into the intestine, and accelerate intestinal
transit. Linaclotide was designed to exert its effect on the intestine with
minimal systemic exposure. In Phase 2a trials, linaclotide improved bowel
function as measured by both CSBMs and SBMs in patients with CC and IBS-C. An
issued composition of matter patent for linaclotide provides protection to
2025. In September 2007, Ironwood and Forest entered into a 50/50
collaboration to co-develop and co-promote linaclotide in United States.
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 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. Health care costs associated with
IBS exceed $25 billion annually. IBS patients fall into three subgroups --
constipation-predominant (IBS-C), diarrhea-predominant (IBS-D), and
alternating (IBS-A) -- and 30% to 40% 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 Digestive Disease Week (DDW)
DDW is the largest international gathering of physicians, researchers, and
academics in the fields of gastroenterology, hepatology, endoscopy, and
gastrointestinal surgery. Jointly sponsored by the American Association for
the Study of Liver Diseases, the American Gastroenterological Association
(AGA) Institute, the American Society for Gastrointestinal Endoscopy, and the
Society for Surgery of the Alimentary Tract, DDW takes place May 17-22, 2008,
at the San Diego Convention Center, San Diego, CA. The meeting showcases
approximately 5,000 abstracts and hundreds of lectures on the latest advances
in GI research, medicine and technology. For more information, visit
http://www.ddw.org.
About Ironwood Pharmaceuticals
Ironwood Pharmaceuticals (formerly Microbia)
(http://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, Inc., is an industrial biotechnology company developing and
commercializing novel bioprocesses for the production of specialty chemicals.
Ironwood has raised $231 million in private equity financing and is located in
Cambridge, Massachusetts.
About Forest Laboratories Inc. and Its Products
Forest Laboratories is a U.S.-based pharmaceutical company dedicated to
identifying, developing, and delivering products that make a positive
difference in people's lives. Forest Laboratories' growing product line
includes Lexapro(R) (escitalopram oxalate), an SSRI indicated for adults for
the initial and maintenance treatment of major depressive disorder and
generalized anxiety disorder; Namenda(R) (memantine HCl), an
N-methyl-D-aspartate (NMDA)-receptor antagonist indicated for the treatment of
moderate to severe Alzheimer's disease; Campral(R)* (acamprosate calcium),
indicated in combination with psychosocial support for the maintenance of
abstinence from alcohol in patients with alcohol dependence who are abstinent
at treatment initiation; and Bystolic(R) (nebivolol), a beta-adrenergic
receptor blocking agent indicated for the treatment of hypertension. For more
information, visit http://www.frx.com.
*Campral is a registered trademark of Merck Sante s.a.s., a subsidiary of
Merck KGaA, Darmstadt, Germany.
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

Susan Brady, Corporate Communications, Ironwood Pharmaceuticals,
+1-617-621-8304, sbrady@ironwoodpharma.com; or Charles E. Triano, Vice
President, Investor Relations, Forest Laboratories, +1-212-224-6714,
charles.triano@frx.com