- 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
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Related links:
http://www.frx.com
http://www.ironwoodpharma.com http://www.ddw.org
Photo Notes:
NewsCom: http://www.newscom.com/cgi-bin/prnh/20001011/FORESTLOGO
AP Archive: http://photoarchive.ap.org
PRN Photo Desk, photodesk@prnewswire.com
CONTACT:
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
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